In 61 European centers over a period of 2.5 years, Oliver et al. conducted a double-blind, randomized, placebo-controlled trial (European Mivazerol Trial) with 2,854 patients to evaluate the effects of mivazerol on perioperative cardiac complications in those with and without a history of coronary heart disease (CHD). In this issue, the team reports analysis of data from 1,897 patient participants who had previous known CHD, 48% of whom had vascular surgery, 32% who had nonvascular thoracic or abdominal surgery, and 20% who underwent orthopedic procedures.
Patients with CHD were defined as those with a history of myocardial infarction; angiographically proven coronary artery stenosis of > 70% in at least one major vessel, or > 50% stenosis of the left main coronary artery; a positive stress echocardiography; or previous coronary artery bypass, among other factors. The study also included those at high risk for CHD. Patients were randomized immediately before drug or placebo infusion, which was started 20 min before induction of anesthesia and continued for 72 h postoperatively. The placebo was 0.9% saline, and the active drug was mivazerol hydrochloride, 4.0 μg/kg given during the first 10 min, followed by a constant rate infusion of 1.5 μg · kg−1· h−1. Hematologic and other biochemical measurements were obtained and analyzed. Electrocardiograms were recorded according to American Heart Association guidelines daily on postoperative days 1–7 and thereafter at 5-day intervals or whenever signs or symptoms indicated the need.
The primary endpoint was incidence of acute myocardial infarction or death up to 30 days after surgery; cause of death was ascertained and classified as either cardiac or noncardiac by the Endpoint Review Committee. Secondary endpoints included heart failure, life-threatening arrhythmia, and unstable angina. Overall, there was a 10.4% decrease in the primary endpoint (myocardial infarction or death) and a 37% reduction in deaths from all causes in the group receiving mivazerol. However, neither decrease was significant. Nevertheless, a subgroup analysis of 904 patients with known CHD undergoing vascular surgery revealed a significant beneficial trend toward fewer primary endpoints and fewer cardiac deaths in the group receiving mivazerol. According to the authors, a specifically designed second trial to confirm whether an α2-agonist such as mivazerol is truly beneficial in CHD patients undergoing vascular surgery is now warranted.