BACKGROUND: Recent trials suggest that perioperative beta-blockade reduces the risk of cardiac events in patients with a risk of myocardial ischemia who are undergoing noncardiac surgery. Patients with diabetes mellitus are at a high-risk for postoperative cardiac morbidity and mortality. They may, therefore, benefit from perioperative beta-blockade.
METHODS: The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial is an investigator-initiated and -controlled, centrally randomized, double-blind, placebo-controlled, multicenter trial. We compared the effect of metoprolol with placebo on mortality and cardiovascular morbidity rates in patients with diabetes mellitus who were beta-blocker naive, >or=40 years old, and undergoing noncardiac surgery. The study drug was given during hospitalization for a maximum of 7 days beginning the evening before surgery. The primary outcome measure is the composite of all-cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure leading to hospitalization or discovered or aggravated during hospitalization. Follow-up involves re-examination of patients at 6 months and collection of mortality and morbidity data via linkage to public databases. The study was powered on the basis of an estimated 30% 1-year event rate in the placebo arm and a 33% relative risk reduction in the metoprolol arm. The median follow-up period was 18 months.
RESULTS: Enrollment started in July 2000 and ended in June 2002. A total of 921 patients were randomized, and 54% of these patients had known cardiac disease, hypertension, or both.
CONCLUSION: The results of this study may have implications for reduction of perioperative and postoperative risk in patients with diabetes mellitus who are undergoing major noncardiac surgery.
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
OBJECTIVES: To evaluate the long term effects of perioperative beta blockade on mortality and cardiac morbidity in patients with diabetes undergoing major non-cardiac surgery. DESIGN: Randomised placebo controlled and blinded multicentre trial. Analyses were by intention to treat. SETTING: University anaesthesia and surgical centres and one coordinating centre. PARTICIPANTS: 921 patients aged > 39 scheduled for major non-cardiac surgery. INTERVENTIONS: 100 mg metoprolol controlled and extended release or placebo administered from the day before surgery to a maximum of eight perioperative days. MAIN OUTCOME MEASURES: The composite primary outcome measure was time to all cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure. Secondary outcome measures were time to all cause mortality, cardiac mortality, and non-fatal cardiac morbidity. RESULTS: Mean duration of intervention was 4.6 days in the metoprolol group and 4.9 days in the placebo group. Metoprolol significantly reduced the mean heart rate by 11% (95% confidence interval 9% to 13%) and mean blood pressure by 3% (1% to 5%). The primary outcome occurred in 99 of 462 patients in the metoprolol group (21%) and 93 of 459 patients in the placebo group (20%) (hazard ratio 1.06, 0.80 to 1.41) during a median follow-up of 18 months (range 6-30). All cause mortality was 16% (74/462) in the metoprolol group and 16% (72/459) in the placebo group (1.03, 0.74 to 1.42). The difference in risk for the proportion of patients with serious adverse events was 2.4% (- 0.8% to 5.6%). CONCLUSIONS: Perioperative metoprolol did not significantly affect mortality and cardiac morbidity in these patients with diabetes. Confidence intervals, however, were wide, and the issue needs reassessment. TRIAL REGISTRATION: Current Controlled Trials ISRCTN58485613.
Recent trials suggest that perioperative beta-blockade reduces the risk of cardiac events in patients with a risk of myocardial ischemia who are undergoing noncardiac surgery. Patients with diabetes mellitus are at a high-risk for postoperative cardiac morbidity and mortality. They may, therefore, benefit from perioperative beta-blockade.
METHODS:
The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial is an investigator-initiated and -controlled, centrally randomized, double-blind, placebo-controlled, multicenter trial. We compared the effect of metoprolol with placebo on mortality and cardiovascular morbidity rates in patients with diabetes mellitus who were beta-blocker naive, >or=40 years old, and undergoing noncardiac surgery. The study drug was given during hospitalization for a maximum of 7 days beginning the evening before surgery. The primary outcome measure is the composite of all-cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure leading to hospitalization or discovered or aggravated during hospitalization. Follow-up involves re-examination of patients at 6 months and collection of mortality and morbidity data via linkage to public databases. The study was powered on the basis of an estimated 30% 1-year event rate in the placebo arm and a 33% relative risk reduction in the metoprolol arm. The median follow-up period was 18 months.
RESULTS:
Enrollment started in July 2000 and ended in June 2002. A total of 921 patients were randomized, and 54% of these patients had known cardiac disease, hypertension, or both.
CONCLUSION:
The results of this study may have implications for reduction of perioperative and postoperative risk in patients with diabetes mellitus who are undergoing major noncardiac surgery.
