Randomized, Blinded Trial on Perioperative Metoprolol Versus Placebo for Diabetic Patients Undergoing Non-Cardiac Surgery

Category Primary study
Year 2005
INTRODUCTION Trials suggest that perioperative -blockade reduces cardiac events in patients at risk of myocardial ischemia undergoing non-cardiac surgery. Diabetes confers high risk of cardiac morbidity and mortality. METHODS The DIabetic POstoperative Mortality and Morbidity Trial is an investigator-controlled, centrally randomized, placebo-controlled, blinded multicenter trial. We compared metoprolol 100 mg daily vs placebo on mortality and cardiovascular morbidity in -blocker naive diabetic patients above 39 years undergoing non-cardiac surgery. Metoprolol was given during hospitalization to a maximum of 7 days beginning the evening before surgery. Primary outcome was the composite of all-cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure. We aimed at 1000 patients (one-year incidence of primary outcome in the placebo arm30%, minimal relevant difference10%, power90%, alfa5%). RESULTS 2066 patients were eligible; 921 were randomized, 462 to metoprolol and 459 to placebo. Mean treatment duration was 4.6 vs 4.9 days. Day 1–7, 10–68% vs 5–59% received no intervention (contraindication or discharge), but heart rate (SD) was significantly lower in the metoprolol group (7513 vs 8414, P0.001). Median follow up was 18 months (range, 6 to 30). Primary outcome incidence was 99/462 (21%) in the metoprolol vs 93/459 (20%) in the placebo group (logrank test, P0.66). Multivariate Cox regression intention-to-treat analysis showed hazard ratio 1.10 (95% CI 0.82 to 1.46, P0.53) adjusting for age, gender, history of coronary heart disease, and malignant disease. The incidence of all-cause mortality was 74/462 (16%) vs 72/459 (16%) (logrank test, P0.88). Per protocol analyses (n733) and analyses of secondary outcomes showed similar results. Proportion of serious adverse events incidence was 7.1% in the metoprolol vs 5.2% in the placebo group (2 -test, P0.2). CONCLUSION Short-term perioperative metoprolol did not significantly affect mortality and cardiac morbidity or adverse events in diabetic patients undergoing non-cardiac surgery, but 95% CIs were wide. The dose, duration, drug, and intervention group need reconsideration. Larger, blinded, placebo-controlled trials are warranted. Imp
Epistemonikos ID: 5dd69f077be4570e6fe11f31eca13bcdea7a6f64
First added on: Apr 21, 2016