Effect of mivazerol on perioperative cardiac complications during non-cardiac surgery in patients with coronary heart disease - The European Mivazerol Trial (EMIT)

Background: Mivazerol(1) is a drug with alpha(2)-agonist properties that reduces post-ganglionic noradrenaline availability and spinal efferent sympathetic output. Methods: A double-blind randomized placebo-controlled trial was conducted in 61 European centers during a 2.5-yr period on 2,854 patients: 1,897 with coronary heart disease and 957 patients without overt coronary heart disease but classified as at high risk for it. The present analysis was restricted to those patients with previous known coronary heart disease of whom 48% had vascular surgery, 32% non-vascular thoracic or abdominal surgery, and 20% orthopedic surgery. Mivazerol or placebo were given intravenously from the induction of anesthesia for up to 72 h. Results: In the 1,897 patients with established coronary heart disease, mivazerol did not reduce the primary endpoint-the combination of myocardial infarction or death-or all-cause deaths significantly. A preplanned subgroup analysis of 904 patients with known coronary heart disease undergoing vascular surgery showed that there were fewer primary endpoints in those receiving mivazerol (risk ratio [RR], 0.67; 95% CL, 0.45-0.98; P = 0.037) and fewer cardiac deaths (6 of 454 ys. 18 of 450: RR, 0.33; 95% confidence limits, 0.15-0.82; P = 0.017), The all-cause death rate was also decreased (RR, 0.41; 95% CL, 0.18-0.91; P = 0.024), although there was no significant reduction in myocardial infarction. Conclusion: The alpha(2)-adrenergic agonist, mivazerol, did not alter the rates of myocardial infarction or cardiac death in patients with known coronary heart disease undergoing noncardiac surgery. However, it may have protected patients undergoing vascular surgery from further coronary events, and a specific study of such patients is now indicated.