Atorvastatin for high-risk statin-naïve patients undergoing noncardiac surgery: The Lowering the Risk of Operative Complications Using Atorvastatin Loading Dose (LOAD) randomized trial

Background Preliminary evidence suggests that statinsmay prevent major perioperative vascular complications. Methods We randomized 648 statin-naive patients who were scheduled for noncardiac surgery and were at risk for a major vascular complication. Patients were randomized to a loading doseof atorvastatinor placebo (80 mg anytime within 18hours before surgery), followed by a maintenance doseof 40 mg (or placebo), started at least 12hours after the surgery, and then 40 mg/d (or placebo) for 7days. The primary outcome was a composite of all-cause mortality, nonfatal myocardial injury after noncardiac surgery, and stroke at 30days. Results The primary outcome was observed in 54 (16.6%) of 326 patients in the atorvastatingroup and 59 (18.7%) of 316 patients in the placebo group (hazard ratio [HR] 0.87, 95% CI 0.60-1.26, P =.46). No significant effect was observed on the 30-day secondary outcomes of all-cause mortality (4.3% vs 4.1%, respectively; HR 1.14, 95% CI 0.53-2.47, P =.74), nonfatal myocardial infarction (3.4% vs 4.4%, respectively; HR 0.76, 95% CI 0.35-1.68, P =.50), myocardial injury after noncardiac surgery (13.2% vs 16.5%; HR 0.79, 95% CI 0.53-1.19, 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 statinin statin-naive patients undergoing noncardiac surgery. We demonstrated, however, that a large multicenter blinded perioperative statintrial for high-risk statin-naive patients is feasible and should be done to definitely establish the efficacy and safety of statinin this patient population.