title: Effect of intensive vs standard statin therapy on endothelial progenitor cells and left ventricular function in patients with acute myocardial infarction: Statins for regeneration after acute myocardial infarction and PCI (STRAP) trial. Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events? Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: a randomized controlled trial. Early Statin Treatment in Patients With Acute Coronary Syndrome: Demonstration of the Beneficial Effect on Atherosclerotic Lesions by Serial Volumetric Intravascular Ultrasound Analysis During Half a Year After Coronary Event: The ESTABLISH Study Composite outcomes in randomized trials: greater precision but with greater uncertainty? Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. The MIRACL study. Effect of intensive statin therapy on regression of coronary atherosclerosis in patients with acute coronary syndrome: a multicenter randomized trial evaluated by volumetric intravascular ultrasound using pitavastatin versus atorvastatin (JAPAN-ACS [Japan assessment of pitavastatin and atorvastatin  The effect of early treatment by cerivastatin on the serum level of C-reactive protein, interleukin-6, and interleukin-8 in patients with unstable angina and non-Q-wave myocadial infarction Effect of early use of low-dose pravastatin on major adverse cardiac events in patients with acute myocardial infarction: the OACIS-LIPID Study. Effect of lipid-lowering therapy on early mortality after acute coronary syndromes: an observational study Effects of atorvastatin 80 mg daily early after onset of unstable angina pectoris or non-Q-wave myocardial infarction. Apolipoprotein E polymorphisms influence effect of pravastatin on survival after myocardial infarction in a Mediterranean population: the GISSI-Prevenzione study. Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial. EFFICACY AND SAFETY OF ATORVASTATIN DURING EARLY HOSPITALIZATION IN ELDERLY PATIENTS WITH UNSTABLE ANGINA Early use of pravastatin in patients with acute myocardial infarction undergoing coronary angioplasty. Intensive statin therapy for Chinese patients with coronary artery disease undergoing percutaneous coronary intervention (ISCAP study) Beneficial effects of pravastatin (+/-colestyramine/niacin) initiated immediately after a coronary event (the randomized Lipid-Coronary Artery Disease [L-CAD] Study). The impact of early administration of low-dose atorvastatin treatment on inflammatory process, in patients with unstable angina and low cholesterol level. Fluvastatin in the first-line therapy of acute coronary syndrome: results of the multicenter, randomized, double-blind, placebo-controlled trial (the FACS-trial) The beneficial effect of high loading dose of rosuvastatin before percutaneous coronary intervention in patients with acute coronary syndrome. Fluvastatin in the therapy of acute coronary syndrome: Rationale and design of a multicenter, randomized, double-blind, placebo-controlled trial (The FACS Trial)[ISRCTN81331696] Effect of fluvastatin on ischaemia following acute myocardial infarction: a randomized trial. Rapid immunomodulation by rosuvastatin in patients with acute coronary syndrome. Design and rationale of a study in Asia of atorvastatin pretreatment in patients undergoing percutaneous coronary intervention for non-ST elevation acute coronary syndromes. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. Benefits of early lipid-lowering intervention in high-risk patients: the lipid intervention strategies for coronary patients study. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. Early statin treatment prior to primary PCI for acute myocardial infarction: REPERATOR, a randomized placebo‐controlled pilot trial Early invasive versus selectively invasive management for acute coronary syndromes. Rationale and design of assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (the ALPS-AMI) study. Lipid levels after acute coronary syndromes. Atorvastatin pretreatment improves outcomes in patients with acute coronary syndromes undergoing early percutaneous coronary intervention: results of the ARMYDA-ACS randomized trial. Fluvastatin reduces the 4-year cardiac risk in patients with multivessel disease. Association of Statin Therapy with Outcomes of Acute Coronary Syndromes: The GRACE Study Rosuvastatin induces apoptosis in CD4+CD28null T cells in patients with acute coronary syndromes Effect of simvastatin on plasma interleukin-6 in patients with unstable angina. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The effect of statin therapy on ventricular late potentials in acute myocardial infarction. Effects of rosuvastatin and atorvastatin on the apolipoprotein B/apolipoprotein A-1 ratio in patients with an acute coronary syndrome: The CENTAURUS trial design. Full-dose atorvastatin versus conventional medical therapy after non-ST-elevation acute myocardial infarction in patients with advanced non-revascularisable coronary artery disease Comparison of lipid-modifying efficacy of rosuvastatin versus atorvastatin in patients with acute coronary syndrome (from the LUNAR study). Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Intensive-Dose Atorvastatin Regimen Halts Progression of Atherosclerotic Plaques in New-onset Unstable Angina With Borderline Vulnerable Plaque Lesions Pravastatin in acute ischaemic syndromes: results of a randomised placebo-controlled trial. The effect of early statin treatment on inflammation and cardiac events in acute coronary syndrome patients with low-density lipoprotein cholesterol Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS): rationale and design. Early atorvastatin therapy improves cardiac function in patients with acute myocardial infarction. Beneficial effects of the addition of fenofibrate to statin therapy in patients with acute coronary syndrome after percutaneous coronary interventions. Time course of serum lipids and apolipoproteins after acute myocardial infarction: modification by pravastatin. Atorvastatin modifies the protein profile of circulating human monocytes after an acute coronary syndrome. Intensive cholesterol lowering with statin improves the outcomes of percutaneous coronary intervention in patients with acute coronary syndrome. Effects of 4 weeks of atorvastatin administration on the antiinflammatory cytokine interleukin-10 in patients with unstable angina. Diabetes mellitus is a major negative determinant of coronary plaque regression during statin therapy in patients with acute coronary syndrome--serial intravascular ultrasound observations from the Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome Trial (the JAPAN-ACS Tria [Effects of atorvastatin, alone and in combination with probucol on endothelial function in patients with acute coronary syndrome]. Effects of early statin treatment on symptomatic heart failure and ischemic events after acute myocardial infarction in Japanese. A randomized, controlled trial of simvastatin versus rosuvastatin in patients with acute myocardial infarction: the Secondary Prevention of Acute Coronary Events – Reduction of Cholesterol to Key European Targets Trial Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. Effects of short-term anti-inflammatory therapy on endothelial function in patients with non-ST-segment elevation acute coronary syndrome. Effect of pravastatin compared with placebo initiated within 24 hours of onset of acute myocardial infarction or unstable angina: the Pravastatin in Acute Coronary Treatment (PACT) trial. Atorvastatin has an important acute anti-inflammatory effect in patients with acute coronary syndrome: results of a randomized, double-blind, placebo-controlled study. Systematic, immediate in-hospital initiation of lipid-lowering drugs during acute coronary events improves lipid control. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Early intensive statin treatment for six months improves long-term clinical outcomes in patients with acute coronary syndrome (Extended-ESTABLISH trial): a follow-up study.
abstract: BACKGROUND Intensive statin therapy can lower the risk of recurrence of major cardiac events in patients with acute coronary syndromes . This could be related to the ability of statins to increase levels of Endothelial Progenitor Cells ( EPCs ) , which were demonstrated to be favorably associated with a better prognosis and post-infa rct ion left ventricular remodeling in patients with ischemic heart disease . AIM OF THE STUDY First , to evaluate , in a r and omized clinical trial , the effect of an intensive vs a st and ard treatment with statins on EPC mobilization in patients undergoing a successful primary or rescue percutaneous coronary intervention ; secondary , to evaluate whether left ventricular remodeling could be influenced by statin therapy through EPC mobilization . METHODS Forty ST-segment elevation myocardial infa rct ion ( STEMI ) patients undergoing a successful primary or rescue PCI were r and omized to receive atorvastatin 80 mg immediately after the admission ( Intensive Treatment , IT ) or atorvastatin 20 mg from the day of the discharge ( St and ard Treatment , ST ) . CD34+/KDR+ EPC count by flow cytometry and left ventricular function by 2-D Echo were measured on admission , at discharge and at 4 months follow up . RESULTS We found that EPC count was similar in the two groups of patients both on admission and at discharge . At follow up , however , EPC count was higher in patients r and omized to IT compared to patients r and omized to ST ( 7.59+/-7.30 vs 3.04+/-3.93 , p=0.04 ) . However , LV volumes , ejection fraction and wall motion score index were similar in both groups . CONCLUSIONS An intensive statin treatment after primary or rescue PCI is associated with a higher EPC count at follow up as compared to st and ard treatment . This beneficial effect did not translate in an improvement of LV function CONTEXT Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions . OBJECTIVE To explore whether the association between funding and conclusions in r and omized drug trials reflects treatment effects or adverse events . DESIGN Observational study of 370 r and omized drug trials included in meta-analyses from Cochrane review s selected from the Cochrane Library , May 2001 . From a r and om sample of 167 Cochrane review s , 25 contained eligible meta-analyses ( assessed a binary outcome ; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment ) . The primary binary outcome from each meta- analysis was considered the primary outcome for all trials included in each meta- analysis . The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect , adverse events , and additional confounding factors ( method ological quality , control intervention , sample size , publication year , and place of publication ) . MAIN OUTCOME MEASURE Conclusions in trials , classified into whether the experimental drug was recommended as the treatment of choice or not . RESULTS The experimental drug was recommended as treatment of choice in 16 % of trials funded by nonprofit organizations , 30 % of trials not reporting funding , 35 % of trials funded by both nonprofit and for-profit organizations , and 51 % of trials funded by for-profit organizations ( P<.001 ; chi2 test ) . Logistic regression analyses indicated that funding , treatment effect , and double blinding were the only significant predictors of conclusions . Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice ( odds ratio , 5.3 ; 95 % confidence interval , 2.0 - 14.4 ) compared with trials funded by nonprofit organizations . This association did not appear to reflect treatment effect or adverse events . CONCLUSIONS Conclusions in trials funded by for-profit organizations may be more positive due to biased interpretation of trial results . Readers should carefully evaluate whether conclusions in r and omized trials are supported by data CONTEXT Percutaneous coronary intervention ( PCI ) is associated with excellent short-term improvements in ischemic symptoms , yet only three fifths of PCI patients at 5 years and one third of patients at 10 years remain free of major adverse cardiac events ( MACE ) . OBJECTIVE To determine whether treatment with fluvastatin reduces MACE in patients who have undergone PCI . DESIGN AND SETTING R and omized , double-blind , placebo-controlled trial conducted at 77 referral centers in Europe , Canada , and Brazil . PATIENTS A total of 1677 patients ( aged 18 - 80 years ) recruited between April 1996 and October 1998 with stable or unstable angina or silent ischemia following successful completion of their first PCI who had baseline total cholesterol levels between 135 and 270 mg/dL ( 3.5 - 7.0 mmol/L ) , with fasting triglyceride levels of less than 400 mg/dL ( 4.5 mmol/L ) . INTERVENTIONS Patients were r and omly assigned to receive treatment with fluvastatin , 80 mg/d ( n = 844 ) , or matching placebo ( n = 833 ) at hospital discharge for 3 to 4 years . MAIN OUTCOME MEASURE Survival time free of MACE , defined as cardiac death , nonfatal myocardial infa rct ion , or reintervention procedure , compared between the treatment and placebo groups . RESULTS Median time between PCI and first dose of study medication was 2.0 days , and median follow-up was 3.9 years . MACE-free survival time was significantly longer in the fluvastatin group ( P = .01 ) . One hundred eighty-one ( 21.4 % ) of 844 patients in the fluvastatin group and 222 ( 26.7 % ) of 833 patients in the placebo group had at least 1 MACE ( relative risk [ RR ] , 0.78 ; 95 % confidence interval [ CI ] , 0.64 - 0.95 ; P = .01 ) . This result was independent of baseline total cholesterol levels ( above [ RR , 0.76 ; 95 % CI , 0.56 - 1.04 ] vs below [ RR , 0.77 ; 95 % CI , 0.57 - 1.02 ] the median ) . In subgroup analysis , the risk of MACE was reduced in patients with diabetes ( n = 202 ; RR , 0.53 ; 95 % CI , 0.29 - 0.97 ; P = .04 ) and in those with multivessel disease ( n = 614 ; RR , 0.66 ; 95 % CI , 0.48 - 0.91 ; P = .01 ) who received fluvastatin compared with those who received placebo . There were no instances of creatine phosphokinase elevations 10 or more times the upper limit of normal or rhabdomyolysis in the fluvastatin group . CONCLUSION Fluvastatin treatment in patients with average cholesterol levels undergoing their first successful PCI significantly reduces the risk of major adverse cardiac events Background —Recent clinical trials have demonstrated that aggressive lipid lowering by statins could prevent recurrent events after acute coronary syndrome ( ACS ) . We hypothesized that this efficacy was caused by a significant reduction in plaque volume by aggressive LDL cholesterol ( LCL-C ) lowering . The present study investigated the effect of early statin treatment on plaque volume of a nonculprit lesion by serial volumetric intravascular ultrasound in patients with ACS . Methods and Results —Seventy patients with ACS were enrolled . All patients underwent emergency coronary angiography and percutaneous coronary intervention ( PCI ) .  They were r and omized to intensive lipid-lowering therapy ( n=35 ; atorvastatin 20 mg/d ) or control ( n=35 ) groups after PCI . Volumetric intravascular ultrasound analyses were performed at baseline and 6-month follow-up for a non-PCI site in 48 patients ( atorvastatin , n=24 ; control , n=24 ) . LDL-C level was significantly decreased by 41.7 % in the atorvastatin group compared with the control group , in which LDL-C was increased by 0.7 % ( P<0.0001 ) . Plaque volume was significantly reduced in the atorvastatin group ( 13.1±12.8 % decrease ) compared with the control group ( 8.7±14.9 % increase ; P<0.0001 ) . Percent change in plaque volume showed a significant positive correlation with follow-up LDL-C level ( R=0.456 , P=0.0011 ) and percent LDL-C reduction ( R=0.612 , P<0.0001 ) , even in patients with baseline LDL-C < 125 mg/dL. Conclusions —Early aggressive lipid-lowering therapy by atorvastatin for 6 months significantly reduced the plaque volume in patients with ACS . Percent change in plaque volume showed a significant positive correlation with percent LDL-C reduction , even in patients with low baseline Composite outcomes , in which multiple end points are combined , are frequently used as primary outcome measures in r and omized trials and are often associated with increased statistical efficiency . However , such measures may prove challenging for the interpretation of results . In this article , we examine the use of composite outcomes in major clinical trials , assess the arguments for and against them , and provide guidance on their application and reporting . To assess incidence and quality of reporting , we systematic ally review ed the use of composite end points in clinical trials in Annals of Internal Medicine , BMJ , Circulation , Clinical Infectious Diseases , Journal of the American College of Cardiology , JAMA , Lancet , New Engl and Journal of Medicine , and Stroke from 1997 through 2001 using a sensitive search strategy . We selected for review 167 original reports of r and omized trials ( with a total of 300 276 patients ) that included a composite primary outcome that incorporated all-cause mortality .  Sixty-three trials ( 38 % ) were neutral both for the primary end point and the mortality component . Sixty trials ( 36 % ) reported significant results for the primary outcome measure but not for the mortality component . Only 6 trials ( 4 % ) were significant for the mortality component but not for the primary composite outcome , whereas 19 trials ( 11 % ) were significant for both . Twenty-two trials ( 13 % ) were inadequately reported . Our review suggests that reporting of composite outcomes is generally inadequate , implying that the results apply to the individual components of the composite outcome rather than only to the overall composite . Current guidelines for the undertaking and reporting of clinical trials could be revised to reflect the common use of composite outcomes in clinical trials Effects of atorvastatin on  early recurrent ischemic events in acute coronary syndromes . The MIRACL study : A r and omized controlled trial OBJECTIVES The objective of this study was to evaluate whether the regressive effects of aggressive lipid-lowering therapy with atorvastatin on coronary plaque volume ( PV ) in patients with acute coronary syndrome ( ACS ) are generalized for other statins in multicenter setting . BACKGROUND A previous single-center study reported beneficial regressive effects of atorvastatin in patients with ACS on PV of the nonculprit site by intravascular ultrasound ( IVUS ) evaluation . The effect of statins other than atorvastatin on PV has not been evaluated in the setting of ACS . METHODS The JAPAN-ACS ( Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome ) study was a prospect i ve , r and omized , open-label , parallel group study with blind end point evaluation conducted at 33 centers in Japan . A total of 307 patients with ACS undergoing IVUS-guided percutaneous coronary intervention were r and omized , and 252 patients had evaluable IVUS examinations at baseline and 8 to 12 months ' follow-up . Patients were r and omly assigned to receive either 4 mg/day of pitavastatin or 20 mg/day of atorvastatin . The primary end point was the percentage change in nonculprit coronary PV . RESULTS The mean percentage change in PV was -16.9 + /- 13.9 % and -18.1 + /- 14.2 % ( p = 0.5 ) in the pitavastatin and atorvastatin groups , respectively , which was associated with negative vessel remodeling . The upper limit of 95 % confidence interval of the mean difference in percentage change in PV between the 2 groups ( 1.11 % , 95 % confidence interval : -2.27 to 4.48 ) did not exceed the pre-defined noninferiority margin of 5 % . CONCLUSIONS The administration of pitavastatin or atorvastatin in patients with ACS equivalently result ed in significant regression of coronary PV ( Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome ; NCT00242944 ) The aim of our study was to evaluate whether a single dose of cerivastatin at the time of admission of patients with unstable angina pectoris ( UAP ) or non-Q-wave myocardial infa rct ion ( NQMI ) can influence the serum level of C-reactive protein ( CRP ) , interleukin-6 ( IL-6 ) and interleukin-8 ( IL-8 ) 24 h later . Forty-four patients with rest chest pain and subendocardial ischemia on ECG were r and omized to receive cerivastatin 0.3 mg at the time of admission ( group C+ ) to st and ard therapy or to remain just on st and ard therapy ( group C− ) . Blood sample s for determination of troponin I ( TI ) , CRP , IL-6 and IL-8 were collected at admission ( entry level ) and 24 h later ( final level ) . Patients with non-physiological baseline levels of TI  , as well as patients with progression to Q wave MI were excluded . All baseline , clinical and demographic data and final values of TI were comparable in the two groups . In patients treated with cerivastatin ( group C+ , n = 13 ) we observed decrease in the CRP level ( −6.73 ± 3.93 mg/L ) ; on the other h and , in group C− ( n = 17 ) the CRP level increased ( + 7.92 ± 2.77 mg/L , p = 0.004 ) . Similar differences were observed also in IL-6 : in group C+ the level was significantly reduced as compared with the increase in group C− ( −0.76 ± 0.52 vs. 4.58 ± 1.49 ng/L , p = 0.005 ) . The level of IL-8 was not affected . Our results suggest that early treatment with cerivastatin can decrease the serum level of CRP and IL-6 in patients with UAP/NQMI ; this might positively influence their prognosis . Nevertheless , further studies are needed to support this hypothesis BACKGROUND It is unclear whether early initiation of low-dose pravastatin therapy can reduce the occurrence of major adverse cardiac events after acute myocardial infa rct ion ( AMI ) . METHODS AND RESULTS The study group comprised 353 patients with AMI who had plasma total cholesterol levels of 200 - 250 mg/dl and triglyceride levels < 300 mg/dl . The patients were r and omly assigned to either receive pravastatin ( 10 mg/daily , n=176 ) or not ( n=177 ) . The primary endpoint was a composite of death , nonfatal myocardial infa rct ion ( MI ) , unstable angina ( UA ) , stroke , revascularization , and rehospitalization because of other cardiovascular disease . The follow-up period was 9 months . The primary endpoint occurred in 31 patients ( 17.9 % ) in the pravastatin group and 55 patients ( 31.4 % ) in the non-pravastatin group ( relative risk , 0.56 ; 95 % confidence interval , 0.36 - 0.87 ) . There were no significant differences in the risk of death , nonfatal MI , UA , and stroke between the 2 groups , although the pravastatin group had a lower risk of need for revascularization . CONCLUSION For patients with AMI , early and low-dose pravastatin therapy ( 10 mg/daily ) reduces recurrent major adverse cardiac events , mostly the requirement for revascularization BACKGROUND Lipid-lowering agents are known to reduce long-term mortality in patients with stable coronary disease or significant risk factors . However , the effect of lipid-lowering therapy on short-term mortality immediately after an acute coronary syndrome has not been determined . We did an observational study using data from two r and omised trials to investigate this issue . METHODS We used data from the GUSTO IIb and PURSUIT trials to compare all-cause mortality among patients with acute coronary syndromes who were discharged on lipid-lowering agents ( n=3653 ) with those who were not ( n=17,156 ) . A propensity analysis was done to adjust for presumed selection biases in the prescription of lipid-lowering agents . FINDINGS Lipid-lowering therapy was associated with a smaller proportion of deaths at 30 days ( 17 [ 0.5 % ] vs 179 [ 1.0 % ] , hazard ratio 0.44 [ 95 % CI 0.27 - 0.73 ] , p=0.001 ) and at 6 months ( 63 [ 1.7 % ] vs 605 [ 3.5 % ] , 0.48 [ 0.37 - 0.63 ] , p<0.0001 ) . After adjustment for the propensity to be prescribed lipid-lowering agents and other potential confounders , prescription of a lipid-lowering agent at discharge remained associated with a reduced risk of death at 6 months ( 0.67 [ 0.48 - 0.95 ] , p=0.023 ) . INTERPRETATION Prescription of a lipid-lowering drug at hospital discharge was independently associated with reduced short-term mortality among patients after an acute coronary syndrome This clinical investigation was design ed and undertaken to test the hypothesis that the addition of high-dose atorvastatin ( 80 mg/day ) to conventional medical treatment early after either unstable angina pectoris ( UAP ) or non – Q-wave acute myocardial infa rct ion ( AMI ) could reduce ischemic recurrences .  All patients consecutively admitted to our institution between January 1999 and July 2001 for UAP or non – Q-wave AMI were prospect ively screened for inclusion in the study . In all cases the diagnosis of UAP or non – Q-wave AMI was made in accordance with previously reported criteria . 1 To be enrolled in the trial , patients were required to meet the following criteria : ( 1 ) angiographic evidence of severe and diffuse coronary artery disease , that was not amenable to direct revascularization by coronary artery bypass grafting or percutaneous transluminal coronary angioplasty  , as determined by a cardiac surgeon and an interventional cardiologist during the index admission ; ( 2 ) objective evidence of symptomatic reversible myocardial ischemia ( 0.1 mV ST-segment depression on the electrocardiogram ) at a low exercise workload ( 4 METs ) while receiving medical treatment ( 2 antianginal medications at maximal tolerated doses ) , as assessed by treadmill ergometry ( Bruce ’s protocol ) before discharge ; and ( 3 ) left ventricular ejection fraction 35 % . Exclusion criteria were the presence of congestive heart failure , the need for continuous use of intravenous antianginal medications , and the presence of any major concurrent illness . The study was planned as an open-label , prospect i ve , r and omized , controlled trial with parallel groups . Before enrollment , all patients were receiving maximal conventional combination therapy ( nitrates , calcium antagonists , and blockers ) , including 2 medications at maximal tolerated doses in all cases . All patients provided informed consent to take part in the investigation . At discharge from the hospital , included AIMS Controversy exists with regard to the influence of APOE polymorphisms on coronary heart disease development and on the efficacy of statin treatment . we investigated the relationship between apoe , mortality and the response to treatment in Mediterranean myocardial infa rct ion ( mi ) survivors . METHODS AND RESULTS We analysed 3304 Italian patients with MI r and omized to pravastatin or no treatment in the GISSI-Prevenzione study , with a mean follow-up time of 23.0 + /- 6.7 months ( median 24.3 months ) .  Mortality curves were calculated using Kaplan-Meier method , and differences in survival were tested using the log-rank test . There were 109 deaths during follow-up . Patients treated with pravastatin showed a significant decrease in mortality compared with non-treated patients ( HR 0.67 , 95 % confidence interval 0.45 - 0.97 , P = 0.038 ) . Among the 3304 patients , 554 ( 16.8 % ) were epsilon4 carriers and 2750 ( 83.2 % ) were non-epsilon4 carriers . No significant difference in terms of mortality was observed between the epsilon4 and the non-epsilon4 carriers ( 3.61 % vs. 3.24 % , P = 0.67 ) . However , although in non-epsilon4 carriers no significant difference in mortality was observed between patients treated with pravastatin and non-treated ( 2.81 % vs. 3.67 % , P = 0.21 ) , among the epsilon4 carriers a significant reduction in mortality was observed in patients treated compared with non-treated ( 1.85 % vs. 5.28 % , P = 0.023 ) . CONCLUSION We found that epsilon4 allele is a determinant of pravastatin response in terms of survival . Though in the entire population investigated , we found a beneficial effect of pravastatin in terms of survival , only the epsilon4 carriers seemed to have gained a significant benefit from this treatment . We suggest that the effect of statins is of particular interest in this fraction of the population . Genetic markers can help in identifying patients that benefit more from statin treatment BACKGROUND Cholesterol lowering reduces coronary events . One mechanism could be improvement of endothelial function . In line with this hypothesis , this study investigates whether cholesterol reduction can result in rapid improvement of endothelial function  after acute coronary syndromes . METHODS AND RESULTS Patients with acute myocardial infa rct ion or unstable angina and total cholesterol levels at admission > /=5.2 mmol/L or LDL > /=3.4 mmol/L were r and omized to placebo ( n=30 ) or pravastatin 40 mg daily ( n=30 ) for 6 weeks . Brachial ultrasound was used to measure endothelium-dependent flow-mediated dilatation ( FMD ) and response to endothelium-independent nitroglycerin . Changes in the levels of markers of platelet activation , coagulation factors , and plasma endothelin levels were also assessed . Total and LDL cholesterol levels were similar at admission and before r and omization in both groups . With pravastatin , but not with placebo , they decreased by 23 % ( P<0.05 ) and 33 % ( P<0.01 ) , respectively . FMD was unchanged with placebo , 5.43+/-0.74 % ( mean+/-SEM ) to 5.84+/-0.81 % , but increased with pravastatin , 4.93+/-0.81 % to 7.0+/-0.79 % ( P=0.02 ) , representing a 42 % relative increase . Responses to nitroglycerin were similar during the time course of the study in the 2 groups . Markers of platelet activity , coagulation factors , and endothelin levels were not affected by pravastatin . CONCLUSIONS Cholesterol reduction with pravastatin initiated early after acute coronary syndromes rapidly improves endothelial function after 6 weeks of therapy 1 Previous studies have demonstrated that early statin therapy after acute coronary syndrome decreases inflammation and mortality rates . The dose – response relationship for atorvastatin in elderly patients with unstable angina ( UA ) during early hospitalization in terms of lowering inflammatory factors , improving vascular endothelium function and safety is unclear . 2 In the present study , 166 consecutive patients with UA who were ≥ 60 years of age were r and omly assigned , in a double‐blind manner , to receive 80 or 20 mg/day atorvastatin . High‐sensitivity C‐reactive protein , interleukin‐6 , tumour necrosis factor‐α , fibrinogen and lipid levels were measured at admission and 1 , 2 and 8 weeks later . Vascular endothelial function was measured and the safety of the drug was monitored . 3 Levels of inflammatory factors were significantly lower in patients on 80 mg atorvastatin than in those on 20 mg atorvastatin at 2 and 8 weeks . Atorvastatin 80 mg not only result ed in a significant improvement in vascular endothelial function during early hospitalization for UA over that seen in patients on 20 mg atorvastatin , but also reduced lipid levels to a greater extent . At 8 weeks , almost all patients showed good tolerance of 80 mg/day atorvastatin . 4 The results of the present study indicate that intensive statin therapy with high‐dose ( 80 mg/day ) atorvastatin is more efficacious than and as safe as 20 mg/day atorvastatin when administered to elderly patients during early hospitalization for UA AIM To determine whether statin therapy initiated early in acute myocardial infa rct ion together with thrombolytic therapy in patients with acute myocardial infa rct ion results in clinical benefit through early plaque stabilization . METHODS AND RESULTS The study population consisted of 77 patients who underwent coronary balloon angioplasty of the infa rct -related artery during the first month of acute myocardial infa rct ion . These patients belonged to the cohort of the Pravastatin Turkish Trial ( PTT ) . Forty of them were assigned r and omly to have immediate pravastatin ( 40 mg/day ) therapy adjunctive to thrombolytic therapy regardless of serum lipid levels and received statin treatment throughout the study . Lipid levels were determined immediately after admission and before angioplasty and at the end of 6 months . Patients were re-evaluated clinical ly and angiographically for cardiovascular adverse events and restenosis after a 6-month follow-up period . The baseline angiographic and clinical characteristics of the two groups were similar . The incidence of angina was significantly lower in the pravastatin group ( 30.0 % , 12 patients ) compared to the control group ( 59.5 % , 22 patients ) ( p = 0.018 ) . The cumulative major adverse cardiac events in the pravastatin group were significantly lower when compared to the control group ( 32.5 % vs. 75.6 % , p = 0.0001 ) . CONCLUSIONS Early initiation of pravastatin therapy immediately after an acute myocardial infa rct ion significantly decreased the frequency of major cardiac adverse events . Such early potential clinical benefits further strengthen the rationale for starting statin treatment as soon as possible after acute coronary events particularly in patients in whom invasive intervention is planned Background : Myocardial necrosis is related to higher incidence of cardiovascular events and higher mortality rates during follow‐up . Statins have been demonstrated to lower the risk of periprocedural myocardial infa rct ion . The aim of this study is to evaluate the safety and efficacy of intensive statin therapy and the long‐term outcome of patients in the Asian population . Study design : Approximately 1,100 patients with stable angina or non‐ST elevation acute coronary syndrome undergoing selective percutaneous coronary intervention ( PCI ) are enrolled in this study . Patients are r and omized either to the experimental group ( 80 mg atorvastatin 80 mg/day × 2 days before and 40 mg/day × 30 days after PCI ) or to the control group ( usual care ) . Creatine kinase‐MB ( CK‐MB ) , troponin I ( cTnI ) , and serum creatine are measured at 24 hours after the procedure . The total follow‐up period is 6 months . The primary objective is to evaluate the efficacy  of intensive atorvastatin treatment compared with usual care in reducing 30‐day primary cardiovascular endpoints in patients undergoing selective PCI . Secondary endpoints are changes in myocardial biomarkers ( cTnI , CK‐MB ) and hs‐CRP , CIN morbidity , 6‐month clinical outcomes , and safety . Conclusion : The result of the ISCAP study will provide important evidence on the efficacy and safety of periprocedural serial intensive statin treatment in Asian patients with coronary artery disease undergoing selective PCI . © 2011 Wiley Periodicals , Secondary prevention of coronary heart disease by antilipidemic therapy beginning at > or =3 months after an acute coronary syndrome is well documented . The impact , however , of immediate initiation of antilipidemic therapy on coronary stenoses and clinical outcome in patients with acute coronary syndrome is unknown . In our study , patients were r and omized , on average , 6 days after an acute myocardial infa rct ion and /or percutaneous transluminal coronary angioplasty secondary to unstable angina , to pravastatin ( combined , when necessary , with cholestyramine and /or nicotinic acid )  to achieve low-density lipoprotein cholesterol levels of < or = 130 mg/dl ( group A , n = 70 ) . In controls ( group B , n = 56 ) , antilipidemic therapy was determined by family physicians  . Quantitative coronary angiography was performed at inclusion , and at 6- and 24-month follow-up . The combined clinical end points were total mortality , cardiovascular death , nonfatal myocardial infa rct ion , need for coronary intervention , stroke , and new onset of peripheral vascular disease . Minimal lumen diameter in group A increased by 0.05 + /- 0.20 mm after 6 months and 0.13 + /- 0.29 mm after 24 months , whereas it decreased by 0.08 + /- 0.20 mm and 0.18 + /- 0.27 mm , respectively , in group B ( p = 0.004 at 6 months and p < 0.001 at 24 months ) . After 2 years , 29 patients of 56 patients in group B , but only 16 of 70 patients in group A , experienced a clinical end point ( p = 0.005 ; odds ratio 0.28 , confidence intervals 0.13 to 0.6 ) . We conclude that pravastatin-based therapy initiated immediately after an acute coronary syndrome is well tolerated and safe , lessens coronary atherosclerosis , and has a pronounced clinical benefit BACKGROUND Lipid-lowering agents are known to reduce long-term mortality in patients with stable angina or multiple risk factors . However , the effects of lipid-lowering treatment on inflammatory process during and immediately after the acute phase of unstable angina remain unclear . In this study we assessed the effects of low-dose atorvastatin treatment , on inflammatory process in patients admitted for unstable angina with low cholesterol level . METHODS Forty-seven normocholesterolemic patients with unstable angina were r and omized into two groups , and received atorvastatin 10 mg/day ( n = 24 ) or no statin ( n = 23 ) for 6 weeks . Circulating levels of inteleukin 6 ( IL-6 ) , monocyte chemoattractant protein-1 ( MCP-1 ) , tumor necrosis factor alpha ( TNF-alpha ) and soluble vascular cell adhesion molecule ( sVCAM-1 ) were measured by their admission , and at the 1st and 6th week of the study . RESULTS Serum levels of MCP-1 and sVCAM-1 were significantly increased in the control group ( p < 0.05 ) while remained unaffected in the atorvastatin-treated group six weeks after admission . However , IL-6 and TNF-alpha levels were similarly decreased in both atorvastatin-treated and control groups . CONCLUSION Low-dose atorvastatin treatment modifies inflammatory process in patients with unstable angina and low cholesterol level , an effect seen at 6 weeks but not 1 week after admission Background Statins have been proved to be effective in reduction of mortality and morbidity when started in the early secondary prevention in stabilized patients after acute coronary syndrome ( ACS ) . The safety and efficacy of statin administration directly in the first-line therapy in unstable ACS patients is not clear . The aim of our study was , therefore , to assess the effect of statin treatment initiated immediately at hospital admission of patients with ACS . Methods The trial was stopped prematurely after enrollment of one hundred and fifty-six patients with ACS that were r and omized at admission to fluvastatin 80 mg ( N = 78 ) or placebo ( N = 78 ) . Study medication was administered immediately after r and omization and then once daily for 30 days ; all patients were then encouraged to continue in open-label statin therapy and at the end of one-year follow-up 75 % in the fluvastatin group and 78 % in the placebo group were on statin therapy . Results We did not demonstrate any difference between groups in the level of C-reactive protein , interleukin 6 , and pregnancy-associated plasma protein A on Day 2 and Day 30 ( primary endpoint ) . Fluvastatin-therapy , however , significantly reduced one-year occurrence of major adverse cardiovascular events ( 11.5 % vs. 24.4 % , odds ratio ( OR ) 0.40 , 95 % CI 0.17 - 0.95 , P = 0.038 ) . This difference was caused mainly by reduction of recurrent symptomatic ischemia ( 7.7 % vs. 20.5 % , OR 0.32 , 95 % CI 0.12 - 0.88 , P = 0.037 ) . Conclusions This study failed to prove the effect of fluvastatin given as first-line therapy of ACS on serum markers of inflammation and plaque instability . Fluvastatin therapy was , however , safe and it may reduce cardiovascular event rate that supports immediate use of a statin in patients admitted for ACS.Trial registration BACKGROUND Statin therapy prior to percutaneous coronary intervention ( PCI ) is associated with reduced mortality and periprocedural myocardial injury after PCI . We studied whether single high dose statin loading is beneficial on the outcome of patients with acute coronary syndrome ( ACS ) underwent PCI . METHODS Consecutive 445 patients with ACS who underwent PCI were r and omly assigned to either the group of no statin treatment before PCI ( Control group : n=220 , 63+/-11 years , male 62 % ) or the group of 40 mg rosuvastatin loading before PCI ( Rosuvastatin group : n=225 , 64+/-10 years , male 60 % ) . Incidence of periprocedural myocardial injury was assessed by analysis of creatinine kinase-MB ( CK-MB ) and cardiac troponin T before PCI , at 6 h and the next morning after PCI . RESULT There were no significant differences in clinical characteristics between the two groups . After PCI , incidence of periprocedural myocardial injury was higher in control than in rosuvastatin group ( 11.4 % versus 5.8 % , p=0.035 ) . Mean preprocedural CK-MB and high sensitivity C-reactive protein were similar between the two groups , whereas after PCI , peak values of both markers were elevated significantly higher in control than in rosuvastatin group . Multivariate analysis revealed that no prior use of statin ( OR=2.2 ; 95 % CI=1.1 - 4.6 ; p=0.029 ) , procedural complication ( OR=3.1 ; 95 % CI=1.4 - 6.9 ; p=0.007 ) and multi-vessel disease ( OR=2.6 ; 95 % CI=1.0 - 6.6 ; p=0.039 ) were the independent predictors for periprocedural myocardial infa rct ion . CONCLUSION Single high dose of rosuvastatin prior to PCI reduces periprocedural myocardial injury in patients with ACS Background Activation of inflammatory pathways plays an important contributory role in coronary plaque instability and subsequent rupture , which can lead to the development of acute coronary syndrome ( ACS ) . Elevated levels of serum inflammatory markers such as C-reactive protein ( CRP ) represent independent risk factors for further cardiovascular events . Recent evidence indicates that in addition to lowering cholesterol levels , statins also decrease levels of inflammatory markers . Previous controlled clinical trials reporting the positive effects of statins in participants with ACS were design ed for very early secondary prevention . To our knowledge , no controlled trials have evaluated the potential benefits of statin therapy , beginning immediately at the time of hospital admission . A previous pilot study performed by our group focused on early initiation of cerivastatin therapy . We demonstrated a highly significant reduction in levels of inflammatory markers ( CRP and interleukin-6 ) . Based on these preliminary findings , we are conducting a clinical trial to evaluate the efficacy of another statin , fluvastatin , as an early intervention in patients with ACS . Methods The FACS-trial ( Fluvastatin in the therapy of Acute Coronary Syndrome ) is a multicenter , r and omized , double-blind , placebo-controlled study evaluating the effects of fluvastatin therapy initiated at the time of hospital admission . The study will enroll 1,000 participants admitted to hospital for ACS ( both with and without ST elevation ) . The primary endpoint for the study is the influence of fluvastatin therapy on levels of inflammatory markers ( CRP and interleukin-6 ) and on pregnancy associated plasma protein A ( PAPP-A ) . A combined secondary endpoint is 30-day and one-year occurrence of death , nonfatal myocardial infa rct ion , recurrent symptomatic ischemia , urgent revascularization , and cardiac arrest . Conclusion The primary objective of the FACS trial is to demonstrate that statin therapy , when started immediately after hospital admission for ACS , results in reduction of inflammation and improvement of prognosis . This study may contribute to new knowledge regarding therapeutic strategies for patients suffering from ACS and may offer additional clinical indications for the use of statins AIMS Residual ischaemia following acute myocardial infa rct ion ( AMI ) is related to an adverse outcome , although the effect of early initiation of statin therapy is unknown . METHODS A r and omized , placebo-controlled , double-blind , parallel study was performed , which compared fluvastatin 80 mg daily with placebo in patients with an AMI and total cholesterol of < 6.5 mmol.l(-1 ) . Ischaemia was measured by ambulatory electrocardiographic ( AECG ) monitoring over 48-h at baseline , after 6 weeks and at 12 months . RESULTS Five hundred and forty patients were included ( 83 % male , age 61+/-11 years ) ; 43 % had an anterior AMI and 50 % were treated with fibrinolytics in the acute phase . After 12 months , the total cholesterol ( TC ) level was reduced by 13 % and LDL-C ( low-density-lipoprotein cholesterol ) by 21 % ( from 3.5 mmol.l(-1 ) to 2.7 mmol.l(-1 ) ) in the fluvastatin treatment group . Both TC and LDL increased by 9 % in the placebo group ( P<0.001 between groups ) . At baseline , ischaemia on AECG was present in only 11 % of patients , and absent in 77 % ; in the remaining 11 % , recordings were technically inadequate . After 6 weeks , 32/48 ( 67 % ) , and 12 months 35/46 ( 76 % ) of the patients with ischaemia on the baseline AECG , no longer showed signs of ischaemia . Nevertheless , ischaemia at baseline was predictive for the occurrence of any major clinical event ( RR=2.35 ; 95 % CI 1.39 - 3.2;P < 0.001 ) . Fluvastatin treatment did not affect ischaemia on AECG , nor the occurrence of any major clinical events as compared to placebo . Post-hoc analysis in patients with the most pronounced ischaemia at baseline showed a trend for a beneficial effect of fluvastatin on major clinical events ( P=0.084 ) . CONCLUSION Residual ischaemia after AMI is observed less frequently in the present study , than in earlier studies , although it is predictive for future cardiovascular events . As a result , the present study was underpowered , and no effect of fluvastatin on AECG ischaemia , or major clinical events in the first year after AMI , could be detected . The present data do not confirm other reports which support widespread use of statin treatment early after AMI AIMS HMG-CoA reductase inhibitors ( statins ) reduce cardiovascular mortality and morbidity in patients with stable coronary artery disease as well as acute coronary syndrome ( ACS ) . It is unclear how rapidly the beneficial effects of statins occur in patients with ACS and whether these drug properties are related to lipid lowering . METHODS AND RESULTS Patients with troponin-positive ACS ( n=35 ) were r and omized to 20 mg/day rosuvastatin therapy or to placebo treatment . Anti-inflammatory effects of rosuvastatin measured by lymphocyte intracellular cytokine production were taken before initiation of treatment and on days 1 , 3 , and 42 . Compared with placebo , rosuvastatin treatment significantly reduced plasma concentrations of pro-inflammatory cytokines TNF-alpha and IFN-gamma at 72 h. Rosuvastatin also induced a rapid and significant reduction of TNF-alpha and IFN-gamma production in stimulated T-lymphocytes at 72 h. When compared with placebo , rosuvastatin inhibited the Th-1-immune response measured at 72 h. CONCLUSION Rosuvastatin exerts rapid immunomodulatory effects on the level of T-cell activation in patients with ACS BACKGROUND Studies in Western population s have shown the benefits of pretreatment with atorvastatin in preventing cardiovascular events in patients , including those with acute coronary syndromes ( ACS ) , undergoing percutaneous coronary intervention ( PCI ) . However , data concerning the value of such therapy in Asian patients are limited . The primary objective of the present study is to evaluate the efficacy of atorvastatin in reducing cardiovascular outcomes in Asian patients with non-ST-segment elevation (NSTE)-ACS following hospital admission for early PCI ( within 72 h of the onset of symptoms ) . Secondary objectives are to assess the effects of atorvastatin on cardiac biomarker levels , and the safety and tolerability profile of atorvastatin . METHODS This study is a prospect i ve , multicenter , open-label trial design ed to enroll 350 statin-naïve patients with NSTE-ACS scheduled for PCI in China and the Republic of Korea . Patients are r and omized to either usual care or atorvastatin treatment groups , with patients in both treatment groups receiving usual care including atorvastatin 40 mg/day for 30 days post-PCI . Patients in the atorvastatin group receive additional doses of atorvastatin 80 mg at 12 h pre-PCI and 40 mg at 2 h pre-PCI . The primary end point is the incidence of major adverse cardiac events ( death , myocardial infa rct ion , and target vessel revascularization ) at 30 days post-PCI . CONCLUSIONS The present study will provide valuable insights into whether the benefits of atorvastatin pretreatment extend to Asian patients with ACS undergoing interventions . Enhanced treatment of these patients will be an important contribution towards alleviating the increasing burden of cardiovascular disease in Asian countries CONTEXT Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol ( LDL-C ) than is commonly applied clinical ly will provide further benefit in stable coronary artery disease . OBJECTIVE To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infa rct ion ( MI ) . DESIGN , SETTING , AND PARTICIPANTS The IDEAL study , a prospect i ve , r and omized , open-label , blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practice s in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years , which enrolled 8888 patients aged 80 years or younger with a history of acute MI . INTERVENTIONS Patients were r and omly assigned to receive a high dose of atorvastatin ( 80 mg/d ; n = 4439 ) , or usual-dose simvastatin ( 20 mg/d ; n = 4449 ) . MAIN OUTCOME MEASURE Occurrence of a major coronary event , defined as coronary death , confirmed nonfatal acute MI , or cardiac arrest with resuscitation . RESULTS During treatment , mean LDL-C levels were 104 ( SE , 0.3 ) mg/dL in the simvastatin group and 81 ( SE , 0.3 ) mg/dL in the atorvastatin group . A major coronary event occurred in 463 simvastatin patients ( 10.4 % ) and in 411 atorvastatin patients ( 9.3 % ) ( hazard ratio [ HR ] , 0.89 ; 95 % CI , 0.78 - 1.01 ; P = .07 ) . Nonfatal acute MI occurred in 321 ( 7.2 % ) and 267 ( 6.0 % ) in the 2 groups ( HR , 0.83 ; 95 % CI , 0.71 - 0.98 ; P = .02 ) , but no differences were seen in the 2 other components of the primary end point . Major cardiovascular events occurred in 608 and 533 in the 2 groups , respectively ( HR , 0.87 ; 95 % CI , 0.77 - 0.98 ; P = .02 ) . Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients ( HR , 0.84 ; 95 % CI , 0.76 - 0.91 ; P<.001 ) . Noncardiovascular death occurred in 156 ( 3.5 % ) and 143 ( 3.2 % ) in the 2 groups ( HR , 0.92 ; 95 % CI , 0.73 - 1.15 ; P = .47 ) . Death from any cause occurred in 374 ( 8.4 % ) in the simvastatin group and 366 ( 8.2 % ) in the atorvastatin group ( HR , 0.98 ; 95 % CI , 0.85 - 1.13 ; P = .81 ) . Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events ; transaminase elevation result ed in 43 ( 1.0 % ) vs 5 ( 0.1 % ) withdrawals ( P<.001 ) . Serious myopathy and rhabdomyolysis were rare in both groups . CONCLUSIONS In this study of patients with previous MI , intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events , but did reduce the risk of other composite secondary end points and nonfatal acute MI . There were no differences in cardiovascular or all-cause mortality .  Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions . Trial Registration Clinical Trials.gov Identifier : NCT00159835 BACKGROUND There is controversy about whether lipid-lowering pharmacotherapy should be initiated immediately after an acute coronary event or only after diet and lifestyle changes have proved inadequate . OBJECTIVE This study , known as the Lipid Intervention Strategies for Coronary Patients Study , compared the efficacy of immediate versus deferred simvastatin treatment in conjunction with dietary advice about reducing lipid levels in hypercholesterolemic patients with acute coronary syndromes . METHODS This r and omized , open-label , parallel-group study included 151 hypercholesterolemic ( low-density lipoprotein cholesterol [ LDL-C ] > 3.0 mmol/L ) men and women aged 35 to 75 years . Within 4 days of diagnosis of acute myocardial infa rct ion ( MI ) or unstable angina pectoris , all patients received dietary advice from a specially trained nurse . Subsequently , patients were r and omized to 2 treatment groups : 1 group received immediate treatment with simvastatin 40 mg/d ; patients in the other group received simvastatin 40 mg/d after 3 months only if their LDL-C remained > 3.0 mmol/L. RESULTS The immediate-simvastatin group ( n = 73 ) and the deferred-simvastatin group ( n = 78 ) were balanced with respect to baseline characteristics . Of the 151 patients , 25 % were women , 25 % had concomitant hypertension , and 75 % had a diagnosis of MI on enrollment . At 3 months , 90 % of the patients receiving dietary advice plus immediate simvastatin treatment had achieved the recommended European target LDL-C level of < 3.0 mmol/L , compared with 7 % of those treated with diet alone . By 6 months , when 92 % of the study participants were receiving simvastatin 40 mg/d , the proportion of patients achieving target LDL-C levels was 92 % in the group that received immediate simvastatin therapy and 81 % in the group that received deferred simvastatin therapy . The reductions in LDL-C ( 42%-48 % ) were considered to be clinical ly comparable between the 2 groups at 12 months . CONCLUSIONS On the basis of these results , we concluded that few patients with hypercholesterolemia and acute coronary syndromes reach the recommended European target LDL-C level of < 3.0 mmol/L with dietary advice alone . However , early treatment with simvastatin 40 mg/d combined with dietary advice and follow-up at a dedicated outpatient clinic specializing in coronary heart disease result ed in 9 out of 10 patients reaching a recommended target LDL-C level of < 3.0 mmol/L. Initiation of simvastatin therapy while a patient is hospitalized may increase the likelihood of the patient 's lipid levels being managed according to current recommendations after he or she is discharged BACKGROUND Lipid-lowering therapy with statins reduces the risk of cardiovascular events , but the optimal level of low-density lipoprotein ( LDL ) cholesterol is unclear . METHODS We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40  mg of pravastatin daily ( st and ard therapy ) with 80 mg of atorvastatin daily ( intensive therapy ) . The primary end point was a composite of death from any cause , myocardial infa rct ion , documented unstable angina requiring rehospitalization , revascularization ( performed at least 30 days after r and omization ) , and stroke . The study was design ed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event . Follow-up lasted 18 to 36 months ( mean , 24 ) . RESULTS The median LDL cholesterol level achieved during treatment was 95 mg per deciliter ( 2.46 mmol per liter ) in the st and ard-dose pravastatin group and 62 mg per deciliter ( 1.60 mmol per liter ) in the high-dose atorvastatin group ( P<0.001 ) . Kaplan-Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group , reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin ( P=0.005 ; 95 percent confidence interval , 5 to 26 percent ) . The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen . CONCLUSIONS Among patients who have recently had an acute coronary syndrome , an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than does a st and ard regimen . These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels Objective : The aim of this pilot study was to determine whether early atorvastatin treatment will reduce left ventricle ( LV ) remodeling , infa rct size , and improve microvascular perfusion . Background : In animal studies , early statin therapy reduces reperfusion injury after a percutaneous coronary intervention ( PCI ) for acute myocardial infa rct ion ( AMI ) . Methods : Forty‐two consecutive patients ( 82 % male , mean age 61.2 ± 9.8 ) who underwent a primary PCI for a first ST‐elevated AMI were r and omized for pretreatment with atorvastatin 80 mg ( n = 20 ) or placebo ( n = 22 ) and continued with the same dosage daily for 1 week . All patients received atorvastatin 80 mg once daily 7 days after primary PCI . The LV function and infa rct size were measured by magnetic resonance imaging within 1 day , at 1 week , and 3 months follow up . The primary endpoint was the end‐systolic volume index ( ESVI ) at 3 months . Secondary endpoints were global LV function measurements , myocardial infa rct size , biochemical cardiac markers , TIMI flow , and ST‐T elevation resolution . Results : ESVI 3 months after AMI was 25.1 mL/m2 in the atorvastatin arm and 25.0 mL/m2 in the placebo arm ( P = 0.74 ) . The differences in change from baseline to 3 months follow up in global LV function and myocardial infa rct size did not differ between both treatment arms . Furthermore , biochemical markers , TIMI flow , and ST‐T elevation resolution did not differ between atorvastatin and placebo arm . Conclusions : In this pilot study , pretreatment with atorvastatin in an acute myocardial infa rct ion does not result in an improved cardiac function , microvascular perfusion , or decreased myocardial infa rct size . © 2012 Wiley Periodicals BACKGROUND Current guidelines recommend an early invasive strategy for patients who have acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level . However , r and omized trials have not shown an overall reduction in mortality , and the reduction in the rate of myocardial infa rct ion in previous trials has varied depending on the definition of myocardial infa rct ion . METHODS We r and omly assigned 1200 patients with acute coronary syndrome without ST-segment elevation who had chest pain , an elevated cardiac troponin T level ( > or = 0.03 mug per liter ) , and either electrocardiographic evidence of ischemia at admission or a documented history of coronary disease to an early invasive strategy or to a more conservative ( selectively invasive ) strategy . Patients received aspirin daily , enoxaparin for 48 hours , and abciximab at the time of percutaneous coronary intervention . The use of clopidogrel and intensive lipid-lowering therapy was recommended . The primary end point was a composite of death , nonfatal myocardial infa rct ion , or rehospitalization for anginal symptoms within one year after r and omization . RESULTS The estimated cumulative rate of the primary end point was 22.7 percent in the group assigned to early invasive management and 21.2 percent in the group assigned to selectively invasive management ( relative risk , 1.07 ; 95 percent confidence interval , 0.87 to 1.33 ; P=0.33 ) . The mortality rate was the same in the two groups ( 2.5 percent ) . Myocardial infa rct ion was significantly more frequent in the group assigned to early invasive management ( 15.0 percent vs. 10.0 percent , P=0.005 ) , but rehospitalization was less frequent in that group ( 7.4 percent vs. 10.9 percent , P=0.04 ) . CONCLUSIONS We could not demonstrate that , given optimized medical therapy , an early invasive strategy was superior to a selectively invasive strategy in patients with acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level BACKGROUND Statins reduce the incidence of cardiovascular events in patients with acute myocardial infa rct ion ( AMI ) . Although all statins are equally effective in secondary prevention , there might be certain differences in the effects of lipophilic and hydrophilic statins . Therefore , our aim is to compare the effectiveness of lipophilic atorvastatin and hydrophilic pravastatin in secondary prevention after AMI . METHODS AND RESULTS This study is a prospect i ve , r and omized , open-label , multicenter study of 500 patients with AMI . Patients that have undergone successful percutaneous coronary intervention will be r and omly allocated to receive either atorvastatin or pravastatin with the treatment goal of lowering their low-density lipoprotein-cholesterol level below 100 mg/dl for 2 years . The primary endpoint will be death due to any cause , nonfatal MI , nonfatal stroke , unstable angina , or congestive heart failure requiring hospital admission , or any type of coronary revascularization . CONCLUSION This is the first multicenter trial to compare the effects and safety of lipophilic and hydrophilic statin therapy in Japanese patients with AMI . It addresses an important issue and could influence the use of statin treatment in the secondary prevention of coronary artery disease OBJECTIVES This analysis from the LUNAR ( Limiting UNdertreatment of lipids in ACS with Rosuvastatin ) study assessed lipid changes 1 to 4 days after onset of acute coronary syndromes ( ACS ) , before initiation of study treatment . BACKGROUND Early studies indicated that cholesterol levels decrease significantly after ACS . However , most studies were small or did not measure low-density lipoprotein cholesterol ( LDL-C ) directly , and many used nonfasting or retrospective data . More recent studies suggest less pronounced changes in cholesterol levels after ACS . METHODS The LUNAR trial is a prospect i ve , multicenter , r and omized , open-label study in adults hospitalized for acute ST-segment elevation myocardial infa rct ion ( STEMI ) , non-STEMI , or unstable angina ( UA ) . Blood sample s were taken at median times after onset of ACS symptoms of 26 h ( Day 1 , fasting or nonfasting sample ) , 43 h ( Day 2 , fasting sample ) , and 84 h ( Day 4 , fasting sample ) for direct measurement of serum lipid levels before study treatments were started . RESULTS Of 507 patients available for analysis , 212 were admitted for STEMI , 176 for non-STEMI , and 119 for UA . The LDL-C levels decreased in the 24 h after admission ( from 136.2 to 133.5 mg/dl ) , followed by an increase over the subsequent 2 days ( to 141.8 mg/dl ) . These changes did not seem to be clinical ly meaningful . Similar changes were observed for total cholesterol and smaller changes for high-density lipoprotein cholesterol ; fasting triglyceride levels did not change . CONCLUSIONS Mean lipid levels vary relatively little in the 4 days after an ACS and can be used to guide selection of lipid-lowering medication OBJECTIVES This study sought to investigate potential protective effects of atorvastatin in patients with acute coronary syndromes ( ACS ) undergoing percutaneous coronary intervention ( PCI ) . BACKGROUND R and omized studies have shown that pretreatment with atorvastatin may reduce periprocedural myocardial infa rct ion in patients with stable angina during elective PCI ; however , this therapy has not been tested in patients with ACS . METHODS A total of 171 patients with non-ST-segment elevation ACS were r and omized to pretreatment with atorvastatin  ( 80 mg 12 h before PCI , with a further 40-mg preprocedure dose [ n = 86 ] ) or placebo ( n = 85 ) . All patients were given a clopidogrel 600-mg loading dose . All patients received long-term atorvastatin treatment thereafter ( 40 mg/day ) . The main end point of the trial was a 30-day incidence of major adverse cardiac events ( death , myocardial infa rct ion , or unplanned revascularization ) . RESULTS The primary end point occurred in 5 % of patients in the atorvastatin arm and in 17 % of those in the placebo arm ( p = 0.01 ) ; this difference was mostly driven by reduction of myocardial infa rct ion incidence ( 5 % vs. 15 % ; p = 0.04 ) . Postprocedural elevation of creatine kinase-MB and troponin-I was also significantly lower in the atorvastatin group ( 7 % vs. 27 % , p = 0.001 and 41 % vs. 58 % , p = 0.039 , respectively ) . At multivariable analysis , pretreatment with atorvastatin conferred an 88 % risk reduction of 30-day major adverse cardiac events ( odds ratio 0.12 , 95 % confidence interval 0.05 to 0.50 ; p = 0.004 ) . CONCLUSIONS The ARMYDA-ACS trial indicates that even short-term pretreatment with atorvastatin may improve outcomes in patients with ACS undergoing early invasive strategy . These findings may support routine use of high-dose statins before intervention in patients with ACS BACKGROUND To evaluate the impact of the extent of coronary disease ( single- or multivessel ) and of fluvastatin treatment on the incidence of long-term cardiac atherosclerotic complications in the Lescol Intervention Prevention Study ( LIPS ) . METHODS A total of 1063 patients with single-vessel disease and 614 patients with multivessel disease were r and omized to receive fluvastatin ( 40 mg bid ) or placebo for at least 3 years following a first successful percutaneous coronary intervention . The incidence of cardiac atherosclerotic events ( cardiac death , non-fatal myocardial infa rct ion , and coronary re- interventions not related to restenosis ) was evaluated . RESULTS Patients with multivessel disease tended to be older and presented a higher prevalence of associated risk factors and cardiovascular antecedents . The presence of multivessel disease markedly increased the risk of cardiac atherosclerotic events compared with single-vessel disease among patients allocated to placebo ( RR 1.67 [ 95 % CI : 1.24 - 2.25 ] ; p<0.001 ) . In patients treated with fluvastatin , however , no significant differences in long-term outcomes were observed between patients with multivessel disease and patients single-vessel disease ( RR 1.28 [ 95 % CI : 0.90 - 1.81 ] ; p=0.2 ) . CONCLUSIONS Multivessel coronary disease impaired the 4-year outcomes after percutaneous intervention . However , the hazardous effect of multivessel disease was significantly reduced by long-term fluvastatin treatment Context While the benefits of statins in the primary and secondary prevention of coronary artery disease are clear , the value of statin therapy in acute coronary syndromes is uncertain . Contribution Analyzing data from a large , international observational study of acute coronary syndromes , these investigators identified associations between statin use before and during acute coronary events and favorable outcomes . Caution s While these data suggest a potential benefit of statins during acute coronary events , trials are necessary to determine the most appropriate use of statins in the treatment of acute coronary events . The Editors Data from r and omized clinical trials support the efficacy of lipid-lowering medications , particularly statins , in the primary and secondary prevention of coronary artery disease ( 1 - 3 ) . The benefits of statins , however , were not readily apparent until after several months of therapy , suggesting that the drugs ' lipid-lowering capabilities were largely responsible . In vitro work has suggested that statins may have an abundance of pleiotropic effects ( 4 ) . These include modulation of inflammation , inhibition of platelet function and thrombosis , and enhancement of endothelial cell function . The demonstrated ability of statins to immediately affect basic pathophysiologic mechanisms has result ed in increased interest in their potential role in the setting of acute coronary syndromes . The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering ( MIRACL ) trial found that early treatment with high-dose atorvastatin modestly reduced event rates of recurrent ischemia in statin-naive patients presenting with an acute coronary syndrome ( 5 ) . These observations , while intriguing , did not conclusively establish the role of statins in patients with acute coronary syndromes . In the MIRACL trial , the failure of statins to significantly affect more concrete trial end points ( for example , death or recurrent myocardial infa rct ion [ MI ] ) was disappointing . Whether this reflected a true lack of physiologic impact of early statin treatment or merely indicated that the study was underpowered to detect differences in these end points remains unclear . In a sub study using data from the Platelet Receptor Inhibition for Ischemic Syndrome Management ( PRISM ) trial in patients with acute coronary syndromes , patients already taking statins  had better short-term outcomes ( decreased risk for death or nonfatal MI ) than those not previously receiving statin therapy , unless statin therapy was discontinued in the hospital ( 6 ) . Initiation of statin therapy after the onset of an acute coronary syndrome appeared to be less effective than treatment with statins before symptom onset . Using data from the Global Registry of Acute Coronary Events ( GRACE ) project , a large , multinational , observational study of patients with acute coronary syndromes , we examined the association between previous statin therapy  , presentation characteristics of acute coronary syndromes , and hospital outcomes . We also examined the effect of early in-hospital statin therapy ( or withdrawal of statins ) on important hospital outcomes , including death or the development of recurrent MI or stroke . Methods Full details of the GRACE rationale and methods have been published elsewhere and are outlined below ( 7 - 9 ) . Site Selection The GRACE project is design ed to reflect an unbiased population of patients with acute coronary syndromes , regardless of geographic region . Currently , 94 hospitals located in 14 countries ( Argentina , Australia , Austria , Belgium , Brazil , Canada , France , Germany , Italy , New Zeal and , Pol and , Spain , the United Kingdom , and the United States ) are participating in this observational study . Patients entered in the registry must be at least 18 years of age and alive at the time of hospital presentation ; be admitted with an acute coronary syndrome as a presumptive diagnosis ( that is , have symptoms consistent with acute ischemia ) ; and have at least 1 of the following : electrocardiographic changes consistent with an acute coronary syndrome , serial increases in serum biochemical markers of cardiac necrosis , or documentation of coronary artery disease ( 7 - 9 ) . The qualifying acute coronary syndrome must not be precipitated by a significant noncardiovascular comorbid condition ( for example , trauma or surgery ) . To ensure the enrollment of an unbiased sample , the first 10 to 20 consecutive patients ( depending on each site 's patient volume ) are recruited from each site on a monthly basis . Where required , study investigators received approval from their local hospital ethics or institutional review board . Data Collection At each site , a trained coordinator collected data using a st and ardized case-report form . Data on demographic characteristics , medical history , presenting symptoms , duration of prehospital delay , biochemical and electrocardiographic findings , treatment practice s , and hospital outcome were collected . St and ardized definitions of all patient-related variables and clinical diagnoses were used . All cases were assigned to 1 of the following categories : ST-segment elevation MI , nonST-segment elevation MI , unstable angina , and other cardiac or noncardiac diagnoses that have been previously described ( 7 - 9 ) . St and ardized definitions were also used for selected hospital complications and outcomes . Patient Sample For the current study , patients who were subsequently found to have noncardiac or other cardiac ( nonacute coronary syndrome ) primary diagnoses and those who transferred into or out of GRACE registry hospitals were excluded from further consideration . Treatments defined as previous use were those taken by the patient on a long-term basis at home and within 7 days of the presenting event , based on the review of information contained in medical records and abstract ed by trained study physicians and nurses . Treatments received in the hospital ( within the first 24 hours or thereafter ) were categorized as within hospital . Agents prescribed for use after discharge from participating hospitals were categorized as at discharge . Patient treatment categories were defined according to the following groupings : no previous treatment with statins and no treatment with statins during hospitalization , no previous therapy with statins but statin therapy  instituted during hospitalization , previous therapy with statins and statin therapy continued during hospitalization , and previous  therapy with statins but statin therapy not continued during the index hospitalization . Statistical Analysis We used the chi-square tests for discrete variables to analyze differences in demographic and clinical characteristics , treatment practice s , clinical presentation ( ST-segment elevation vs. nonST-segment elevation , large infa rct [ creatine phosphokinase level > 2 times the upper limit of normal ] vs. small infa rct ) , subsequent diagnosis ( ST-segment elevation MI , nonST-segment elevation MI , unstable angina ) , and hospital complications ( death , congestive heart failure or pulmonary edema , cardiogenic shock , stroke , ventricular tachycardia or ventricular fibrillation , and cardiac arrest ) in relation to statin use . The Wilcoxon rank-sum test was used to analyze differences between respective comparison groups for continuous variables . While controlling for potentially confounding variables , we performed multivariate regression analyses to examine the association between previous statin therapy and hospital presentation ( ST-segment elevation vs. no ST-segment elevation , creatine phosphokinase level 2 times normal vs. creatine phosphokinase level < 2 times the upper limit of normal ) , as well as any association between previous or in-hospital statin therapy and hospital outcomes ( death , recurrent MI or MI after 24 hours , and stroke ) or a composite end point of all 3 outcomes . C and i date variables for inclusion in the regression models evaluating previous statin use and hospital presentation included patient age , sex , smoking status , diabetes , history of vascular disease ( previous MI , stroke , positive angiogram , peripheral vascular disease , percutaneous coronary intervention , or coronary artery bypass graft surgery ) , hypertension , hyperlipidemia , and previous therapies ( aspirin , angiotensin-converting enzyme [ ACE ] inhibitors , -blockers , and other lipid-lowering agents ) . C and i date variables for regression models evaluating previous or in-hospital statin use and hospital outcomes included all of the previously listed characteristics plus characteristics present at the time of hospital admission ( heart rate , systolic blood pressure , Killip class , ST-segment elevation or left bundle-branch block pattern , and positive cardiac enzymes ) and receipt of in-hospital therapies ( aspirin and other antiplatelet agents , -blockers , unfractionated heparin , low-molecular-weight heparin , glycoprotein IIb/IIIa inhibitors , cardiac catheterization , percutaneous coronary intervention , or coronary artery bypass graft surgery ) . C and i date variables possibly associated with the outcomes of interest ( P < 0.25 after univariate analysis ) were included in the multivariate models . Variables for which the P value exceeded 0.05 were eliminated in a stepwise fashion so that only those that had a statistically significant association with the outcome of interest were included in the final regression models . Because of their clinical relevance and potential importance , age , sex , and history of hyperlipidemia were retained in the final multivariable models for clinical outcomes regardless of statistical significance . Final models were evaluated for goodness of fit by the HosmerLemeshow test . Because between-hospital variation in use of statin treatment could be considerable and potentially affect our study results , we adjusted for hospital r and om effects on the observed outcomes . We used a generalized estimating equation modeling technique , assuming patients were repeated measures within each hospital . Variable Aims CD4+CD28null cells represent an aggressive and long-living T cell sub population , capable of infiltrating atheromatous plaque , leading to destabilisation and result ing in acute coronary syndromes ( ACS ) . The aim of this study was to evaluate whether statins decrease the number of circulating CD4+CD28null T cells by apoptosis in patients with ACS . Methods and results Patients with troponin-positive ACS ( n = 35 ) without cholesterol lowering drugs were r and omised to  placebo  ( n = 17 ) or rosuvastatin 20 mg ( n = 18 ) once daily for 6 weeks . CD4+CD28null T cell abundance ( > 1 % ) was distributed equally among the two groups at entry ( n = 10 per group ) . Within 72 h rosuvastatin treatment significantly reduced mean CD4+CD28null T cell numbers ( 37 × 106/L vs. placebo 122 × 106/L , n = 20 , P = 0.041 ) , IFN-γ production ( 62.6 vs. 101.5 % , P = 0.049 ) and increased apoptosis of these T cells ( 63.4 vs. 12.3 % , P < 0.001 ) . The intrinsic mitochondria-dependent pathway measured by the anti-apoptotic protein expression of B cell lymphoma 2 ( BCL-2 ) was significantly down-regulated ( mean fluorescence intensity 16.08 vs. placebo 43.34 , P < 0.001 ) . Conclusions The down-regulation of anti-apoptotic BCL-2 expression by statins  induces apoptosis in CD4+CD28null T cells . Targeting CD4+CD28null T cells in ACS statins could provide one further therapeutic strategy to prevent acute life-threatening coronary events PURPOSE The primary aim of the study was to investigate the effect of sinvastatin on plasma interleukin-6 ( IL-6 ) in patients with unstable angina pectoris ( UAP ) . METHODS Eighty-six patients with UAP were r and omized into simvastatin ( 40 mg/d for 4 weeks ) and the placebo group .  Plasma IL-6 was measured by ELISA . RESULTS There was a reduction in the plasma total cholesterol and LDL in the simvastatin group ( P < 0.01 ) . The simvastatin group also had better angina control than the placebo group ( post-treatment angina score , 0.72+/-0.59 vs 1.07+/-0.76 , P < 0.05 ) . Following treatment , the average left ventricular ejection fraction in the simvastatin group was higher than in the placebo group ( 0.54+/-0.06 vs 0.51+/-0.05 , P < 0.05 ) , whereas the plasma BNP levels were lower ( 16.8+/-6.6 vs 26.4+/-1.4 , P < 0.01 ) . Before treatment , there was no difference in the plasma levels of IL-6 between the simvastatin and the placebo groups ( P > 0.05 ) . Following treatment , the IL-6 levels in the simvastatin group were lower than in the placebo group ( 0.7+/-0.4 vs 1.2+/-0.4 pg/ml , P < 0.05 ) . CONCLUSIONS Short-term treatment with simvastatin reduces plasma IL-6 . The anti-inflammatory effect of simvastatin may contribute to its beneficial effects on the ventricular function and angina control BACKGROUND In patients with coronary heart disease and a broad range of cholesterol levels , cholesterol-lowering therapy reduces the risk of coronary events , but the effects on mortality from coronary heart disease and overall mortality have remained uncertain . METHODS In a double-blind , r and omized trial , we compared the effects of pravastatin ( 40 mg daily ) with those of a placebo over a mean follow-up period of 6.1 years in 9014 patients who were 31 to 75 years of age . The patients had a history of myocardial infa rct ion or hospitalization for unstable angina and initial plasma total cholesterol levels of 155 to 271 mg per deciliter . Both groups received advice on following a cholesterol-lowering diet . The primary study outcome was mortality from coronary heart disease . RESULTS Death from coronary heart disease occurred in 8.3 percent of the patients in the placebo group and 6.4 percent of those in the pravastatin group , a relative reduction in risk of 24 percent ( 95 percent confidence interval , 12 to 35 percent ; P<0.001 ) . Overall mortality was 14.1 percent in the placebo group and 11.0 percent in the pravastatin group ( relative reduction in risk , 22 percent ; 95 percent confidence interval , 13 to 31 percent ; P<0.001 ) . The incidence of all cardiovascular outcomes was consistently lower among patients assigned to receive pravastatin ; these outcomes included myocardial infa rct ion ( reduction in risk , 29 percent ; P<0.001 ) , death from coronary heart disease or nonfatal myocardial infa rct ion ( a 24 percent reduction in risk , P<0.001 ) , stroke ( a 19 percent reduction in risk , P=0.048 ) , and coronary revascularization ( a 20 percent reduction in risk , P<0.001 ) . The effects of treatment were similar for all predefined subgroups . There were no clinical ly significant adverse effects of treatment with pravastatin . CONCLUSIONS Pravastatin therapy reduced mortality from coronary heart disease and overall mortality , as compared with the rates in the placebo group , as well as the incidence of all prespecified cardiovascular events in patients with a history of myocardial infa rct ion or unstable angina who had a broad range of initial cholesterol levels AIMS To determine whether early statin therapy in acute myocardial infa rct ion has any effect on ventricular late potentials which are considered as a noninvasive tool for evaluation of arrhythmogenic substrate . METHODS AND RESULTS Study population consisted of prospect ively enrolled 72 patients presenting with acute myocardial infa rct ion ( < 6 h ) . Thirty-four of the patients were r and omized to pravastatin ( 40 mg/day ) on admission irrespective of lipid levels . All patients received thrombolytic therapy .  Signal-averaged ECG recordings were obtained serially prior to thrombolytic therapy , 48 h after and 10 days later . Late potentials were defined as positive if signal-averaged ECG met at least two of Gomes criteria : filtered total QRS duration > 114 ms , root mean square voltage of the last 40 ms of the QRS < 20 mV , or the duration of the terminal low ( < 40 mV ) amplitude signals > 38 ms . Changes observed in signal-averaged ECG recordings after thrombolysis were evaluated statistically with regard to statin usage . There were no significant differences between the clinical characteristics of the two r and omized groups . There was a significant decrease in the rates of late potentials between the first and third signal-averaged ECG recordings after thrombolytic therapy in pravastatin group . Pravastatin group also had lower incidence of ventricular arrhythmias compared with control group ( 26 vs. 63 % , P=0.021 ) . The in-hospital cardiovascular event rates were also lower in statin group . CONCLUSION Early use of pravastatin reduces the incidence of late potentials following thrombolytic therapy in acute myocardial infa rct ion . Statin therapy also seems to be reducing the incidence of in-hospital ventricular arrhythmias . These beneficial effects of statins might be explained through prevention of new myocardial ischemic episodes due to early plaque stabilization or regulation of endothelial and platelet functions BACKGROUND The mechanism underlying rapid , statin-induced event reduction in patients with an acute coronary syndrome ( ACS ) remains to be clarified . AIM The primary objective is to compare the efficacy of rosuvastatin 20 mg/day and atorvastatin 80 mg/day in reducing the apolipoprotein B/apolipoprotein A-1 ( apoB/apoA-1 ) ratio at three months , in ACS patients . Secondary objectives include a comparison of the effects of early-started rosuvastatin and placebo on inflammatory markers . METHODS This is a r and omized , double-blind , parallel-group study . Patients with non-ST-segment elevation ACS , symptom onset less than 48 h before admission , and for whom a percutaneous coronary intervention is planned , are eligible for inclusion and are r and omized into three groups ( G1 , G2 and G3 ) . The study comprises two double-blind periods . Period 1 starts at hospital admission and lasts until Day 0 ( discharge or less or equal to 6 days after admission ) ; patients in G1 receive one tablet of rosuvastatin 20 mg/day and patients in G2 and G3 receive one matching placebo tablet per day . Period 2 starts at Day 0 and lasts for three months ; patients in G1 continue to receive rosuvastatin 20 mg/day , patients in G2 receive rosuvastatin 20 mg/day and patients in G3 receive atorvastatin 80 mg/day . Recruitment of 1075 patients will ensure an 80 power to detect a 3 % difference in percentage change in the apoB/apoA-1 ratio and a 20 % difference in percentage change in high-sensitivity C-reactive protein . RESULTS Inclusion phase is complete ; results will be reported at a later date . CONCLUSION This is the first trial investigating the effect of statins on apolipoproteins in ACS patients Abstract Aims : This study tested the hypothesis that the addition of full-dose atorvastatin ( 80 mg/day ) to conventional medical treatment could reduce ischaemic recurrences after non-ST-elevation acute myocardial infa rct ion ( NSTE-AMI ) in patients with severe and diffuse coronary artery disease ( CAD ) not amenable to any form of mechanical revascularisation . Methods and results : The study was an open-label , r and omised , controlled , blinded end-point classification trial , employing the PROBE ( Prospect i ve Open Treatment and Blinded End Point Evaluation ) design . A total of 290 patients ( mean age 74.6 ± 9.6 years ) with NSTE-AMI and angiographic evidence of severe and diffuse CAD , not amenable to revascularisation by either coronary surgery or angioplasty , were r and omised to atorvastatin 80 mg/day  ( n = 144 ) or conventional medical treatment ( n = 146 ) . A primary end point event ( combination of cardiovascular death , non-fatal acute myocardial reinfa rct ion and disabling stroke within 12 months of r and omisation ) occurred in 16.0 % of patients treated with atorvastatin 80 mg/day and in 26.7 % of patients receiving conventional treatment ( HR 0.56 ; 95 % CI 0.33–0.93 , p = 0.027 ) . The study was not blinded . Consequently , a bias in the assessment of clinical outcome can not be completely excluded . Conclusions : In conclusion , when compared with a conventional treatment strategy , full-dose therapy with atorvastatin 80 mg/day provides greater protection against ischaemic recurrences after NSTE-AMI in patients with severe , diffuse , non-revascularisable CAD Patients with acute coronary syndrome are recommended for early aggressive low-density lipoprotein ( LDL ) cholesterol-lowering therapy . The LUNAR study compared the efficacy of rosuvastatin with that of atorvastatin in decreasing LDL cholesterol in patients with acute coronary syndrome . Adult patients with coronary artery disease who were hospitalized for an acute coronary syndrome within 48 hours of first symptoms were r and omized ( n = 825 ) to an open-label , once-daily treatment with rosuvastatin 20 mg ( RSV20 ) , rosuvastatin 40 mg ( RSV40 ) , or atorvastatin 80 mg ( ATV80 ) for 12 weeks . Patients were evaluated at weeks 2 , 6 , and 12 . The primary end point was treatment efficacy in lowering LDL cholesterol averaged over 6 to 12 weeks . Changes in other lipoproteins , including high-density lipoprotein ( HDL ) cholesterol , and safety were evaluated . Analysis of covariance was used to compare least squares mean differences between each rosuvastatin treatment arm and the atorvastatin arm . The efficacy of RSV40 in lowering LDL cholesterol was significantly greater than that of ATV80 ( 46.8 % vs 42.7 % decrease , p = 0.02 ) . LDL cholesterol lowering by RSV20 was similar to that by ATV80 . Increases in HDL cholesterol were significantly greater with RSV40 ( 11.9 % , p < 0.001 ) and RSV20 ( 9.7 % , p < 0.01 ) than with ATV80 ( 5.6 % ) . RSV40 was also significantly more effective than ATV80 in improving most other secondary efficacy variables , whereas the effects of RSV20 on these parameters were generally similar to those of ATV80 . All 3 treatments were generally well tolerated over 12 weeks . In conclusion , results from the LUNAR study show that RSV40 more effectively decreased LDL cholesterol , increased HDL cholesterol , and improved other blood lipid parameters than ATV80 in patients with acute coronary syndrome BACKGROUND We studied whether inflammation after myocardial infa rct ion ( MI ) is a risk factor for recurrent coronary events  and whether r and omized treatment with pravastatin reduces that risk . METHODS AND RESULTS A nested case-control design was used to compare C-reactive protein ( CRP ) and serum amyloid A ( SAA ) levels in prer and omization blood sample s from 391 participants in the Cholesterol and Recurrent Events ( CARE ) trial who subsequently developed recurrent nonfatal MI or a fatal coronary event ( cases ) and from an equal number of age- and sex-matched participants who remained free of these events during follow-up ( control subjects ) . Overall , CRP and SAA were higher among cases than control subjects ( for CRP P=0.05 ; for SAA P=0.006 ) such that those with levels in the highest quintile had a relative risk ( RR ) of recurrent events 75 % higher than those with levels in the lowest quintile ( for CRP RR= 1.77 , P=0.02 ; for SAA RR= 1.74 , P=0.02 ) . The study group with the highest risk was that with consistent evidence of inflammation ( elevation of both CRP and SAA ) who were r and omly assigned to placebo ( RR=2.81 , P=0.007 ) ; this risk estimate was greater than the product of the individual risks associated with inflammation or placebo assignment alone . In stratified analyses , the association between inflammation and risk was significant among those r and omized to placebo ( RR=2.11 , P=0.048 ) but was attenuated and nonsignificant among those r and omized to pravastatin ( RR=1.29 , P=0.5 ) . CONCLUSIONS Evidence of inflammation after MI is associated with increased risk of recurrent coronary events . Therapy with pravastatin may decrease this risk , an observation consistent with a nonlipid effect of this agent To compare the therapeutic effects of intensive versus moderate dosage of atorvastatin regimens in new-onset unstable angina with borderline lesions , 100 patients were r and omized to receive either 80 mg/d or 20 mg/d atorvastatin for 9 months . Clinical symptoms , lipid profiles , and coronary stenosis ( evaluated by coronary angiography and intravascular ultrasound ) were compared to their corresponding baselines within each group and between the 2 groups after 9 months of treatment . The results showed that ( 1 ) when compared to their corresponding baselines , both groups exhibited improvement in clinical symptoms , a significant decrease in total cholesterol , triglyceride , low-density lipoprotein cholesterol ( LDL-C ) , and high-sensitivity C-reactive protein ( hs-CRP ; P < .01 ) and a significant increase in high-density lipoprotein cholesterol ( HDL-C ) ; ( 2 ) the improvement in clinical symptoms and the decrease in LDL-C and hs-CRP were significantly greater ( P < .01 ) in the intensive-dose group than in the moderate-dose group ; ( 3 ) the mean plaque volume did not progress in the intensive-dose group but increased significantly ( P < .05 ) in the moderate-dose group . We conclude that compared to the moderate dose , the intensive-dose regimen significantly improves clinical symptoms , lowers LDL-C and hs-CRP , and halts the progression of borderline atherosclerotic plaques in patients with new-onset unstable angina Therapy with individual 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ( statins ) has been shown conclusively to diminish coronary event rates and mortality in both primary and secondary prevention . To date , scant attention has been paid to whether initiation of such regimens in the hospital phase of acute coronary syndromes might confer cardioprotective benefits . The purpose of this study was to determine the safety and tolerability of early initiation of statin therapy in patients with acute coronary syndromes . In this r and omised , double-blind , three-month , pilot study , 100 patients with acute myocardial infa rct ion or unstable angina and low-density lipoprotein cholesterol > 3.5 mmol/l were r and omly assigned to pravastatin 40 mg daily or placebo initiated within 48 hours of hospital admission . Pravastatin proved safe and well tolerated in these patients , who were well matched at baseline . No statistically significant differences in death , MI and drug-related adverse events were observed in the pravastatin group compared with control subjects . This pilot study shows that therapy with pravastatin early after an acute coronary event is safe and well tolerated . Larger , long-term studies are needed to confirm these findings We investigated the effects of atorvastatin on inflammation and cardiac events during the inpatient period and initial 6-month follow-up in acute coronary syndrome ( ACS ) patients with low low-density lipoprotein ( LDL ) cholesterol level . One hundred and twelve consecutive ACS patients with LDL cholesterol less than 100 mg/dl were included in the study ( mean 78.2 ± 12.3 mg/dl ) . While 70 r and omly selected patients received a dose of 40 mg atorvastatin within the first 24 h on top of their st and ard treatment as the atorvastatin group , the remaining 42 patients considered as the control group were given the st and ard treatment only , i.e. , without any lipid-lowering drug therapy .  Lipid profile , high-sensitivity C-reactive protein ( hsCRP ) , and plasma amyloid A ( SAA ) levels were measured in all patients within the first 24 h of chest pain , on the 5th day , and in the 6th month . During the inpatient period and subsequent 6-month follow-up , all episodes of angina , reinfa rct ion , revascularization , heart failure , rehospitalization , cardiac mortality , and total number of cardiac events were recorded . In the atorvastatin group , hsCRP and SAA values on the 5th day and in the 6th month compared to the first 24 h were significantly lower than those of the control group ( P < 0.0001 ) . Mean LDL cholesterol level was significantly decreased in the atorvastatin group ( 55.7 ± 17.7 mg/dl ) , but there was no significant change in the control group at the 6th month . The frequency of heart failure during the inpatient period and angina , unstable angina pectoris , heart failure , and revascularization in the first 6 months were also significantly reduced in the atorvastatin group . Atorvastatin started in the first 24 h reduces inflammation and improves the prognosis during both the inpatient period and the first 6 months of clinical follow-up in ACS patients with low LDL cholesterol levels BACKGROUND Many trials have shown that 3-hydroxy-3-methyl-glutaryl coenzyme A ( HMG-CoA ) reductase inhibitors reduce the incidence of cardiovascular events and mortality . One method of decreasing the incidence of cardiovascular events could be to reduce the progression of coronary atherosclerosis , and a recent study found that atorvastatin can cause coronary plaque to regress . To generalize this finding , using conventional HMG-CoA reductase inhibitors at many Japanese centers , r and omized trials of pitavastatin and atorvastatin will be conducted with patients with acute coronary syndrome ( ACS ) . METHODS AND RESULTS Patients with ACS who have undergone successful percutaneous coronary intervention under intravascular ultrasound guidance will be studied . They will be r and omly allocated to pitavastatin or atorvastatin groups and followed up for 8 - 12 months . The primary endpoint will be the percent change in coronary plaque volume , and secondary endpoints will include absolute changes in coronary plaque volume , serum lipid levels and inflammatory markers . The safety profile will also be evaluated . CONCLUSIONS This study will examine the ability of HMG-CoA reductase inhibitors to regress coronary plaque in Japanese patients with ACS and the findings should help to improve the prognosis of such patients and clarify the involved mechanisms BACKGROUND A number of experimental and clinical studies have demonstrated a cardioprotective effect of statins ; however , the effect of atorvastatin on cardiac function in patients with an acute myocardial infa rct ion ( AMI ) has not been established . METHODS AND RESULTS Thirty consecutive patients with an AMI ( 16 males and 14 females ) were enrolled . All the patients underwent successful percutaneous coronary intervention  in the early phase after the onset of an AMI . Patients with a total cholesterol level > 200mg/dL on admission ( n = 14 ) were assigned to the atorvastatin group . They began taking 10 mg of atorvastatin daily within 48 h after the onset of the AMI , while the other patients ( n = 16 ) did not receive atorvastatin and served as the control group . Echocardiography and blood sampling to measure brain natriuretic peptide ( BNP ) and atrial natriuretic peptide ( ANP ) levels were repeated on the 2nd day ( 2D ) , 3 weeks ( 3W ) , 12 weeks ( 12W ) , and 24 weeks ( 24W ) after the onset of the AMI . The percentage of patients with a high BNP level ( BNP > 20 pg/mL ) was significantly decreased from 2D to 24W in the atorvastatin group , but not in the control group ( 100 to 57 % in the atorvastatin group , p < 0.05 ; 100 to 80 % in the control group , n.s . ) . Similar results also occurred with respect to the ANP level ( ANP > 40 pg/mL ) ( 62 to 21 % in the atorvastatin group , p < 0.05 ; 57 to 40 % in the control group , n.s . ) . The left ventricular ejection fraction was significantly higher in the atorvastatin group than the control group at 3W ( 66.0 ± 7.8 % vs. 56.5 ± 11.8 % , p < 0.05 ) and 24W ( 67.5 ± 9.2 % vs. 59.7 ± 9.8 % , p < 0.05 ) . In the atorvastatin  group , the left ventricular systolic diameter was significantly decreased at 24W compared with that at 2D ( 37.1 ± 8.0 mm to 31.4 ± 6.5 mm , p < 0.05 ) . CONCLUSIONS Initiation of atorvastatin in the early phase of an AMI has beneficial effects on cardiac function , probably by improving left ventricular remodeling OBJECTIVE To find out whether the addition of fenofibrate to statin monotherapy produced any synergistic or additive beneficial effects in reducing risk factors , especially plasma fibrinogen , in patients with acute coronary syndrome ( ACS ) requiring percutaneous coronary interventions . METHODS A r and omized , non-blinded , prospect i ve study with parallel group design . One hundred two ACS patients who underwent angioplasty were r and omly assigned to atorvastatin ( 20 mg/day , n=25 ) , simvastatin ( 40 mg/day , n=27 ) , atorvastatin-fenofibrate ( 10 mg/day-200 mg/day ) combination ( n=25 ) or simvastatin-fenofibrate ( 20 mg/day-200 mg/day ) combination ( n=25 ) . The serum lipid profile and plasma fibrinogen were recorded before initiation of therapy and after three months of the respective treatments . RESULTS All patients already had desirable lipid levels as per the National Cholesterol Education Program - Adult Treatment Panel III guidelines . The addition of fenofibrate to statin monotherapy produced further benefits to the reduction in triglyceride and very low-density lipoprotein levels , and caused an increase in high-density lipoprotein levels . All the treatment groups showed a significant decrease in the plasma fibrinogen levels . Plasma fibrinogen did not correlate with study parameters such as age , body weight , hemo-dynamic characteristics and lipoprotein levels . Statin monotherapy as well as its combination with fenofibrate produced a significant decrease in the fibrinogen levels . CONCLUSIONS The addition of fenofibrate to statins seems to be beneficial in patients with ACS . Statins decreased plasma fibrinogen significantly , contrary to results from various reports , and the addition of fenofibrate further enhanced this reduction of the novel risk factor fibrinogen Pravastatin was administered to patients suffering an acute myocardial infa rct ion starting with a dose of 10 mg/day at day 3 and continuing with a dose of 20 mg/day up to a period of 3 months . The study was performed on the basis of a r and omized placebo-controlled double-blind trial . At the dosage used pravastatin significantly lowered the total cholesterol and LDL-cholesterol levels and increased the HDL-cholesterol levels compared to placebo . A prospect i ve clinical trial in order to examine the possible clinical relevance of these findings is recommended Aggressive treatment with high-dose atorvastatin reduces more effectively the incidence of cardiovascular events than moderate statin therapy . The mechanism of this benefit has not been fully eluci date d. In order to know the potential effects of statin treatment on the protein expression of circulating monocytes in acute coronary syndrome ( ACS ) patients , a proteomic analysis of these cells was carried out by 2-DE and MS . Twenty-five patients with non-ST-elevation acute coronary syndrome ( NSTEACS ) were r and omized , the fourth day after admission , to receive ATV 80 mg/dL ( n = 14 ) or conventional treatment ( CT ) ( n = 11 ) , for two months . Blood was withdrawn at the end of the treatment , and monocytes were extracted for proteomic analysis and their protein expression patterns determined . Age , sex , total cholesterol , LDL , HDL , triglycerides , body mass index , presence of hypertension , diabetes , and smoking status were not significantly different between the two groups of patients . The expression of 20 proteins was modified by intensive ATV . Among the most relevant results st and out the normalization by intensive ATV treatment of the expression of proteins that modulate inflammation and thrombosis such as protein disulfide isomerase ER60 ( PDI ) , Annexin I , and prohibitin , or that have other protective effects as HSP-70 . Thus , this approach shed light at the molecular level of the beneficial mechanisms of anti-atherothrombotic drugs BACKGROUND The incidence of no reflow phenomenon limits the clinical outcomes of percutaneous coronary intervention  ( PCI )  . This r and omized controlled study was design ed to evaluate the immediate protective effects of intensive statin pretreatment on myocardial perfusion and myocardial ischemic injury during PCI . METHODS Altogether 228 patients with acute coronary syndrome ( ACS ) were r and omly assigned to st and ard statin group ( SS group , n = 115 ) and intensive statin group ( IS group , n = 113 ) . Patients in the SS group received 20 mg simvastatin and patients in the IS group received 80 mg simvastatin for 7 days before PCI .  Thrombolysis in myocardial infa rct ion ( TIMI ) flow grade ( TFG ) , corrected TIMI frame count ( CTFC ) and TIMI myocardial perfusion grade ( TMPG ) of the intervened vessel were recorded before and after stent deployment . Creatine kinase ( CK ) isoenzyme MB , troponin I and plasma level of high sensitive-C reactive protein ( hs-CRP ) , P-selectin and intercellular adhesion molecule ( ICAM ) were measured before and 24 hours after the procedure . RESULTS The TFG after stent deployment was significantly improved with less TIMI 0 - 1 and more TIMI 3 blood flow in the IS group than in the SS group ( all P < 0.05 ) . Patients with no reflow phenomenon were less in the IS group ( P < 0.001 ) . The CTFC was lower in the IS group than in the SS group ( P < 0.001 ) . TMPG was also improved in the IS group than in the SS group ( P = 0.001 ) . Although PCI caused a significant increase in CK-MB 24 hours after the procedure , the elevated CK-MB value was lower in the IS group than in the SS group ( 18.74 + /- 8.41 vs 21.78 + /- 10.64 , P = 0.018 ) . Similar changes were also found in troponin I ( 0.99 + /- 1.07 in the IS group vs 1.47 + /- 1.54 in the SS group , P = 0.006 ) . CK-MB elevation occurred in 27.8 % ( 32/115 ) of the patients in the SS group vs 15.9 % ( 18/113 ) in the IS group ( P = 0.030 ) . Myocardial necrosis was detected in 4.4 % ( 5/115 ) of the patients in the SS group , whereas 0.9 % ( 1/113 ) in the IS group ( P = 0.341 ) . But no myocardial infa rct ion was found . Similarly , the patients with increased level of troponin I were much more in the SS group ( 36.5 % , 42/115 ) than in the IS group ( 19.5 % , 22/113 ) ( P = 0.04 ) . Among them , myocardial necrosis was detected in 13.0 % ( 15/115 ) of the patients in the SS group , while 4.4 % ( 5/113 ) in the IS group ( P = 0.021 ) . Myocardial infa rct ion was found in 4.4 % ( 5/115 ) of the patients in the SS group and 0.9 % ( 1/113 ) in the IS group ( P = 0.213 ) . CONCLUSIONS Intensive statin pretreatment for 7 days before PCI can further improve myocardial blood perfusion , protect the myocardium from ischemic injury . These effects are associated with the lowered levels of hs-CRP , P-selectin and ICAM Atherosclerosis is currently considered a chronic inflammatory disease of the vessel wall . Systemic markers of inflammation have been shown to be of significant prognostic relevance for assessing the risk of atherosclerotic disease progression (1)(2)(3)(4 ) . Previous data showed that proinflammatory markers , such as C-reactive protein ( CRP ) , play an important role in acute coronary events (5)(6)(7 ) and that decreased plasma concentrations of antiinflammatory cytokines , for example , interleukin-10 ( IL-10 ) were also associated with acute coronary syndrome ( ACS ) (8)(9)(10 ) . Statins , 3-hydroxy-3-methyglutaryl-coenzyme A reductase inhibitors , represent a well-established class of drugs that effectively lower serum cholesterol concentrations and are widely used for the treatment of cardiovascular disease (11)(12)(13 ) . In addition to their cholesterol-lowering activity , statins have been demonstrated to possess pleiotropic effects , including antiinflammatory effects (14)(15)(16)(17 ) . Results obtained in numerous investigations have suggested that administration of statins could modify concentrations of CRP and other proinflammatory cytokines with a concurrent decrease in cardiovascular events . However , the potential influence of statins on the antiinflammatory cytokine IL-10 in patients with ACS has not been investigated . In the present study , 42 patients with unstable angina ( UA ) were r and omly assigned immediately after admission to st and ard therapy  plus either 20 mg/day atorvastatin or placebo . The st and ard therapy included aspirin , beta-blockers , heparin/low – molecular-weight heparin , angiotensin-converting enzyme inhibitors , and oral nitrates . The protocol s of the study were approved by the Ethics Review Board of the Hospital , and all patients gave written , informed consent . The patients with UA presented with  ischemic chest pain  at rest in the absence of extracardiac cause with ST-segment depression ≥0.1 mV in 2 or more contiguous leads on 12-lead electrocardiograms at administration . Echocardiography was performed in all patients to exclude patients with an impaired left BACKGROUND The Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome ( JAPAN-ACS ) trial has found that early aggressive statin therapy in patients with acute coronary syndrome ( ACS ) significantly reduces the plaque volume ( PV ) of non-culprit coronary lesions . The purpose of the present study was to evaluate clinical factors that have an impact on plaque regression using statin therapy . METHODS AND RESULTS Serial intravascular ultrasound observations over 8 - 12 months were performed in 252 ACS patients receiving pitavastatin or atorvastatin .  Linear regression analysis identified the presence of diabetes mellitus ( DM ) and PV at baseline as inhibiting factors , and serum remnant-like particle-cholesterol level at baseline as a significant factor significantly affecting the degree of plaque regression . Significant correlation between % change of PV and low-density lipoprotein cholesterol ( LDL-C ) level was found in patients with DM ( n=73 , P<0.05 , r=0.4 ) , whereas there was no significant correlation between the 2 parameters in patients without DM ( n=178 ) . CONCLUSIONS The regression of coronary plaque induced by statin therapy after ACS was weaker in diabetic patients than their counterparts . Moreover , vigorous reduction of the LDL-C levels might induce a greater degree of plaque regression in ACS patients with DM OBJECTIVES To evaluate the effects of combined atorvastatin and probucol use on endothelial function in patients with acute coronary syndrome ( ACS ) . METHODS Thirty patients with ACS were r and omized to receive atorvastatin ( 20 mg/d ) and probucol ( 500 mg/d , combination group , n = 15 ) or atorvastatin ( 20 mg/d ) alone ( atorvastatin group ) within 24 h after admission for 4 weeks . Endothelium-dependent flow-mediated dilatation ( FMD ) and endothelium-independent sublingual nitroglycerin-mediated dilatation ( NMD ) as well as the levels of lipids and C-reactive protein were assessed at baseline , 1 week and 4 weeks after therapy . RESULTS Compared to baseline , the levels of total cholesterol , LDL-C and C-reactive protein were significantly reduced after 1 week and 4 weeks in both groups , FMD equally increased after 1 week in both groups ( atorvastatin group : 3.75 % + /- 0.78 % vs. 1.09 % + /- 0.44 % , combination group : 3.67 % + /- 0.36 % vs. 1.24 % + /- 0.37 % , P < 0.01 ) . Post 4 weeks therapy , FMD increase was significantly higher in combination group ( 3.67 % + /- 0.36 % at 1 week vs. 6.85 % + /- 0.64 % at 4 weeks , P < 0.01 ) than that in atorvastatin group ( 3.75 % + /- 0.78 % vs. 3.80 % + /- 0.31 % , P = 0.954 ) . NMD also equally and increased over 4 weeks in two groups ( P < 0.01 vs. baseline ) . There was no correlation between the change in FMD/NMD and the changes in lipids or C-reactive protein levels . CONCLUSIONS The combined atorvastatin and probucol therapy early after ACS is superior to atorvastatin alone on improving endothelial function Statins have been shown to prevent coronary artery disease and to preserve left ventricular function in dilated cardiomyopathy . We hypothesized that early use of statins would decrease cardiovascular events , including heart failure in patients with acute myocardial infa rct ion ( AMI ) . To examine the effect of statins in Japanese patients with AMI , a prospect i ve , r and omized , open-label trial was conducted in 486 patients with normal total cholesterol levels . Patients were r and omly assigned to receive any available statin ( n = 241 ) within 96 hours of AMI onset or no statin ( n = 245 ) and were followed for up to 24 months . The primary end point was a composite of cardiovascular death , nonfatal AMI , recurrent symptomatic myocardial ischemia , congestive heart failure , and stroke . Event rate for the primary end point was lower in the statin group than in the nonstatin group ( 6.1 % vs 11.4 % , p = 0.0433 ) . The statin group had a lower risk of congestive heart failure and symptomatic myocardial ischemia ( p = 0.0154 and 0.0264 , respectively ) . In conclusion , early lipid-lowering therapy with statins  decreases recurrent cardiovascular events , in particular , congestive heart failure Aims We sought to evaluate reports that rosuvastatin 10 mg is a more efficacious treatment of hyperlipidaemia than is simvastatin 40 mg , hoping to assess this issue in the previously unstudied context of acute myocardial infa rct ion . Methods and results The Secondary Prevention of Acute Coronary Events - Reduction of Cholesterol to Key European Targets ( SPACE ROCKET ) Trial was an investigator-led , open-label , blinded-endpoint , multicentre , r and omized , controlled trial assessing the proportion of patients , at 3 months , achieving European Society of Cardiology 2003 ( ESC-03 ) lipid targets of total cholesterol ( TC ) less than 4.5 mmol/l ( 174 mg/dl ) or low-density lipoprotein cholesterol ( LDLc ) less than 2.5 mmol/l ( 97 mg/dl ) . Of 1263 patients r and omized , 77.6 % simvastatin versus 79.9 % rosuvastatin achieved ESC-03 targets [ odds ratio ( OR ) : 1.16 ; 95 % confidence interval ( CI ) : 0.88–1.53 ; P = 0.29 ] . There were statistically significant differences for simvastatin versus rosuvastatin , respectively , for mean LDLc 2.03 mmol/l ( 78 mg/dl ) versus 1.94 mmol/l ( 75 mg/dl ; P = 0.009 ) and also mean TC 3.88 mmol/l ( 150 mg/dl ) versus 3.75 mmol/l ( 145 mg/dl ; P = 0.005 ) . A post-hoc analysis showed higher achievement of the new ESC , American Heart Association and American College of Cardiology optimal lipid target of LDLc less than 1.81 mmol/l ( 70 mg/dl ) with rosuvastatin ( 45.0 % ) compared with simvastatin ( 37.8 % ; OR : 1.37 ; 95 % CI : 1.09–1.72 ; P = 0.007 ) . The proportion of patients achieving the Fourth Joint Task Force European Guidelines ( 2007 ) of TC less than 4.0 mmol/l ( 155 mg/dl ) and LDLc less than 2.0 mmol/l ( 77 mg/dl ) was 38.7 % for simvastatin 40 mg and 47.7 % for rosuvastatin 10 mg ( OR : 1.48 ; 95 % CI : 1.18–1.86 ; P = 0.001 ) . Conclusion We observed no superiority of either treatment for the ESC-03 lipid targets . Rosuvastatin 10 mg lowered mean cholesterol more effectively than simvastatin and achieved better results for the latest , more stringent , ESC target CONTEXT Limited data are available evaluating how the timing and intensity of statin therapy following an acute coronary syndrome ( ACS ) event affect clinical outcome . OBJECTIVE To compare early initiation of an intensive statin regimen with delayed initiation of a less intensive regimen in patients with ACS . DESIGN , SETTING , AND PARTICIPANTS International , r and omized , double-blind trial of patients with ACS receiving 40 mg/d of simvastatin for 1 month followed by 80 mg/d thereafter ( n = 2265 ) compared with ACS patients receiving placebo for 4 months followed by 20 mg/d of simvastatin ( n = 2232 ) , who were enrolled in phase Z of the A to Z trial between December 29 , 1999 , and January 6 , 2003 . MAIN OUTCOME MEASURE The primary end point was a composite of cardiovascular death , nonfatal myocardial infa rct ion , readmission for ACS , and stroke . Follow-up was for at least 6 months and up to 24 months . RESULTS Among the patients in the placebo plus simvastatin group , the median low-density lipoprotein ( LDL ) cholesterol level achieved while taking placebo was 122 mg/dL ( 3.16 mmol/L ) at 1 month and was 77 mg/dL ( 1.99 mmol/L ) at 8 months while taking 20 mg/d of simvastatin . Among the patients in the simvastatin only group , the median LDL cholesterol level achieved at 1 month while taking 40 mg/d of simvastatin was 68 mg/dL ( 1.76 mmol/L ) and was 63 mg/dL ( 1.63 mmol/L ) at 8 months while taking 80 mg/d of simvastatin . A total of 343 patients ( 16.7 % ) in the placebo plus simvastatin group experienced the primary end point compared with 309 ( 14.4 % ) in the simvastatin only group ( 40 mg/80 mg ) ( hazard ratio [ HR ] , 0.89 ; 95 % confidence interval [ CI ] 0.76 - 1.04 ; P = .14 ) . Cardiovascular death occurred in 109 ( 5.4 % ) and 83 ( 4.1 % ) patients in the 2 groups ( HR , 0.75 ; 95 % CI , 0.57 - 1.00 ; P = .05 ) but no differences were observed in other individual components of the primary end point . No difference was evident during the first 4 months between the groups for the primary end point ( HR , 1.01 ; 95 % CI , 0.83 - 1.25 ; P = .89 ) , but from 4 months through the end of the study the primary end point was significantly reduced in the simvastatin only group ( HR , 0.75 ; 95 % CI , 0.60 - 0.95 ; P = .02 ) . Myopathy ( creatine kinase > 10 times the upper limit of normal associated with muscle symptoms ) occurred in 9 patients ( 0.4 % ) receiving simvastatin 80 mg/d , in no patients receiving lower doses of simvastatin , and in 1 patient receiving placebo ( P = .02 ) . CONCLUSIONS The trial did not achieve the prespecified end point . However , among patients with ACS , the early initiation of an aggressive simvastatin regimen result ed in a favorable trend toward reduction of major cardiovascular events The aim was to assess the impact of the short-term anti-inflammatory therapy on coronary endothelial function in non-ST-segment elevation acute coronary syndrome patients . In 30 patients , coronary endothelial function was assessed by acetylcholine test . Vessel response was calculated as a percent change of mean lumen diameter ( MLD ) . Then patients were r and omized into three groups : A ( n = 11 ) placebo , B ( n = 11 ) 80 mg atorvastatin , C ( n = 8) 80 mg atorvastatin and 25 mg rofecoxib . After 7 days control test was performed . Recovery of coronary endothelial function was calculated as delta in percent changes of MLD between Days 1 and 7 . On Day 1 , percent change of MLD between baseline and maximum acetylcholine did not differentiate the groups : -20 ± 3.5 % in A , -25 ± 3.9 % in B and -26 ± 3.7 % in C , P = .20 . On Day 7 , percentage changes in MLD were as follows : -21 ± 3.9 % in A , -15 ± 3.0 % in B and -10 ± 4.0 % in C , P=.002 . The delta in percentage change in MLD between Days 1 and 7 were as follows : -1 % in A , + 10 % in B and + 16 % in C , P = .02 . In conclusion , short-term , anti-inflammatory therapy with high-dose atorvastatin and selective cyclooxygenase-2 inhibitor improves coronary endothelial function within 7 days in non-ST-segment elevation acute coronary syndrome patients BACKGROUND The efficacy of statin drugs after an acute coronary event is now well established , but the evidence for statin use in the early treatment of acute coronary events remains unclear . METHODS We tested the effects of administering pravastatin within 24 hours of the onset of symptoms in patients with unstable angina , non-ST-segment elevation myocardial infa rct ion , or ST-segment elevation myocardial infa rct ion . Patient recruitment of 10,000 with 1200 end points was planned , but the trial was stopped early . A total of 3408 patients were r and omly assigned to treatment with pravastatin ( 1710 patients ) or matching placebo ( 1698 patients ) .  Treatment was continued for 4 weeks . The primary end point of the study was a composite of death , recurrence of myocardial infa rct ion , or readmission to hospital for unstable angina within 30 days of r and om assignment . RESULTS The primary end point occurred in 199 of patients allocated to pravastatin ( 11.6 % ) and in 211 patients allocated to placebo ( 12.4 % ) . A relative risk reduction of 6.4 % favored allocation to pravastatin but was not statistically significant ( 95 % CI , -13.2 % to 27.6 % ) . No adverse effects were seen . CONCLUSIONS We conclude that 20 to 40 mg of pravastatin can be safely administered within 24 hours of the onset of symptoms of an acute coronary event , with a favorable but not significant trend in outcome at 30 days compared with placebo BACKGROUND C-reactive protein ( CRP ) levels are associated with cardiovascular risk . We assessed the hypothesis that atorvastatin might have anti-inflammatory effects in acute coronary syndromes ( ACS ) as shown by CRP reduction . METHODS This study was a prospect i ve , r and omized , double-blind , placebo-controlled study of 90 consecutive patients admitted within 48 hours of onset of ACS with CRP levels > or = 1.4 mg/dL. Patients were assigned to atorvastatin 40 mg daily or placebo over 30 days . C-reactive protein levels , lipid profiles , serum fibrinogen , white cell count , and erythrocyte sedimentation rate were measured at entry , hospital discharge , and 1 month later . RESULTS Baseline clinical characteristics did not differ between  atorvastatin and placebo groups ( mean age 59.3 + /- 13.4 vs 61.1 + /- 11.5 , P = ns ) ; myocardial infa rct ion 52.3 % versus 67.4 % ( P = ns ) . In both groups , median baseline CRP levels were comparable ( 5.97 + /- 6.2 vs 4.64 + /- 4.2 mg/dL , P = ns ) . C-reactive protein levels were lower in the atorvastatin group versus control group at discharge ( 1.68 + /- 1.65 vs 4.12 + /- 4.18 mg/dL ) and at 30 days ( 0.50 + /- 0.71 vs 2.91 + /- 2.68 mg/dL , both P < .0001 ) . C-reactive protein levels significantly decreased from baseline to discharge and 1 month later in placebo and atorvastatin groups ( both P < .0001 ) ; however , the reduction was greater in the atorvastatin group ( 62 % vs 11 % at discharge [ P < .0001 ] ; 84 % vs 30 % at 1 month [ P < .0001 ] ) . In addition , atorvastatin was associated with a reduction in total and low-density lipoprotein cholesterol and erythrocyte sedimentation rate at discharge and at 30 days ( P < .0001 for all comparisons ) . No correlation was found between changes in CRP and cholesterol levels . CONCLUSIONS C-reactive protein levels in ACS were rapidly reduced with atorvastatin . These data provide evidence that statins have fast and early anti-inflammatory effects in addition to lipid-lowering effects in ACS Background : Patients who have had a coronary heart attack often go completely untreated for hypercholesterolemia . We investigated whether immediate initiation of lipid-lowering drugs during hospitalization for acute coronary events increases the proportion of correctly treated patients compared to referred treatment as recommended by current guidelines . Methods : This prospect i ve , multicenter study r and omized 57 hypercholesterolemic patients hospitalized for acute coronary events to immediate in-hospital initiation or to referred initiation of lipid-lowering drugs by primary care physicians 3 months after unsuccessful nutritional intervention .  Results : After 6 months , 53 patients were available for follow-up . More patients in the immediate initiation group ( 26/30 patients , 87 % ) were treated with lipid-lowering drugs than in the referred initiation-group ( 13/23 patients , 57 % , P=0.03 ) . Twenty-seven patients ( 87 % ) in the immediate initiation group versus 17 patients ( 65 % ) in the referred initiation group had a 10 % or greater decrease in total cholesterol or a 15 % or greater decrease in LDL-cholesterol ( P=0.18 ) . Although statistically not significant , there was a trend to improved lipid values in the immediate initiation group compared to the referred initiation group ( TC , -21.1 vs. -13.8 % ( P=0.08 ) ; LDL-C , -28.2 vs. -18.9 % ( P=0.13 ) ; HDL-C , + 10.8 vs. + 5 % ( P=0.44 ) ; TC/HDL-C ratio , -24.7 vs. -15.1 % ( P=0.22 ) ) , and the LDL-C/HDL-C ratio was -34.1 vs. -19.1 % ( P=0.04 , P = NS after Bonferroni correction ) . Conclusion : The immediate initiation of lipid-lowering drugs in hypercholesterolemic patients hospitalized for acute coronary events increases the rate of correctly treated patients and has the potential to improve lipid control BACKGROUND Lowering of LDL cholesterol reduces major vascular events , but whether more intensive therapy safely produces extra benefits is uncertain . We aim ed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk . METHODS We undertook a double-blind r and omised trial in 12,064 men and women aged 18 - 80 years with a history of myocardial infa rct ion . Participants were either currently on or had clear indication for statin therapy , and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not . R and omisation to either 80 mg or 20 mg simvastatin daily was done central ly using a minimisation algorithm . Participants were assessed at 2 , 4 , 8 , and 12 months after r and omisation and then every 6 months until final follow-up . The primary endpoint was major vascular events , defined as coronary death , myocardial infa rct ion , stroke , or arterial revascularisation . Analysis was by intention to treat . This study is registered , number IS RCT N74348595 . FINDINGS 6031 participants were allocated 80 mg simvastatin  daily , and 6033 allocated 20 mg simvastatin daily . During a mean follow-up of 6·7 ( SD 1·5 ) years , allocation to 80 mg simvastatin produced an average 0·35 ( SE 0·01 ) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg . Major vascular events occurred in 1477 ( 24·5 % ) participants allocated 80 mg simvastatin versus 1553 ( 25·7 % ) of those allocated 20 mg , corresponding to a 6 % proportional reduction ( risk ratio 0·94 , 95 % CI 0·88 - 1·01 ; p=0·10 ) . There were no apparent differences in numbers of haemorrhagic strokes ( 24 [ 0·4 % ] vs 25 [ 0·4 % ] ) or deaths attributed to vascular ( 565 [ 9·4 % ] vs 572 [ 9·5 % ] ) or non-vascular ( 399 [ 6·6 % ] vs 398 [ 6·6 % ] ) causes . Compared with two ( 0·03 % ) cases of myopathy in patients taking 20 mg simvastatin daily , there were 53 ( 0·9 % ) cases in the 80 mg group . INTERPRETATION The 6 % ( SE 3·5 % ) reduction in major vascular events with a further 0·35 mmol/L reduction in LDL cholesterol in our trial is consistent with previous trials . Myopathy was increased with 80 mg simvastatin daily , but intensive lowering of LDL cholesterol can be achieved safely with other regimens . FUNDING Merck ; The Clinical Trial Service Unit also receives funding from the UK Medical Research Council and the British Heart Foundation BACKGROUND The ESTABLISH trial found using volumetric intravascular ultrasound that atorvastatin therapy started early and continued for 6 months significantly reduced plaque volume in patients with acute coronary syndrome ( ACS ) . However , the benefits of early statin administration on long-term outcomes remain unclear . We therefore examined whether the early initiation of statin in patients with ACS improves long-term prognosis . METHODS AND RESULTS The Extended-ESTABLISH trial included 180 patients with ACS who underwent emergency percutaneous coronary intervention ( PCI ) . These patients were r and omized here to groups given either early intensive lipid-lowering therapy ( n=90 ; atorvastatin 20 mg/day ) or st and ard care ( control , n=90 ) within 48 h of events . Baseline characteristics between the two groups did not significantly differ at the time of ACS onset . Six months after PCI , all patients were treated with statins to achieve an LDL-C value of < 100 mg/dL. We compared the first occurrence of major adverse cardiac and cerebrovascular events ( MACCE ) . Prognostic data were fully documented during the entire follow-up period ( mean , 1538+/-707 days ) . Cumulative event-free survival was significantly higher in the atorvastatin , than in the control group ( p=0.041 ; log-rank test ) . Furthermore , by adjusting for vali date d prognosticators , early statin administration was identified as a good predictor of MACCE ( HR 0.46 , 95%CI 0.23 - 0.86 ; p=0.015 ) . CONCLUSIONS In-hospital initiation of statin therapy immediately after ACS conferred long-term benefits and 6 months of intensive lipid-lowering therapy improved long-term clinical outcomes after PCI in patients with ACS
target: Based on moderate quality evidence , due to concerns about risk of bias and imprecision , initiation of statin therapy within 14 days following ACS does not reduce death , myocardial infa rct ion , or stroke up to four months , but reduces the occurrence of unstable angina at four months following ACS .
  Serious side effects were rare
background: BACKGROUND The early period following the onset of acute coronary syndrome ( ACS ) represents a critical stage of coronary heart disease , with a high risk of recurrent events and deaths .
  The short-term effects of early treatment with statins on patient-relevant outcomes in patients suffering from ACS are unclear .
  This is an up date of a review previously published in 2011 .
  OBJECTIVES To assess the effects , both harms and benefits , of early administered statins in patients with ACS , in terms of mortality and cardiovascular events .