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. Reduced P-selectin in hearts pretreated with fluvastatin: a novel benefit for patients undergoing open heart surgery. Effect of preoperative atorvastatin therapy on atrial fibrillation following off-pump coronary artery bypass grafting. A randomized placebo controlled trial of the effect of preoperative statin use on matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in areas of low and peak wall stress in patients undergoing elective open repair of abdominal aortic aneurysm. Results of a randomized controlled trial on statin use in dialysis patients had no influence on statin prescription. Effects of atorvastatin on systemic inflammatory response after coronary bypass 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. P-selectin is an adhesion molecule that plays a role in the pathogenesis of atherosclerosis. The aim of this study was to assess whether or not the treatment with fluvastatin for 3 weeks preoperatively would reduce the levels of circulating P-selectin in patients with coronary heart disease undergoing coronary artery bypass grafting surgery (CABG).
                Forty-six patients referred to CABG operation were included in the study. The patients were randomized into two groups (1:1): one treated with fluvastatin (80 mg/day, fluvastatin group, n = 23), and the other one treated with placebo (placebo group, n = 23) for three weeks before surgery. All patients underwent CABG using CPB. Blood samples were collected at baseline (the day before surgery), before and after aortic cross-clamping (ACC), at postoperative 0 h (the end of surgical intervention), and at 4, 12, and 24 hours postoperatively. Concentrations of soluble P-selectin (sP-selectin) were analyzed.
                The sP-selectin values measured in the fluvastatin group were significantly lower than the values measured in the placebo group. There was less use of intraoperative inotropic agents in the fluvastatin group ( P < 0.015) and the difference in the length of ICU and hospital stay showed a significantly shorter stay for the fluvastatin group.
                Pretreatment with fluvastatin seemed to reduce P-selectin levels compared to patients given placebo, and hence, we think that pretreatment with a statin, fluvastatin in our study, might reduce the perioperative cardiac injury caused by cardiopulmonary bypass-induced inflammatory changes. We believe that routine preoperative use of fluvastatin should be carefully considered. Atrial fibrillation (AF) after coronary artery bypass grafting (CABG) is still the most common postoperative arrhythmic complication. Previous studies report that patients undergoing preoperative statin therapy had a lower incidence of postoperative AF. This study aimed to assess the effect of preoperative atorvastatin therapy on preventing AF following off-pump CABG in a randomized, controlled trial.
                The 140 consecutive patients undergoing elective off-pump CABG, without a history of AF or previous statin treatment, were enrolled and randomly assigned to a statin (atorvastatin 20 mg/day, n=71) or a control group (placebo, n=69) starting 7 days preoperatively. The primary endpoint was the occurrence of postoperative AF; secondary endpoints were major adverse in-hospital cardiac and cerebrovascular events and identification of variables predicting postoperative AF. Atorvastatin significantly reduced the incidence of postoperative AF and the postoperative peak C-reactive protein (CRP) level vs placebo (14% vs 34%, P=0.009; 126.5 +/-22.3 vs 145.2 +/-31.6 mg/L, P<0.0001). Logistic regression analysis showed preoperative atorvastatin treatment was an independent factor associated with a significant reduction in postoperative AF (odds ratio (OR) 0.219, P=0.005), whereas a high postoperative CRP level was associated with increased risk (OR 2.011, P=0.013).
                Administration of atorvastatin 20 mg/day, initiated 1 week before elective off-pump CABG and continued in the postoperative period, significantly decreases postoperative AF. A double-blind, randomized controlled trial was carried out to study the effects of statins on matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) in areas of peak and low abdominal aortic aneurysm (AAA) wall stress.
                A total of 40 patients undergoing elective open AAA repair were randomized to receive either atorvastatin 80 mg (n = 20) or placebo (n = 20) for 4 weeks preoperatively. Finite element analysis was used to determine AAA wall stress distribution. Full thickness aortic samples were obtained at surgery from areas of low and peak wall stress, snap-frozen, and stored at -80°C for subsequent MMP-2, -8, and -9 and TIMP-1 and -2 analyses. Statistical analysis was performed using SPSS 16.0 (SPSS Inc, Chicago, IL).
                Both groups were well matched (p > 0.05) regarding age, gender, comorbidities, and duration of hospital stay. There were no statistically significant differences in levels of MMPs and TIMPs between the statin and placebo group and between areas of low and peak AAA wall stress.
                The short-term use of statins is not associated in reducing levels of MMP 2, 8, and 9 and TIMP-1 and -2 in areas of low and peak wall stress in patients with AAA.
                Copyright © 2011. Published by Elsevier Inc. Randomized trials provide high-quality evidence for patient care. The Der Deutsche Diabetes Dialyse Studie (4D), a randomized study which demonstrated no benefit of statins among diabetic patients receiving hemodialysis, was published in July 2005. To determine effects of this study we conducted a retrospective, population-based, time series analysis with change-point regression to see if the rate of statin prescription to dialysis patients had been modified. We linked health administrative data for all diabetic hemodialysis patients living in Ontario, Canada, with similar characteristics to the 4D patient cohort. During the nearly 11-year period prior to study publication, the rate of statin use increased almost 14-fold, from 43 to 597 per 1000 patients. For 2.5 years after study publication, rather than diminish, statin use continued to rise to an absolute rate of 676 per 1000 patients. These temporal patterns in statin use closely mimicked trends in the diabetic population not receiving dialysis. The 4D trial had no impact on statin use when we restricted the analysis to incident statin prescriptions or expanded the characteristics of the dialysis patients considered for study. Thus, we found that publication of a large, expensive, randomized controlled trial in patients receiving hemodialysis had no immediate impact on clinical practice. The use of a common cardiovascular medication in this patient population appears to be influenced by other factors. Systemic inflammatory response occurs frequently after coronary artery bypass surgery, and it is strongly correlated with the risk of postoperative morbidity and mortality. Recent studies demonstrate that treatment with statin is associated with a significant and marked decrease in inflammation-associated variables such as the C-reactive protein, cytokines, and adhesion molecules. Therefore, we investigated the effects of preoperative atorvastatin treatment on systemic inflammatory response and perioperative morbidity after cardiopulmonary bypass.
                Double-blinded, placebo-controlled, randomized study.
                University hospital.
                Forty patients were randomized to treatment with atorvastatin (20 mg/day, group A, n=20) or placebo (group B, n=20) 3 wks before surgery.
                Three-week treatment by atorvastatin 20 mg/day.
                Postoperative serum levels of both interleukin-6 and interleukin-8 increased significantly over baseline, but the peak levels observed 4 hrs postoperatively were significantly lower in the atorvastatin group. In the same fashion, CD11b expression on neutrophils was significantly lower in the statin group at 4 and 24 hrs postoperatively. Finally, neutrophil-endothelial adhesion was significantly reduced in the statin patients compared with controls. The operation time, blood loss, need for inotropic support, intubation time, and length of intensive care unit or hospital stay did not differ significantly between the two groups. The systemic inflammatory response syndrome score on postoperative days 1 and 2 was comparable in both groups.
                Pretreatment with atorvastatin significantly reduces cytokine release and neutrophil adhesion to the venous endothelium in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.
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.