Abstract 13635: Atorvastatin for the Prevention of Major Vascular Events in Patients Undergoing Non-Cardiac Surgery: The LOAD-Pilot Randomized Clinical Trial

Abstract

Background: There is not a single established effective and safe intervention to prevent major perioperative vascular complications that commonly occur in the first 30 days after noncardiac surgery. Hypothesis: We evaluated the feasibility of a multicenter randomized controlled trial (RCT) testing the perioperative effects of statins. Methods: This is a double blind, placebo-controlled RCT testing a short course of atorvastatin 80mg before surgery, followed by 40mg 12 hours after surgery and then 40mg/day for 7 days in patients undergoing noncardiac surgery who were at risk of a major perioperative vascular complication. The primary outcome (major vascular events) was a composite of all-cause mortality, nonfatal myocardial infarction, MINS (myocardial injury after noncardiac surgery) without myocardial infarction and nonfatal stroke at 30 days after randomization. All analysis followed the intention-to-treat principle. Results: We enrolled 587 patients from 30 centers in Brazil. Mean age was 66.6 years, 37.1% were males, 22.0% had previous cardiovascular disease, 50.2% had diabetes and 89.7 % had hypertension. The majority of participants underwent general (35.9%), orthopedic (30.0%), gynecologic (8.4%), urologic (7.3%), and vascular (6.6%) surgery. A total of 51 out of 300 patients (17.0%) suffered a major vascular complication in the atorvastatin group compared to 49 out of 287 patients (17.1%) in the control group at 30 days (hazard ratio [HR] 1,02; 95% confidence interval (CI) 0.68 to 1.52; P = 0.93). No significant effect was observed on the 30-day secondary outcomes of death or myocardial infarction (8.0% versus [vs.] 7.7%, respectively; HR 0.94; 95% CI 0.52 to 1.70; P = 0.84), myocardial infarction (3.7% vs. 4.5%, respectively; HR 0.84; 95% CI 0.37 to 1.93; P = 0.68), MINS (14.0% vs.15.0%; HR 0.94; 95% CI 0.53 to 1.67; P = 0.84), and all-cause mortality (4.7% vs. 4.5%; HR 1.22; 95% CI 0.53 to 2.78; P = 0.64). Conclusions: The LOAD Trial confirms that a multicenter perioperative statin trial is feasible and highlights the need for large RCTs to establish effective and safe interventions. The study also suggests that effects of a perioperative statin on major vascular complications are, at best, moderate in size, questioning the robustness of prior data.