Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial. Use of the statins in patients after acute myocardial infarction: does evidence change practice? Randomized trial of atorvastatin for reduction of postoperative atrial fibrillation in patients undergoing cardiac surgery: results of the ARMYDA-3 (Atorvastatin for Reduction of MYocardial Dysrhythmia After cardiac surgery) study. The effects of atorvastatin on the occurrence of postoperative atrial fibrillation after off-pump coronary artery bypass grafting surgery.
This prospective, randomized, placebo-controlled, double-blind clinical trial was performed to analyze the effect of atorvastatin compared with placebo on the occurrence of a 6-month composite of cardiovascular events after vascular surgery. Cardiovascular complications are the most important cause of perioperative morbidity and mortality among patients undergoing vascular surgery. Statin therapy may reduce perioperative cardiac events through stabilization of coronary plaques.
                One hundred patients were randomly assigned to receive 20 mg atorvastatin or placebo once a day for 45 days, irrespective of their serum cholesterol concentration. Vascular surgery was performed on average 30 days after randomization, and patients were prospectively followed up over 6 months. The cardiovascular events studied were death from cardiac cause, nonfatal myocardial infarction, unstable angina, and stroke.
                Fifty patients received atorvastatin, and 50 received placebo. During the 6-month follow-up primary end points occurred in 17 patients, 4 in the atorvastatin group and 13 in the placebo group. The incidence of cardiac events was more than three times higher with placebo (26.0%) compared with atorvastatin (8.0%; P =.031). The risk for an event was compared between the groups with the Kaplan-Meier method, as event-free survival after vascular surgery. Patients given atorvastatin exhibited a significant decrease in the rate of cardiac events, compared with the placebo group, within 6 months after vascular surgery (P =.018).
                Short-term treatment with atorvastatin significantly reduces the incidence of major adverse cardiovascular events after vascular surgery. To compare the use of lipid-lowering agents in 42 628 elderly patients (aged > or =65 years) after acute myocardial infarction, before and after the publication of the Scandinavian Simvastatin Survival Study (4S), using the Ontario Myocardial Infarction Database.
                Multivariate regression models were created to estimate changes in the rate of statin use over time in monthly cohorts of elderly patients after acute myocardial infarction in Ontario from April 1, 1992, to March 31, 1997. Changes in the rate of statin use over time were estimated using patient and prescriber characteristics.
                We found a 3.6-fold significant increase in the monthly rate of statin use after the publication of 4S compared with before the publication of 4S (P<.001); specifically, the rate of increase in simvastatin and pravastatin sodium use was higher after the publication of 4S (P<.001 for each). Before the publication of 4S, the rate of increase in statin use in younger patients (aged 65-74 years) was 2.7 times higher than in older patients (aged > or =75 years) (P =.02), while after the publication of 4S, the rate of increase in statin use was only 1.8-fold higher in the younger group (P<.001). After the publication of 4S, there was a 1.6-fold higher rate of increase in statin use in male compared with female patients (P =.006). Also after the publication of 4S, specialists (cardiologists and internists) had a 2-fold higher rate of increased use of the statins than did generalists (P<.001).
                It is possible to shift practice if the evidence of benefit is strong, the intervention is easy to implement, and the intervention is marketed aggressively. Atrial fibrillation (AF) after cardiac surgery is associated with increased risk of complications, length of stay, and cost of care. Observational evidence suggests that patients who have undergone previous statin therapy have a lower incidence of postoperative AF. We tested this observation in a randomized, controlled trial.
                Two hundred patients undergoing elective cardiac surgery with cardiopulmonary bypass, without previous statin treatment or history of AF, were enrolled. Patients were randomized to atorvastatin (40 mg/d, n=101) or placebo (n=99) starting 7 days before operation. The primary end point was incidence of postoperative AF; secondary end points were length of stay, 30-day major adverse cardiac and cerebrovascular events, and postoperative C-reactive protein (CRP) variations. Atorvastatin significantly reduced the incidence of AF versus placebo (35% versus 57%, P=0.003). Accordingly, length of stay was longer in the placebo versus atorvastatin arm (6.9+/-1.4 versus 6.3+/-1.2 days, P=0.001). Peak CRP levels were lower in patients without AF (P=0.01), irrespective of randomization assignment. Multivariable analysis showed that atorvastatin treatment conferred a 61% reduction in risk of AF (odds ratio 0.39, 95% confidence interval 0.18 to 0.85, P=0.017), whereas high postoperative CRP levels were associated with increased risk (odds ratio 2.0, 95% confidence interval 1.2 to 7.0, P=0.01). The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms.
                Treatment with atorvastatin 40 mg/d, initiated 7 days before surgery, significantly reduces the incidence of postoperative AF after elective cardiac surgery with cardiopulmonary bypass and shortens hospital stay. These results may influence practice patterns with regard to adjuvant pharmacological therapy before cardiac surgery. Atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery is still the most common arrhythmic complication. This study evaluated whether pretreatment with atorvastatin protects against AF after off-pump CABG.
                One hundred twenty-four patients without a history of AF or previous statin use, who were scheduled to undergo elective off-pump CABG, were enrolled. Patients were randomized to control group (n = 62) or to atorvastatin group (n = 62) who were administered atorvastatin 20 mg/d for 3 days before the surgery. Primary outcome was the incidence of postoperative AF. Secondary outcomes were major adverse cardiac and cerebrovascular events, persistent AF at 1 month, and identification of the markers to predict inhospital postoperative AF.
                The incidence of AF was significantly lower in the atorvastatin group than in the control group (13% vs 27%, P = .04). The incidence of major adverse cardiac and cerebrovascular events and persistent AF at 1 month was similar in comparisons between the groups. Postoperative peak N-terminal pro-brain natriuretic peptide levels were significantly higher in the patients with AF (P = .03). Multivariate analysis identified pretreatment with atorvastatin as an independent factor associated with a significant reduction in postoperative AF (odds ratio 0.34, P = .04). Higher postoperative peak N-terminus pro-B-type natriuretic peptide levels were associated with the development of postoperative AF (odds ratio 1.02 per 100 pg/mL, P = .03).
                Pretreatment with atorvastatin significantly reduced the occurrence of postoperative AF after off-pump CABG.
Evidence was insufficient to allow review authors to conclude that statin use resulted in either a reduction or an increase in any of the outcomes examined. The existing body of evidence leaves questions about the benefits of perioperative use of statins for vascular surgery unanswered. Widespread use of statins in the target population means that it may now be difficult for researchers to undertake the large RCTs needed to demonstrate any effect on the incidence of postoperative cardiovascular events. However, participant-reported outcomes have been neglected and warrant further study.