title: Fast assessment of stroke and transient ischaemic attack to prevent early recurrence (FASTER): a randomised controlled pilot trial The effect of aspirin, ticlopidine and their low‐dose combination on platelet aggregability in acute ischemic stroke: a short duration follow‐up study Clopidogrel versus aspirin and esomeprazole to prevent recurrent ulcer bleeding. Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients With Chronic Heart Failure: The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial Effect of platelet antigen polymorphism on platelet inhibition by aspirin, clopidogrel, or their combination. A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary artery stents. Effects of Combined Therapy With Clopidogrel and Acetylsalicylic Acid on Platelet Glycoprotein Expression and Aggregation Dual Antiplatelet Therapy With Clopidogrel and Aspirin in Symptomatic Carotid Stenosis Evaluated Using Doppler Embolic Signal Detection: The Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) Trial Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial A randomized trial comparing ticlopidine hydrochloride with indobufen for the prevention of stroke in high-risk patients (TISS Study). Ticlopidine Indobufen Stroke Study. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. European Stroke Prevention Study 2. Dipyridamole and acetylsalicylic acid in the secondary prevention of stroke Prasugrel versus clopidogrel in patients with acute coronary syndromes. Comparison of antiplatelet effects of aspirin, ticlopidine, or their combination after stent implantation. Hemostaseologic and hematologic parameters with aspirin and ticlopidine treatment in patients with cerebrovascular disease: a cross-over study. A randomized comparison of the effects of aspirin and clopidogrel on thrombotic risk factors and C-reactive protein following myocardial infarction: the CADET trial. [Aspirin vs ticlid and their combination in patients with acute myocardial infarction]. Efficacy of combination antiplatelet therapy and nicardipine for chronic cerebral infarction. Asymptomatic circulating cerebral emboli and cerebral blood flow velocity under aspirin and ticlopidine in patients with cerebrovascular disease. Effects of coadministration of aspirin or clopidogrel on exercise testing in patients with heart failure receiving angiotensin-converting enzyme inhibitors. Gastroduodenal tolerance of 75 mg clopidogrel versus 325 mg aspirin in healthy volunteers. A gastroscopic study. Unstable angina, stroke, myocardial infarction and death in aspirin non‐responders. A prospective, randomized trial. The ASCET (ASpirin non‐responsiveness and Clopidogrel Endpoint Trial) design Ticlopidine—Pentoxifylline Combination in the Treatment of Atherosclerosis and the Prevention of Cerebrovascular Accidents Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. Ticlopidine versus aspirin after myocardial infarction (STAMI) trial. Prevention of thromboembolism with ticlopidine shortly after valve repair or replacement with a bioprosthesis. Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke. [Comparative efficacy of tiklid and aspirin in patients with unstable angina]. The effect of clopidogrel, aspirin and both antiplatelet drugs on platelet function in patients with peripheral arterial disease
abstract: BACKGROUND Patients with transient ischaemic attack ( TIA ) or minor stroke are at high immediate risk of stroke . The optimum early treatment options for these patients are not known . METHODS Within 24 h of symptom onset , we r and omly assigned , in a factorial design , 392 patients with TIA or minor stroke to clopidogrel  ( 300 mg loading dose then 75 mg daily ; 198 patients ) or placebo ( 194 patients ) , and simvastatin ( 40 mg daily ; 199 patients ) or placebo ( 193 patients ) . All patients were also given aspirin and were followed for 90 days . Descriptive analyses were done by intention to treat . The primary outcome was total stroke ( ischaemic and haemorrhagic ) within 90 days . Safety outcomes included haemorrhage related to clopidogrel and myositis related to simvastatin . This study is registered as an International St and ard R and omised Controlled Trial ( number 35624812 ) and with Clinical Trials.gov ( NCT00109382 ) . FINDINGS The median time to stroke outcome was 1 day ( range 0 - 62 days ) . The trial was stopped early due to a failure to recruit patients at the prespecified minimum enrolment rate because of increased use of statins . 14 ( 7.1 % ) patients on clopidogrel had a stroke within 90 days compared with 21 ( 10.8 % ) patients on placebo ( risk ratio 0.7 [ 95 % CI 0.3 - 1.2 ] ; absolute risk reduction -3.8 % [ 95 % CI -9.4 to 1.9 ] ; p=0.19 ) . 21 ( 10.6 % ) patients on simvastatin had a stroke within 90 days compared with 14 ( 7.3 % ) patients on placebo ( risk ratio 1.3 [ 0.7 - 2.4 ] ; absolute risk increase 3.3 % [ -2.3 to 8.9 ] ; p=0.25 ) . The interaction between clopidogrel and simvastatin was not significant ( p=0.64 ) . Two patients on clopidogrel had intracranial haemorrhage compared with none on placebo ( absolute risk increase 1.0 % [ -0.4 to 2.4 ] ; p=0.5 ) . There was no difference between groups for the simvastatin safety outcomes . INTERPRETATION Immediately after TIA or minor stroke , patients are at high risk of stroke , which might be reduced by using clopidogrel in addition to aspirin . The haemorrhagic risks of the combination of aspirin and clopidogrel do not seem to offset this potential benefit . We were unable to provide evidence of benefit of simvastatin in this setting . This aggressive prevention approach merits further study We investigated the effects of aspirin ( 300 mg/d ) , ticlopidine ( 500 mg/d ) and their low‐dose combination ( aspirin 100 mg/d plus ticlopidine 250 mg/d ) on the platelet aggregability using the Wu and Hoak method . Each treatment group consisted of 25 patients with acute ischemic stroke .  Platelet aggregation ratios ( PAR ) were measured on the 1st ( before treatment ) , 10th and 90th days in the treatment groups and compared with those of 25 control cases . On the first day , comparison of PAR in each treatment group with the control was significant , while the differences between treatment groups were not significant . On the 90th day , differences of PAR between aspirin and control were significant , but differences between the other treatment groups and the control group were not significant , indicating a lower anti‐aggregant efficacy of aspirin BACKGROUND Concurrent therapy with a proton-pump inhibitor is a st and ard treatment for patients receiving aspirin who are at risk for ulcer . Current U.S. guidelines also recommend clopidrogel for patients who have major gastrointestinal intolerance of aspirin . We compared clopidogrel with aspirin plus esomeprazole for the prevention of recurrent bleeding from ulcers in high-risk patients . METHODS We studied patients who took aspirin to prevent vascular diseases and who presented with ulcer bleeding . After the ulcers had healed , we r and omly assigned patients who were negative for Helicobacter pylori to receive either 75 mg of clopidogrel daily plus esomeprazole placebo twice daily or 80 mg of aspirin daily plus 20 mg of esomeprazole twice daily for 12 months . The end point was recurrent ulcer bleeding . RESULTS We enrolled 320 patients ( 161 patients assigned to receive clopidogrel and 159 to receive aspirin plus esomeprazole ) .  Recurrent ulcer bleeding occurred in 13 patients receiving clopidogrel and 1 receiving aspirin plus esomeprazole . The cumulative incidence of recurrent bleeding during the 12-month period was 8.6 percent ( 95 percent confidence interval , 4.1 to 13.1 percent ) among patients who received clopidogrel and 0.7 percent ( 95 percent confidence interval , 0 to 2.0 percent ) among those who received aspirin plus esomeprazole ( difference , 7.9 percentage points ; 95 percent confidence interval for the difference , 3.4 to 12.4 ; P=0.001 ) . CONCLUSIONS Among patients with a history of aspirin-induced ulcer bleeding whose ulcers had healed before they received the study treatment , aspirin plus esomeprazole was superior to clopidogrel in the prevention of recurrent ulcer bleeding . Our finding does not support the current recommendation that patients with major gastrointestinal intolerance of aspirin be given clopidogrel Background — Chronic heart failure remains a major cause of mortality and morbidity . The role of antithrombotic therapy in patients with chronic heart failure has long been debated . The objective of this study was to determine the optimal antithrombotic agent for heart failure patients with reduced ejection fractions who are in sinus rhythm . Methods and Results — This prospect i ve , r and omized clinical trial of open-label warfarin ( target international normalized ratio of 2.5 to 3.0 ) and double-blind treatment with either aspirin ( 162 mg once daily ) or clopidogrel ( 75 mg once daily ) had a 30-month enrollment period and a minimum of 12 months of treatment . We enrolled 1587 men and women ≥18 years of age with symptomatic heart failure for at least 3 months who were in sinus rhythm and had left ventricular ejection fraction of ≤35 % . The primary outcome was the time to first occurrence of death , nonfatal myocardial infa rct ion , or nonfatal stroke . For the primary composite end point , the hazard ratios were as follows : for warfarin versus aspirin , 0.98 ( 95 % CI , 0.86 to 1.12 ; P=0.77 ) ; for clopidogrel versus aspirin , 1.08 ( 95 % CI , 0.83 to 1.40 ; P=0.57 ) ; and for warfarin versus clopidogrel , 0.89 ( 95 % CI , 0.68 to 1.16 ; P=0.39 ) . Warfarin was associated with fewer nonfatal strokes than aspirin or clopidogrel  . Hospitalization for worsening heart failure occurred in 116 ( 22.2 % ) , 97 ( 18.5 % ) , and 89 ( 16.5 % ) patients treated with aspirin , clopidogrel , and warfarin , respectively ( P=0.02 for warfarin versus aspirin ) . Conclusion — The primary outcome measure and the mortality data do not support the primary hypotheses that warfarin is superior to aspirin and that clopidogrel is superior to aspirin OBJECTIVES We studied the modifier effect of platelet antigen polymorphism ( PlA2 ) on platelet inhibition by acetylsalicylic acid ( ASA , i.e. , aspirin ) , clopidogrel , or their combination in patients with coronary heart disease . BACKGROUND Clopidogrel , when administered with ASA , was shown to significantly improve the outcome of patients with acute coronary syndromes compared with patients receiving only ASA . We have shown previously that the effect of ASA on platelets is modified by the glycoprotein IIIa single nucleotide polymorphism PlA2 . Hence , an important pharmacogenetic question remains whether the antiplatelet effect of clopidogrel is uniform for all patients or , like acetylsalicylic acid , more selective . METHODS Thirty PlA1/A1 and 30 PlA1/A2 patients were assigned r and omly to ASA 325 mg/day , clopidogrel 75 mg/day , or both . After 10 days , platelet function was studied . RESULTS Clopidogrel provided stronger platelet inhibition than ASA with adenosine diphosphate as the agonist , and combination therapy result ed in greater inhibition than either inhibitor used alone ( p < 0.0001 ) . The use of ASA result ed in greater inhibition compared with clopidogrel with epinephrine ( p < 0.0001 ) and collagen as agonists ( p < 0.0001 ) . With collagen as the agonist , platelets from PlA1/A2 donors were markedly and significantly less inhibited by ASA ( p = 0.005 ) . In contrast , with clopidogrel , no significant difference could be detected between inhibition of Pl(A1/A1 ) and Pl(A1/A2 ) platelets . CONCLUSIONS The combination of ASA and clopidogrel appears superior to either agent alone in inhibiting platelet function . Pl(A2 ) functions as an important modifier for platelet responsiveness to ASA but not to clopidogrel . These findings could have significant impact on the future design of pharmacogenetic antithrombotic strategies for patients with coronary heart disease OBJECTIVES The aim of the present study was to compare clopidogrel and ticlopidine after coronary stenting with regard to cardiovascular death during long-term follow-up . BACKGROUND R and omized trials comparing clopidogrel and ticlopidine with a restricted use of intravenous glycoprotein IIb/IIIa inhibition have reported a trend toward a higher incidence of thrombotic stent occlusion with clopidogrel at 30 days . METHODS After successful coronary stent implantation , 700 patients with 899 lesions were r and omly assigned to receive a four-week course of either 500 mg ticlopidine ( n = 345 ) or 75 mg clopidogrel ( n = 355 ) in addition to 100 mg aspirin .  Cardiovascular death was the primary end point and was recorded during a median follow-up period of 28 months . RESULTS Cardiovascular death occurred in eight patients with ticlopidine versus 26 patients with clopidogrel ( hazard ratio with ticlopidine compared with clopidogrel , 0.30 ; 95 % confidence interval [ CI ] , 0.14 to 0.66 ; p = 0.003 ) . After adjustment for co-variables , ticlopidine reduced the risk of cardiovascular death by 63 % compared with clopidogrel . The combined end point of cardiovascular death or nonfatal myocardial infa rct ion was present in 19 patients assigned ticlopidine , compared with 40 patients assigned clopidogrel ( hazard ratio , 0.45 ; p = 0.005 ) . The hazard ratio for all-cause mortality with ticlopidine as compared with clopidogrel was 0.30 ( 95 % CI , 0.14 to 0.64 ; p = 0.002 ) . CONCLUSIONS After the placement of coronary artery stents in unselected patients , ticlopidine was associated with a significantly lower mortality than clopidogrel . This raises concern about the current practice of substituting clopidogrel for ticlopidine after stenting and highlights the need for further long-term studies This study aim ed to compare the effects of clopidogrel , acetylsalicylic acid ( ASA ) , and the combination of both substances on platelet aggregation and expression of platelet membrane glycoproteins in patients with chronic coronary artery disease . We investigated platelet activation by flow cytometry and by platelet aggregation and disaggregation in 60 patients r and omly assigned to 3 treatment groups : ASA , clopidogrel , combination of clopidogrel and ASA , treated for 14 days . Adenosine diphosphate (ADP)–induced expression of P-selectin and of PAC-1 was significantly reduced after 2 wk of clopidogrel but not of ASA treatment . Treatment with clopidogrel reduced the ADP-induced platelet aggregation . The combination of clopidogrel and ASA did not increase the inhibition of platelet activation compared with clopidogrel alone . A significant increase in platelet disaggregation was observed with clopidogrel alone and was more pronounced with the combination of clopidogrel and ASA . ADP-induced platelet degranulation , activation of GPIIb/IIIa receptor , and aggregation in vivo are effectively inhibited by clopidogrel . The significantly increased disaggregation under clopidogrel and ASA suggests that the combined therapy may be superior to the monotherapy in patients with coronary artery disease and a high risk for vascular events Background — Evidence for efficacy of dual antiplatelet therapy in stroke is limited . Symptomatic carotid stenosis patients are at high risk of early recurrent stroke . In this group , asymptomatic microembolic signals ( MES ) , detected by transcranial Doppler ultrasound ( TCD ) , are markers of future stroke and transient ischemic attack ( TIA ) risk . They offer a surrogate marker to evaluate antiplatelet therapy , but no multicenter study has evaluated the feasibility of this approach . Methods and Results —Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis ( CARESS ) is a r and omized , double-blind study in subjects with recently symptomatic ≥50 % carotid stenosis . Patients were screened with TCD , and if MES were detected , they were r and omized to clopidogrel and aspirin or aspirin monotherapy . Repeated TCD recordings were made on days 2 and 7 . MES were detected in 110 of 230 patients by online analysis at baseline , of whom 107 were r and omized . Intention-to-treat analysis revealed a significant reduction in the primary end point : 43.8 % of dual-therapy patients were MES positive on day 7 , as compared with 72.7 % of monotherapy patients ( relative risk reduction 39.8 % ; 95 % CI , 13.8 to 58.0 ; P=0.0046 ) . The secondary end point of MES frequency per hour was reduced ( compared with baseline ) by 61.4 % ( 95 % CI , 31.6 to 78.2 ; P=0.0013 ) in the dual-therapy group at day 7 and by 61.6 % ( 95 % CI , 34.9 to 77.4 ; P=0.0005 ) on day 2 . There were 4 recurrent strokes and 7 TIAs in the monotherapy group versus no stroke and 4 TIAs in the dual-therapy group that were treatment emergent and ipsilateral to the qualifying carotid stenosis ; 2 additional ipsilateral TIAs occurred before treatment started . MES frequency was greater in the 17 patients with recurrent ipsilateral events compared with the 90 without ( mean±SD : 24.4±27.7 versus 8.9±11.5 per hour ; P=0.0003 ) . Conclusions —In patients with recently symptomatic carotid stenosis , combination therapy with clopidogrel and aspirin is more effective than aspirin alone in reducing asymptomatic embolization . Doppler MES detection is a feasible method to evaluate the efficacy of antiplatelet therapy in multicenter studies BACKGROUND Clopidogrel was superior to aspirin in patients with previous manifestations of atherothrombotic disease in the CAPRIE study and its benefit was amplified in some high-risk subgroups of patients . We aim ed to assess whether addition of aspirin to clopidogrel could have a greater benefit than clopidogrel alone in prevention of vascular events with potentially higher bleeding risk . METHODS We did a r and omised , double-blind , placebo-controlled trial to compare aspirin ( 75 mg/day ) with placebo in 7599 high-risk patients with recent ischaemic stroke or transient ischaemic attack and at least one additional vascular risk factor who were already receiving clopidogrel 75 mg/day . Duration of treatment and follow-up was 18 months . The primary endpoint was a composite of ischaemic stroke , myocardial infa rct ion , vascular death , or rehospitalisation for acute ischaemia ( including rehospitalisation for transient ischaemic attack , angina pectoris , or worsening of peripheral arterial disease ) . Analysis was by intention to treat , using logrank test and a Cox 's proportional-hazards model . FINDINGS 596 ( 15.7 % ) patients reached the primary endpoint in the group receiving aspirin and clopidogrel compared with 636 ( 16.7 % ) in the clopidogrel alone group ( relative risk reduction 6.4 % , [ 95 % CI -4.6 to 16.3 ] ; absolute risk reduction 1 % [ -0.6 to 2.7 ] ) . Life-threatening bleedings were higher in the group receiving aspirin and clopidogrel versus clopidogrel alone ( 96 [ 2.6 % ] vs 49 [ 1.3 % ] ; absolute risk increase 1.3 % [ 95 % CI 0.6 to 1.9 ] ) . Major bleedings were also increased in the group receiving aspirin and clopidogrel but no difference was recorded in mortality . INTERPRETATION Adding aspirin to clopidogrel in high-risk patients with recent ischaemic stroke or transient ischaemic attack is associated with a non-significant difference in reducing major vascular events . However , the risk of life-threatening or major bleeding is increased by the addition of aspirin Two treatments , based on either ticlopidine or indobufen at their optimal individual daily dose ( median dose : 250 and 200 mg/day , respectively ) , were compared in an open r and omized multicenter trial in patients at risk of cerebral ischemia ( men and women , aged 39 to 80 years , who had experienced in the month before entry into the study transient ischemic attack or amaurosis fugax or minor stroke ) . The total number of patients screened was 4033 ; 1632 were enrolled , 821 r and omized to ticlopidine , 811 to indobufen .  The overall frequency of the composite primary end-point ( stroke , myocardial infa rct ion , and death from any cause ) was 4.4 % . The ticlopidine-based regimen proved significantly better than the indobufen one in preventing the composite of fatal and non fatal events ( 49.6 % relative risk reduction ) , or death alone ( 54.4 % relative risk reduction ) . The two groups had similar percentages of adverse events ( 5.5 % and 6.4 % for ticlopidine and indobufen group , respectively ) with withdrawals because of adverse events in 3.4 % and 2.5 % ; gastrointestinal disorders and bleeding were more frequent in the indobufen group , whereas rash and abnormal liver function were more frequent in the ticlopidine one BACKGROUND Results of trials of aspirin and dipyridamole combined versus aspirin alone for the secondary prevention of  vascular events after ischaemic stroke of presumed arterial origin are inconsistent . Our aim was to resolve this uncertainty . METHODS We did a r and omised controlled trial in which we assigned patients to aspirin ( 30 - 325 mg daily ) with ( n=1363 ) or without ( n=1376 ) dipyridamole ( 200 mg twice daily ) within 6 months of a transient ischaemic attack or minor stroke of presumed arterial origin . Our primary outcome event was the composite of death from all vascular causes , non-fatal stroke , non-fatal myocardial infa rct ion , or major bleeding complication , whichever happened first . Treatment was open , but auditing of outcome events was blinded . Primary analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial ( number IS RCT N73824458 ) and with ( NCT00161070 ) . FINDINGS Mean follow-up was 3.5 years ( SD 2.0 ) . Median aspirin dose was 75 mg in both treatment groups ( range 30 - 325 ) ; extended-release dipyridamole was used by 83 % ( n=1131 ) of patients on the combination regimen . Primary outcome events arose in 173 ( 13 % ) patients on aspirin and dipyridamole and in 216 ( 16 % ) on aspirin alone ( hazard ratio 0.80 , 95 % CI 0.66 - 0.98 ; absolute risk reduction 1.0 % per year , 95 % CI 0.1 - 1.8 ) . Addition of the ESPRIT data to the meta- analysis of previous trials result ed in an overall risk ratio for the composite of vascular death , stroke , or myocardial infa rct ion of 0.82 ( 95 % CI 0.74 - 0.91 ) . Patients on aspirin and dipyridamole  discontinued trial medication more often than those on aspirin alone ( 470 vs 184 ) , mainly because of headache . INTERPRETATION The ESPRIT results , combined with the results of previous trials , provide sufficient evidence to prefer the combination regimen of aspirin plus dipyridamole over aspirin alone as antithrombotic therapy after cerebral ischaemia of arterial origin In 1988 , we undertook a r and omized , placebo-controlled , double-blind trial to investigate the safety and efficacy of low-dose acetylsalicylic acid ( ASA ) , modified-release dipyridamole , and the two agents in combination for secondary prevention of ischemic stroke . Patients with prior stroke or transient ischemic attack ( TIA ) were r and omized to treatment with ASA alone ( 50 mg daily ) , modified-release dipyridamole alone ( 400 mg daily ) , the two agents in a combined formulation , or placebo . Primary endpoints were stroke , death , and stroke or death together . TIA and other vascular events were secondary endpoints . Patients were followed on treatment for two years . Data from 6,602 patients were analysed . Factorial analysis demonstrated a highly significant effect for ASA and for dipyridamole in reducing the risk of stroke ( p < or = 0.001 ) and stroke or death combined ( p < 0.01 ) . In pairwise comparisons , stroke risk in comparison to placebo was reduced by 18 % with ASA alone ( p = 0.013 ) ; 16 % with dipyridamole alone ( p = 0.039 ) ; and 37 % with combination therapy ( p < 0.001 ) . Risk of stroke or death was reduced by 13 % with ASA alone ( p = 0.016 ) ; 15 % with dipyridamole alone ( p = 0.015 ) ; and 24 % with the combination ( p < 0.001 ) . The treatment had no statistically significant effect on the death rate alone . Factorial analysis also demonstrated a highly significant effect of ASA ( p < 0.001 ) and dipyridamole ( p < 0.01 ) for preventing TIA . The risk reduction for the combination was 36 % ( p < 0.001 ) in comparison with placebo .  Headache was the most common adverse event , occurring more frequently in dipyridamole-treated patients . All-site bleeding and gastrointestinal bleeding were significantly more common in patients who received ASA in comparison to placebo or dipyridamole . We conclude that ( 1 ) ASA 25 mg twice daily and dipyridamole , in a modified-release form , at a dose of 200 mg twice daily have each been shown to be equally effective for the secondary prevention of ischemic stroke and TIA ; ( 2 ) when co-prescribed the protective effects are additive , the combination being significantly more effective than either agent prescribed singly ; ( 3 ) low-dose ASA does not eliminate the propensity for induced bleeding BACKGROUND Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention . METHODS To compare prasugrel , a new thienopyridine , with clopidogrel , we r and omly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel ( a 60-mg loading dose and a 10-mg daily maintenance dose ) or clopidogrel ( a 300-mg loading dose and a 75-mg daily maintenance dose ) , for 6 to 15 months . The primary efficacy end point was death from cardiovascular causes , nonfatal myocardial infa rct ion , or nonfatal stroke . The key safety end point was major bleeding . RESULTS The primary efficacy end point occurred in 12.1 % of patients receiving clopidogrel and 9.9 % of patients receiving prasugrel ( hazard ratio for prasugrel vs. clopidogrel , 0.81 ; 95 % confidence interval [ CI ] , 0.73 to 0.90 ; P<0.001 ) . We also found significant reductions in the prasugrel group in the rates of myocardial infa rct ion ( 9.7 % for clopidogrel vs. 7.4 % for prasugrel ; P<0.001 ) , urgent target-vessel revascularization ( 3.7 % vs. 2.5 % ; P<0.001 ) , and stent thrombosis ( 2.4 % vs. 1.1 % ; P<0.001 ) . Major bleeding was observed in 2.4 % of patients receiving prasugrel and in 1.8 % of patients receiving clopidogrel ( hazard ratio , 1.32 ; 95 % CI , 1.03 to 1.68 ; P=0.03 ) . Also greater in the prasugrel group was the rate of life-threatening bleeding ( 1.4 % vs. 0.9 % ; P=0.01 ) , including nonfatal bleeding ( 1.1 % vs. 0.9 % ; hazard ratio , 1.25 ; P=0.23 ) and fatal bleeding ( 0.4 % vs. 0.1 % ; P=0.002 ) . CONCLUSIONS In patients with acute coronary syndromes with scheduled percutaneous coronary intervention , prasugrel therapy was associated with significantly reduced rates of ischemic events , including stent thrombosis , but with an increased risk of major bleeding , including fatal bleeding . Overall mortality did not differ significantly between treatment groups . ( Clinical Trials.gov number , NCT00097591 [ Clinical Trials.gov ] . BACKGROUND This study was performed to analyze the influence of either aspirin , ticlopidine , or their combination on platelet activation and aggregation parameters after stent implantation . METHODS AND RESULTS Sixty-one patients with successful implantation of a single Palmaz-Schatz stent in a native coronary artery were r and omly assigned to either group A ( aspirin 300 mg/d+ticlopidine 2X250 mg/d ) , group B ( ticlopidine 2X250 mg/d ) , or group C ( aspirin 300 mg/d ) . Platelet activation was evaluated on days 1 , 7 , and 14 by flow cytometry measurement of expression of CD62p ( p-selectin ) and the binding of fibrinogen to the platelet surface glycoprotein IIb/IIIa receptor . Platelet aggregation was induced by addition of ADP or collagen . Differences between treatment groups were compared by ANOVA . Between days 1 and 14 , we observed a significant decrease in collagen-induced platelet aggregation in group A ( 62.2+/-2.5 % versus 36.9+/-3.1 % ) , whereas an increase was seen in group B ( 58.3+/-2.5 % versus 67.7+/-3.2 % ) and no change was seen in group C ( P<.0001 ) . The ADP-induced aggregation declined significantly in group A ( 74.7+/-1.4 % versus 55.3+/-2.6 % ) , whereas a delayed reduction was seen in group B ( 72.0+/-3.0 % versus 52.6+/-4.2 % ) and no change was seen in group C ( P=.0017 ) . The CD62p expression declined significantly in groups A ( 68.2+/-2.7 % versus 41.3+/-2.7 % ) and B ( 64.8+/-2.9 % versus 39.3+/-3.5 % ) but not in group C ( P<.0001 ) . Moreover , the fibrinogen binding decreased significantly in group A ( 61.0+/-4.3 % versus 36.3+/-4.2 % ) and with delay in group B ( 58.3+/-2.2 % versus 39.4+/-3.0 % ) , whereas no alterations were seen in group C ( P=.012 ) . CONCLUSIONS Our results demonstrate synergistic and accelerated platelet inhibitory effects of ticlopidine plus aspirin in patients after stent implantation compared with a monotherapy with either ticlopidine or aspirin alone No direct comparisons of the effects of ticlopidine and aspirin on platelet aggregability , clotting parameters , and blood count are available in a cross-over study design in humans . We investigated 45 patients with cerebrovascular disease . Twenty-one patients received 300 mg aspirin once daily for 2 weeks and then for 2 more weeks received 250 mg ticlopidine twice daily . In 24 other patients , the scheme was reversed . ADP-induced aggregability was lower during ticlopidine treatment ; epinephrine- and collagen-induced aggregabilities were lower with aspirin treatment . Platelet counts were higher during ticlopidine than during aspirin treatment ( 199.6/ nl with aspirin , 213.0/nl with ticlop dine , p = 0.008 ) , probably reflecting less platelet activation and degradation and a longer platelet survival time induced by ticlopidine treatment A r and omized , double-blind multicenter trial-the Clopidogrel and Aspirin : Determination of the Effects on Thrombogenicity ( CADET ) trial-was carried out to compare the effects of clopidogrel vs. aspirin on thrombotic variables and C-reactive protein ( CRP ) , over a 6-month period of treatment , in patients with an acute myocardial infa rct ion within the previous 3 - 7 days , who were not scheduled for major surgery including coronary artery bypass grafting . Patients ( n = 184 ) were r and omly allocated to aspirin ( 75 mg day(-1 ) ) or clopidogrel ( 75 mg day(-1 ) ) . Blood sample s were taken at baseline and then at clinic visits at 1 , 3 and 6 months . By 1 month , clottable and immunonephelometric fibrinogen , D-dimer , von Willebr and factor , factor VIII and CRP were significantly ( P < 0.05 ) reduced from baseline values in both treatment groups ; as well as tissue plasminogen activator antigen in the aspirin group only . At 6 months , there were no differences between treatment groups ( P > 0.05 ) for any of the variables , whether or not potential confounding variables were adjusted for . Similarly , there were no differences between treatments in the difference between baseline and final values for any of the variables . Aspirin and clopidogrel were thus found to have similar effects on thrombotic variables and CRP in this patient population ADP-induced platelet aggregation was studied in 28 patients with myocardial infa rct ion r and omized , at admission , into three groups .  Conventional therapy with heparin and antianginal drugs was combined with aspirin ( 250 mg/day , n = 9 ) , tiklid ( 500 mg/day , n = 9 ) , tiklid ( 500 mg/day ) + aspirin ( 250 mg/day , n = 10 ) in group 1 , 2 and 3 , respectively . Tiklid diminished platelet aggregation more effectively than aspirin on the disease day 7 and 21 . Tiklid + aspirin combination suppresses platelet aggregation more than monotherapy with either of the drugs , provides insignificant attenuation of postinfa rct ion angina but is associated with a high risk of hemorrhagic complications To prevent recurrence of cerebral infa rct ion ( CI ) , the efficacy of antiplatelet therapy , when used in combination with a calcium antagonist , was examined . The study subjects were 57 chronic CI patients ( 40 men , 17 women ; mean age , 68.5 years ) who experienced either CI or its recurrence more than 3 months before the start of the study . They were r and omly allocated into one of the following four groups for the 8-week study ; group A -- ticlopidine hydrochloride 200 mg once daily and nicardipine hydrochloride 20 mg three times daily ( TID ) ; group B -- ticlopidine hydrochloride 200 mg once daily ; group C -- aspirin 81 mg once daily and nicardipine hydrochloride 20 mg TID ; or group D -- aspirin 81 mg once daily . Platelet aggregation was measured before treatment and 4 and 8 weeks after the initiation of each therapy by using adenosine diphosphate ( ADP ) ( 2 microM and 0.5 microM ) and collagen ( 2 micrograms/mL ) , and evaluated in terms of percent maximum platelet aggregation . Results showed significant suppression of 2.0 microM ADP platelet aggregation in groups A , B , and C. At 0.5-microM ADP , only groups A and B showed significant platelet aggregation suppression . All groups showed significant suppression of collagen platelet aggregation . In comparing single therapy with combination therapy , groups A and B were not significantly different from one another after 4 or 8 weeks in 2-microM ADP or collagen platelet aggregation suppression . In contrast , group C had significantly greater suppression of both 2-microM ADP and collagen aggregations compared with group D. In conclusion , nicardipine hydrochloride administration with aspirin may be a useful alternative therapy for the prevention of CI recurrence Aspirin and ticlopidine are two commonly used drugs in the prevention of cerebral embolic ischemic events . No direct comparisons in a cross-over design of the effects of ticlopidine and aspirin on asymptomatic circulating cerebral microemboli are available . We investigated 53 patients with cerebrovascular disease . Twenty-six patients were dosed for 2 weeks , 300 mg aspirin once daily and then for 2 weeks , 250 mg ticlopidine twice daily . In 27 other patients the scheme was reversed . Transcranial Doppler monitoring ( both middle cerebral arteries simultaneously for 1 h were performed at the end of the two weeks . The signal was recorded on digitalised audio tapes and analyzed blinded off-line . The number of embolic signals per hour and vessel was 15.7 under aspirin and 11.7 under ticlopidine ( difference not significant ) . The correlation between the number of emboli under the two medications was high . The highest number of embolic signals was found in high grade carotid stenosis . In patients with a low number of embolic signals , reproducibility was low . A minimum of 7 embolic signals in one treatment group is required for further therapeutic drug trials to allow reasonable comparisons . This study may help to plan further therapeutic trials using emboli detection Angiotensin-converting enzyme ( ACE ) inhibitors are effective drugs that have been shown to lower morbidity and mortality in patients with heart failure who have left ventricular systolic dysfunction . 1–3 Patients with congestive heart failure ( CHF ) often have indications for using both ACE inhibitors and antiplatelet agents . Various clinical trials have suggested that an adverse interaction exists from the combined use of aspirin and an ACE inhibitor in patients with CHF , but few studies have measured this effect directly . 3–12 The most compelling evidence of a potential adverse interaction between ACE inhibitors and aspirin stems from the Studies Of Left Ventricular Dysfunction ( SOLVD ) 1,10 and Cooperative New Sc and inavian Enalapril Survival Study II ( CONSENSUS II ) 11 trials . In SOLVD , although enalapril and aspirin when used alone were associated with lower mortality rates , retrospective analysis revealed that the addition of enalapril did not reduce mortality in patients already taking aspirin , and conversely , neither did the addition of aspirin in patients receiving enalapril . In a post hoc analysis of CONSENSUS II , aspirin and enalapril , when utilized alone , were associated with lower mortality rates . However , the relative risk of death at the end of the study was 1.23 ( 95 % confi dence interval [ CI ] 0.99 to 1.53 ) for patients taking aspirin and enalapril , and 0.86 ( 95 % CI 0.63 to 1.16 ) for patients taking enalapril without aspirin ( p 0.047 ) . Guazzi et al , 7 in a small prospect i ve study , measured maximal exercise oxygen uptake ( VO2max ) in patients with CHF , and demonstrated an adverse effect when ACE inhibitors were combined with aspirin , but not with ACE inhibitors alone . Therefore , we hypothesized that exercise duration and VO2max would not be attenuated by clopidogrel compared with aspirin in patients with CHF who are taking ACE inhibitors .  This study was approved by the institutional review board and all participants gave written consent before starting the study . We consecutively enrolled 18 patients with chronic stable CHF at our institution . Patient selection was made through chart review and phone interview of those patients who were likely to meet entry criteria . Inclusion criteria included patients between ages 19 and 80 years who were in stable New York Heart Association class II or III CHF due to ischemic or idiopathic dilated cardiomyopathy , with a documented left ventricular ejection fraction of 40 % within the past year . Patients had to be in sinus rhythm and on maintainance moderate-to-high dose ACE inhibitor therapy for 3 months . Exclusion criteria included a history of chronic lung disease , severe valvular heart disease , moderate-to-severe pulmonary hypertension , or a myocardial infa rct ion or cerebrovascular accident within the preceding 3 months . Patients with chronic stable angina or any other vascular , musculoskeletal , or metabolic condition precluding exercise testing were also excluded .  Antiplatelet therapy other than aspirin or clopidogrel within 4 weeks of the study or warfarin anticoagulation was not allowed . Exercise testing was performed using BACKGROUND Clopidogrel is a new antiplatelet agent that offers increased protection over aspirin in preventing vascular ischaemic events in patients with symptomatic atherosclerosis . In a large , r and omized , international study of clopidogrel and aspirin ( n = 19,185 patients )  clopidogrel was associated with a lower incidence of gastrointestinal adverse events , including gastrointestinal haemorrhage and hospitalizations because of gastrointestinal haemorrhage . The aim of the study was to determine whether macroscopic differences in the gastric mucosa between  aspirin- and clopidogrel-treated subjects could be detected by gastroscopy after short-term treatment . METHODS Thirty-six healthy volunteers were r and omized in a double-blind , double-dummy , parallel design , to 75 mg/day of clopidogrel or 325 mg/day of aspirin for 8 days . Gastroscopy was performed at base line before administration of study drug and directly after treatment completion . Gastroduodenal effects were measured in accordance with a modified Lanza scale . RESULTS At base line no difference between the groups was detected ( median Lanza score , 0.0 in both groups ) . At the end of treatment the aspirin group showed a median score of 7.5 , and the clopidogrel group showed an unchanged median score of 0.0 ( P < 0.001 ) . In the aspirin group 13 individuals reported 19 adverse events versus 8 individuals and 13 adverse events for clopidogrel , with approximately half of the adverse events being gastrointestinal in each group . No serious adverse events were reported . CONCLUSION In contrast to aspirin , short-term treatment with clopidogrel does not induce macroscopic changes in the gastroduodenal mucosa . The study results show that in patients without gastroduodenal disease  clopidogrel , but not aspirin , does not induce any gastroscopically evident erosions during short-term treatment Background —Aspirin is widely used as an antiplatelet drug in patients with coronary heart disease . Despite documented clinical benefit , many patients on aspirin  still experience severe cardiovascular events . Several laboratory reports have shown lack of platelet inhibition in 5–40 % of aspirin‐treated patients , and the term aspirin resistance has been introduced . The clinical relevance of these laboratory findings is , however , still unknown . New antiplatelet drugs have been developed , and the adenosin diphosphate ( ADP ) receptor inhibitor clopidogrel has at least the same efficacy as aspirin with an acceptable safety profile . Laboratory methods for determination of platelet reactivity and treatment efficacy have been complicated and time consuming . New method ologies , like the PFA‐100 ® system , have made such analyses more suitable for clinical use . Design —In the ASCET study , 1000 patients with documented coronary heart disease will be r and omized to either continued treatment with aspirin 160 mg/d or change to clopidogrel 75 mg/d after initial determination of their platelet reactivity while on aspirin treatment . Clinical endpoints will be recorded for at least 2 years and related to the initial aspirin response This r and omized , double-blind study on 79 patients reported the efficacy of ticlopidine – pentoxifylline combination in the treatment of  atherosclerosis  and the prevention of  cerebrovascular accidents .  Comparisons were made with aspirin – dipyridamole – buflomedil and buflomedil – placebo combinations as controls . Global symptoms , sensorimotor disorders and vertigo were improved in all treatment groups , although improvement tended to be more pronounced with ticlopidine – pentoxifylline . None of the groups showed any change in stenosis or vessel wall rigidity although ticlopidine – pentoxifylline  reduced flow irregularity . This combination therapy also normalized the direction of flow in the ophthalmic artery in 46.2 % of patients with retro grade flow prior to treatment , compared with 30.0 % following aspirin – dipyridamole – buflomedil and 28.6 % following buflomedil – placebo administration . Significantly fewer cerebrovascular accidents occurred after treatment with ticlopidine – pentoxifylline . In conclusion , ticlopidine – pentoxifylline  showed good therapeutic efficacy against atherosclerosis and a preventative effect against new cerebrovascular accidents . This therapy was well tolerated BACKGROUND Dual antiplatelet therapy with clopidogrel plus low-dose aspirin has not been studied in a broad population of patients at high risk for atherothrombotic events . METHODS We r and omly assigned 15,603 patients with either clinical ly evident cardiovascular disease or multiple risk factors to receive clopidogrel ( 75 mg per day ) plus low-dose aspirin ( 75 to 162 mg per day ) or placebo plus low-dose aspirin and followed them for a median of 28 months . The primary efficacy end point was a composite of myocardial infa rct ion , stroke , or death from cardiovascular causes . RESULTS The rate of the primary efficacy end point was 6.8 percent with clopidogrel plus aspirin and 7.3 percent with placebo plus aspirin ( relative risk , 0.93 ; 95 percent confidence interval , 0.83 to 1.05 ; P=0.22 ) . The respective rate of the principal secondary efficacy end point , which included hospitalizations for ischemic events , was 16.7 percent and 17.9 percent ( relative risk , 0.92 ; 95 percent confidence interval , 0.86 to 0.995 ; P=0.04 ) , and the rate of severe bleeding was 1.7 percent and 1.3 percent ( relative risk , 1.25 ; 95 percent confidence interval , 0.97 to 1.61 percent ; P=0.09 ) . The rate of the primary end point among patients with multiple risk factors was 6.6 percent with clopidogrel and 5.5 percent with placebo ( relative risk , 1.2 ; 95 percent confidence interval , 0.91 to 1.59 ; P=0.20 ) and the rate of death from cardiovascular causes also was higher with clopidogrel ( 3.9 percent vs. 2.2 percent , P=0.01 ) . In the subgroup with clinical ly evident atherothrombosis , the rate was 6.9 percent with clopidogrel and 7.9 percent with placebo ( relative risk , 0.88 ; 95 percent confidence interval , 0.77 to 0.998 ; P=0.046 ) . CONCLUSIONS In this trial , there was a suggestion of benefit with clopidogrel treatment in patients with symptomatic atherothrombosis and a suggestion of harm in patients with multiple risk factors . Overall , clopidogrel plus aspirin was not significantly more effective than aspirin alone in reducing the rate of myocardial infa rct ion , stroke , or death from cardiovascular causes . ( Clinical Trials.gov number , NCT00050817 . ) OBJECTIVES We sought to compare the efficacy of aspirin and ticlopidine in survivors of acute myocardial infa rct ion ( AMI ) treated with thrombolysis . BACKGROUND The role of ticlopidine in secondary prevention after AMI has not yet been explored . METHODS Of 4,696 patients with AMI treated with thrombolysis who were screened , 261 died in the hospital ( 5.6 % ) and 1,470 were enrolled in this r and omized , double-blind , multicenter trial and allocated to treatment with either aspirin ( 160 mg/day ) or ticlopidine ( 500 mg/day ) . The most frequent reasons for exclusion were refusal to give informed consent , planned myocardial revascularization , risk of noncompliance with study procedures , need for anticoagulant therapy and contraindications to the study treatments . The primary end point was the first occurrence of any of the following events during the six-month follow-up : fatal and nonfatal AMI , fatal and nonfatal stroke , angina with objective evidence of myocardial ischemia , vascular death or death due to any other cause . RESULTS The primary end point was recorded in 59 ( 8.0 % ) of the 736 aspirin-treated and 59 ( 8.0 % ) of the 734 ticlopidine-treated patients ( p = 0.966 ) . Vascular death was the first event in five patients taking aspirin and in six patients taking ticlopidine ( 0.7 % vs. 0.8 % ; p = NS ) ; nonfatal AMI in 18 and 8 ( 2.4 % vs. 1.1 % ; p = 0.049 ) ; nonfatal stroke in 3 and 4 ( 0.4 % vs. 0.5 % ; p = NS ) ; and angina in 33 and 40 ( 4.5 % vs. 5.4 % ; p = NS ) , respectively . The frequency of adverse reactions was not significantly different between the two groups . CONCLUSIONS No difference was found between the ticlopidine and aspirin groups in the rate of the primary combined end point of death , recurrent AMI , stroke and angina BACKGROUND AND AIMS OF THE STUDY This study investigated the efficacy of postoperative ticlopidine as antiplatelet therapy in patients shortly after heart valve repair or replacement . METHODS Between 1990 and 1995 , 235 consecutive patients underwent either valve repair ( n = 67 ) or replacement with a bioprosthesis ( n = 168 ) . The bioprostheses used were Carpentier-Edwards porcine or pericardial ( n = 158 ) valves , Prima stentless valves ( n = 3 ) and cryopreserved homografts ( n = 7 ) . Types of repair were aortic ( one ) , mitral annuloplasty with Carpentier ring ( 65 ) and tricuspid repair ( one ) . Mean patient age was 67 ( range : 16 to 83 ) years for valve replacement and 57 ( range : 32 to 74 ) years for repair ( p < 0.01 ) .  Atrial fibrillation  occurred in 34 % of patients . The hospital mortality rate was 11 % ( 26 patients ) . Of the 209 survivors , 137 were assigned to antiplatelet treatment with ticlopidine for the first three months of follow up . The other 72 received either oral anticoagulation ( coumadin ; n = 40 ) , aspirin ( n = 14 ) or no medication ( n = 18 ) . In 15 patients , ticlopidine treatment was interrupted due to diarrhea ( 13 cases ) , mild allergic reaction ( one ) or anemia ( one ) . The mean follow up was 3.2 years ( range : 1 month to 6 years ) ; cumulative follow up was 684 patient-years ( pt-yr ) and was complete in 96 % of cases . RESULTS There were two episodes of thromboembolism in the ticlopidine group at 1 month and 6 months respectively , with a linearized incidence of 0.5 % pt-yr . In the coumadin group there were four episodes of thromboembolism , three within the first three months of follow up . The linearized incidence was 3 % pt-yr ( p < 0.01 ) . There were three episodes of hemorrhage in the ticlopidine group in the first three months of follow up and one in the coumadin group . The linearized incidence was 0.75 % pt-yr . CONCLUSIONS Following heart valve repair or replacement with a bioprosthesis , the first three months is a high-risk period for thromboembolism . Ticlopidine seems to prevent this complication better than conventional therapy with oral anticoagulants . Nevertheless , hemorrhage continues to be a problem with ticlopidine therapy BACKGROUND Recurrent stroke is a frequent , disabling event after ischemic stroke . This study compared the efficacy and safety of two antiplatelet regimens -- aspirin plus extended-release dipyridamole ( ASA-ERDP ) versus clopidogrel . METHODS In this double-blind , 2-by-2 factorial trial , we r and omly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily . The primary outcome was first recurrence of stroke . The secondary outcome was a composite of stroke , myocardial infa rct ion , or death from vascular causes . Sequential statistical testing of noninferiority ( margin of 1.075 ) , followed by superiority testing , was planned . RESULTS A total of 20,332 patients were followed for a mean of 2.5 years .  Recurrent stroke occurred in 916 patients ( 9.0 % ) receiving ASA-ERDP and in 898 patients ( 8.8 % ) receiving clopidogrel ( hazard ratio , 1.01 ; 95 % confidence interval [ CI ] , 0.92 to 1.11 ) . The secondary outcome occurred in 1333 patients ( 13.1 % ) in each group ( hazard ratio for ASA-ERDP , 0.99 ; 95 % CI , 0.92 to 1.07 ) . There were more major hemorrhagic events among ASA-ERDP recipients ( 419 [ 4.1 % ] ) than among clopidogrel recipients ( 365 [ 3.6 % ] ) ( hazard ratio , 1.15 ; 95 % CI , 1.00 to 1.32 ) , including intracranial hemorrhage ( hazard ratio , 1.42 ; 95 % CI , 1.11 to 1.83 ) . The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups ( 1194 ASA-ERDP recipients [ 11.7 % ] , vs. 1156 clopidogrel recipients [ 11.4 % ] ; hazard ratio , 1.03 ; 95 % CI , 0.95 to 1.11 ) . CONCLUSIONS The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA-ERDP and with clopidogrel . There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke . ( Clinical Trials.gov number , NCT00153062 . AIM To evaluate effects of tiklid and aspirin on hemostasis , antithrombogenic activity of vascular wall in patients with unstable angina ( UA ) . MATERIAL AND METHODS An open r and omized trial enrolled 30 UA patients given tiklid ( n = 16 ) or aspirin ( n = 14 ) .  Hemostasis , platelet aggregation , antithrombogenic activity of the vascular wall were examined on the treatment day 1 and 20 . The response was assessed by the number of anginal attacks , dose of nitroglycerine , data of Holter monitoring . RESULTS Tiklid was more effective than aspirin in UA patients as it by the treatment day 20 lowered platelet aggregation more , higher elevated anticoagulation potential of the blood and vessels , and stronger activated fibrinolytic hemostasis . CONCLUSION Compared to aspirin , tiklid is more potent antiaggregant , has greater effect on antithrombogenic properties of the vascular wall Peripheral arterial disease ( PAD ) is associated with platelet hyperactivity . Aspirin and clopidogrel , two platelet inhibitors , act by different mechanisms . Aspirin inhibits thromboxane A2 synthesis and clopidogrel acts on the P2Y12 platelet ADP receptor . We evaluated the effect of clopidogrel ( 75 mg/day ) , aspirin ( 75 mg/day ) and then both drugs on several platelet function indices in patients with PAD ( n = 20 ) . There was a significant ( P = 0.0001 ) decrease in ADP-induced aggregation , after clopidogrel but not after taking aspirin . Clopidogrel plus aspirin significantly decreased spontaneous platelet aggregation ( SPA ) ( P = 0.01 to P = 0.002 ) but SPA was not significantly altered by either aspirin or clopidogrel monotherapy . Similarly , monotherapy did not inhibit serotonin (5HT)-induced aggregation but there was a significant inhibition ( P = 0.03 to P<0.02 ) after combination therapy . ADP ( 0.8 μM)-induced platelet shape change ( PSC ) was significantly inhibited by clopidogrel ( P = 0.004 ) or aspirin ( P = 0.01 ) . This was also true for 5HT-induced PSC  ( clopidogrel , P = 0.01 ; aspirin , P = 0.03 ) . Soluble P-selectin decreased significantly ( from 32 ± 24 to 25 ± 17 ng/ml , P = 0.04 ) with combination therapy . Plasma platelet-derived growth factor and intraplatelet 5HT levels were not altered by combination therapy . In PAD , clopidogrel is a more potent inhibitor of ADP-induced platelet activation than aspirin ; combination therapy is more effective than clopidogrel or aspirin monotherapy . These potentially clinical ly relevant findings should be evaluated in appropriately design ed trials
target: Compared with aspirin , thienopyridines significantly reduced gastrointestinal adverse effects .
  However , thienopyridines increased the odds of skin rash and diarrhoea , ticlopidine more than clopidogrel .
  Allocation to ticlopidine , but not clopidogrel , significantly increased the odds of neutropenia .
  The thienopyridine derivatives are at least as effective as aspirin in preventing serious vascular events in patients at high risk , and possibly somewhat more so .
  However , the size of any additional benefit is uncertain and could be negligible .
  Clopidogrel has a more favourable adverse effects profile than ticlopidine and so is the thienopyridine of choice .
background: BACKGROUND Aspirin is the most widely studied and prescribed antiplatelet agent for preventing serious vascular events , reducing the odds of such events among high vascular risk patients by about a quarter .
  Thienopyridine derivatives inhibit platelet activation by a different mechanism and so may be more effective .
  OBJECTIVES To determine the effectiveness and safety of thienopyridine derivatives ( ticlopidine and clopidogrel ) versus aspirin for preventing serious vascular events ( stroke , myocardial infa rct ion ( MI ) or vascular death ) in patients at high risk , and specifically in patients with a previous TIA or ischaemic stroke .