Effect of simvastatin on postoperative complications in patients undergoing one-lung ventilation during surgery: the Prevention HARP-2 randomised controlled trial

Rationale Surgeries that require one-lung ventilation have high rates of postoperative cardiopulmonary complications with associated morbidity and mortality. Statins may limit inflammation involved in the development of these complications. Objectives We tested the hypothesis that perioperative simvastatin use reduces postoperative cardiopulmonary complications, compared with placebo, in surgery requiring one-lung ventilation. Methods Randomised, double-blind, multicentre trial of simvastatin versus placebo in patients undergoing elective oesophagectomy, lobectomy or pneumonectomy at 15 sites throughout the UK. Planned sample size is 452 patients. Participants were randomised to either simvastatin 80 mg or placebo for 4 days preoperatively and up to 7 days postoperatively. Measurements The primary outcome measure was a composite endpoint of the incidence of acute respiratory distress syndrome, postoperative pulmonary complications, myocardial infarction and/or myocardial ischaemia during the first 7 days postoperatively or until hospital discharge. A modified intention-to-treat analysis excluded patients who did not receive the intervention preoperatively or proceed with the planned surgery. Main results 251 patients were randomised, 126 assigned to simvastatin and 125 to placebo, with 208 included in the modified intention-to-treat population. The trial was stopped early because of futility following recommendations from the data monitoring and ethics committee. The primary outcome occurred in 45/106 patients (42.5%) in the simvastatin group and 39/102 patients (38.2%) in the placebo group (OR 1.19 (95% CI 0.68 to 2.08); p=0.54). Secondary and safety outcomes were similar between the groups. Conclusion In patients undergoing one-lung ventilation, simvastatin did not reduce the incidence of postoperative cardiopulmonary complications. Trial registration number isrctn.org identifier, [ISRCTN48095567][1]. Data are available upon reasonable request. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN48095567