Atorvastatin for High Risk Statin-Naïve Patients Undergoing Noncardiac Surgery: The LOAD Randomized Trial

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 (80 mg anytime within 18 hours before surgery), followed by a maintenance dose of 40 mg (or placebo), started at least 12 hours after the surgery, and then 40 mg/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 = .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 = .74), nonfatal myocardial infarction (3.4% vs. 4.4%, respectively; HR 0.76; 95% CI 0.35 to 1.68; P = .50), MINS (13.2% vs. 16.5%; HR 0.79; 95% CI 0.53 to 1.19; P = .26), and stroke (0.9% vs. 0%; P = .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. C linical trial registration: Clinicaltrials.gov Identifier: NCT01543555