Reduction in cardiovascular events after vascular surgery with atorvastatin: a randomized trial (original) (raw)
Related papers
American Heart Journal, 2017
Background: Preliminary evidence suggests statins may prevent major perioperative vascular complications. Methods: We randomized 648 statin-naïve patients who were scheduled for noncardiac surgery and were at risk of a major vascular complication. Patients were randomized to a loading dose of atorvastatin or placebo (80mg anytime within 18 hours before surgery), followed by a maintenance dose of 40mg (or placebo), started at least 12 hours after the surgery, and then 40mg/day (or placebo) for 7 days. The primary outcome was a composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery (MINS), and stroke at 30 days. Results: The primary outcome was observed in 54/326 (16.6%) of the atorvastatin group and 59/316 (18.7%) of the placebo group (HR 0.87; 95% CI 0.60 to 1.26; P=0.46). No significant effect was observed on the 30-day secondary outcomes of all-cause mortality (4.3% versus [vs.] 4.1%, respectively; HR 1.14; 95% CI 0.53 to 2.47; P=0.74), nonfatal myocardial infarction (3.4% vs. 4.4%, respectively; HR 0.76; 95% CI 0.35 to 1.68; P=0.50), MINS (13.2% vs. 16.5%; HR 0.79; 95% CI 0.53 to 1.19; P=0.26), and stroke (0.9% vs. 0%; P=0.25). Conclusion: In contrast to the prior observational and trial data, the LOAD trial has neutral results and did not demonstrate a reduction in major cardiovascular complications after a short-term perioperative course of statin in statin-naïve patients undergoing non-cardiac surgery. We demonstrated, however, that a large multicenter blinded perioperative statin trial for high risk statin-naïve patients is feasible, and should be done to definitely establish the efficacy and safety of statin in this patient population.
American Heart Journal, 2017
Background: Preliminary evidence suggests statins may prevent major perioperative vascular complications. Methods: We randomized 648 statin-naïve patients who were scheduled for noncardiac surgery and were at risk of a major vascular complication. Patients were randomized to a loading dose of atorvastatin or placebo (80mg anytime within 18 hours before surgery), followed by a maintenance dose of 40mg (or placebo), started at least 12 hours after the surgery, and then 40mg/day (or placebo) for 7 days. The primary outcome was a composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery (MINS), and stroke at 30 days. Results: The primary outcome was observed in 54/326 (16.6%) of the atorvastatin group and 59/316 (18.7%) of the placebo group (HR 0.87; 95% CI 0.60 to 1.26; P=0.46). No significant effect was observed on the 30-day secondary outcomes of all-cause mortality (4.3% versus [vs.] 4.1%, respectively; HR 1.14; 95% CI 0.53 to 2.47; P=0.74), nonfatal myocardial infarction (3.4% vs. 4.4%, respectively; HR 0.76; 95% CI 0.35 to 1.68; P=0.50), MINS (13.2% vs. 16.5%; HR 0.79; 95% CI 0.53 to 1.19; P=0.26), and stroke (0.9% vs. 0%; P=0.25). Conclusion: In contrast to the prior observational and trial data, the LOAD trial has neutral results and did not demonstrate a reduction in major cardiovascular complications after a short-term perioperative course of statin in statin-naïve patients undergoing non-cardiac surgery. We demonstrated, however, that a large multicenter blinded perioperative statin trial for high risk statin-naïve patients is feasible, and should be done to definitely establish the efficacy and safety of statin in this patient population.
2010
Background-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. Methods and Results-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, nϭ101) or placebo (nϭ99) 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%, Pϭ0.003). Accordingly, length of stay was longer in the placebo versus atorvastatin arm (6.9Ϯ1.4 versus 6.3Ϯ1.2 days, Pϭ0.001). Peak CRP levels were lower in patients without AF (Pϭ0.01), 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, Pϭ0.017), whereas high postoperative CRP levels were associated with increased risk (odds ratio 2.0, 95% confidence interval 1.2 to 7.0, Pϭ0.01). The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms. Conclusions-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. (Circulation. 2006;114:1455-1461.
Circulation, 2006
Background-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. Methods and Results-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, nϭ101) or placebo (nϭ99) 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%, Pϭ0.003). Accordingly, length of stay was longer in the placebo versus atorvastatin arm (6.9Ϯ1.4 versus 6.3Ϯ1.2 days, Pϭ0.001). Peak CRP levels were lower in patients without AF (Pϭ0.01), 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, Pϭ0.017), whereas high postoperative CRP levels were associated with increased risk (odds ratio 2.0, 95% confidence interval 1.2 to 7.0, Pϭ0.01). The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms. Conclusions-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. (Circulation. 2006;114:1455-1461.
Circulation, 2007
Background-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. Methods and Results-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, nϭ101) or placebo (nϭ99) 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%, Pϭ0.003). Accordingly, length of stay was longer in the placebo versus atorvastatin arm (6.9Ϯ1.4 versus 6.3Ϯ1.2 days, Pϭ0.001). Peak CRP levels were lower in patients without AF (Pϭ0.01), 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, Pϭ0.017), whereas high postoperative CRP levels were associated with increased risk (odds ratio 2.0, 95% confidence interval 1.2 to 7.0, Pϭ0.01). The incidence of major adverse cardiac and cerebrovascular events at 30 days was similar in the 2 arms. Conclusions-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. (Circulation. 2006;114:1455-1461.
The Journal of Thoracic and Cardiovascular Surgery, 2011
Objective: The preventative effect of statins on postoperative atrial fibrillation has been hypothesized. However, all studies to date have examined patients who did not receive statins before their further allocation to treatment or no treatment. Because guidelines recommend the routine use of statins in patients with coronary artery disease, we set out to examine the effect of intensive statin pretreatment versus continuation of usual statin dose on atrial fibrillation after cardiac surgery.
Journal of the American College of Cardiology, 2005
We sought to assess whether statins may decrease cardiac complications in patients undergoing noncardiac vascular surgery. BACKGROUND Cardiovascular complications account for considerable morbidity in patients undergoing noncardiac surgery. Statins decrease cardiac morbidity and mortality in patients with coronary disease, and the beneficial treatment effect is seen early, before any measurable increase in coronary artery diameter.
2005
We sought to assess whether statins may decrease cardiac complications in patients undergoing noncardiac vascular surgery. BACKGROUND Cardiovascular complications account for considerable morbidity in patients undergoing noncardiac surgery. Statins decrease cardiac morbidity and mortality in patients with coronary disease, and the beneficial treatment effect is seen early, before any measurable increase in coronary artery diameter. METHODS A retrospective study recorded patient characteristics, past medical history, and admission medications on all patients undergoing carotid endarterectomy, aortic surgery, or lower extremity revascularization over a two-year period (January 1999 to December 2000) at a tertiary referral center. Recorded perioperative complication outcomes included death, myocardial infarction, ischemia, congestive heart failure, and ventricular tachyarrhythmias occurring during the index hospitalization. Univariate and multivariate logistic regressions identified predictors of perioperative cardiac complications and medications that might confer a protective effect. RESULTS Complications occurred in 157 of 1,163 eligible hospitalizations and were significantly fewer in patients receiving statins (9.9%) than in those not receiving statins (16.5%, p ϭ 0.001). The difference was mostly accounted by myocardial ischemia and congestive heart failure. After adjusting for other significant predictors of perioperative complications (age, gender, type of surgery, emergent surgery, left ventricular dysfunction, and diabetes mellitus), statins still conferred a highly significant protective effect (odds ratio 0.52, p ϭ 0.001). The protective effect was similar across diverse patient subgroups and persisted after accounting for the likelihood of patients to have hypercholesterolemia by considering their propensity to use statins. CONCLUSIONS Use of statins was highly protective against perioperative cardiac complications in patients undergoing vascular surgery in this retrospective study.
Circulation, 2004
on behalf of the ARMYDA Investigators Background-Small myocardial infarctions after percutaneous coronary intervention have been associated with higher risk of cardiac events during follow-up. Observational studies have suggested that statins may lower the risk of procedural myocardial injury. The aim of our study was to confirm this hypothesis in a randomized study. Methods and Results-One hundred fifty-three patients with chronic stable angina without previous statin treatment were enrolled in the study. Patients scheduled for elective coronary intervention were randomized to atorvastatin (40 mg/d, nϭ76) or placebo (nϭ77) 7 days before the procedure. Creatine kinase-MB, troponin I, and myoglobin levels were measured at baseline and at 8 and 24 hours after the procedure. Detection of markers of myocardial injury above the upper normal limit was significantly lower in the statin group versus the placebo group: 12% versus 35% for creatine kinase-MB (Pϭ0.001), 20% versus 48% for troponin I (Pϭ0.0004), and 22% versus 51% for myoglobin (Pϭ0.0005). Myocardial infarction by creatine kinase-MB determination was detected after coronary intervention in 5% of patients in the statin group and in 18% of those in the placebo group (Pϭ0.025). Postprocedural peak levels of creatine kinase-MB (2.9Ϯ3 versus 7.5Ϯ18 ng/mL, Pϭ0.007), troponin I (0.09Ϯ0.2 versus 0.47Ϯ1.3 ng/mL, Pϭ0.0008), and myoglobin (58Ϯ36 versus 81Ϯ49 ng/mL, Pϭ0.0002) were also significantly lower in the statin than in the placebo group. Conclusions-Pretreatment with atorvastatin 40 mg/d for 7 days significantly reduces procedural myocardial injury in elective coronary intervention. These results may influence practice patterns with regard to adjuvant pharmacological therapy before percutaneous revascularization. (Circulation. 2004;110:674-678.)
Effects of atorvastatin on arterial endothelial function in coronary bypass surgery
European Journal of Cardio-Thoracic Surgery, 2005
Objective: Endothelial dysfunction represents a critical early component of organ injury following cardiopulmonary bypass. Recent studies demonstrate that the treatment with atorvastatin is associated with a significant improvement of endothelial function independently of its efficacy on cholesterol levels. Therefore, we investigated the effects of preoperative atorvastatin treatment on endothelium function after coronary surgery. Methods: Forty patients undergoing coronary surgery were randomized to treatment with atorvastatin (20 mg/die; N = 20) or placebo (N = 20) 3 weeks before surgery. Twenty normal patients served as control group. The flow-mediated dilations (FMD) of the brachial artery after both reactive hyperemia (endothelium dependent) and nitroglycerin administration (endothelium independent) were evaluated at baseline, at 48 h, and 5 days postoperatively. Results: At baseline, the endothelium-dependent FMD was significantly attenuated in coronary versus normal patients (normal 10.3 AE 1.8% vs coronary 4.1 AE 1.6%, p < 0.01). At 48 h postoperatively all patients exhibited a reduced FMD compared with baseline values: the endothelium-dependent dilatation showed a drop of 60.1 + 15% in the patients of the placebo group compared with 45.8 + 16.6% (p < 0.05) those in the atorvastatin group. At the univariate analysis, no significant correlation was found between serum levels of either total cholesterol or HDL cholesterol and FMD. The nitroglycerin-induced dilation was not significantly influenced by extracorporeal circulation as well as by atorvastatin treatment. Conclusions: The endothelial dysfunction following cardiopulmonary bypass is improved by the treatment with atorvastatin, by a mechanism unrelated to the drug efficacy of controlling serum cholesterol levels.