INTRODUCTION In vascular surgery, $-blockers are increasingly used to prevent peri-operative cardiac complications. This is a report of a RCT on the peri-operative use of metoprolol. METHODS After REB approval, patients undergoing abdominal aortic surgery, infra-inguinal or extraanatomical revascularization were recruited to a double-blind RCT of peri-operative metoprolol versus placebo. Consenting eligible patients were randomized to either IV/oral metoprolol or placebo 2 hours pre-op. Study medication was continued IV q6h or po bid until hospital discharge or maximum 5 days post-op. The primary outcome on an intent-to-treat basis was the 30-day post-op composite incidence of non-fatal MI; unstable angina; new CHF; new atrial or ventricular dysrhythmia requiring treatment; or cardiac death. RESULTS 497 patients consented and were randomized: 247 metoprolol and 250 placebo. The groups were balanced in demographics and pre-op co-morbidities. Early study drug discontinuation was 12% in placebo and 13% in metoprolol patients. One or more events in the primary outcome cluster occurred in 30 (12.0%) placebo and 25 (10.1%) metoprolol patients. The risk difference, -1.9% (CI -7.6% to 4.0%), was not significant (p=0.40). The observed effects in the primary cluster are shown (Table). Intra-operatively, more metoprolol patients had bradycardia requiring treatment (53/247 vs 19/250, p=0.00001) and hypotension requiring treatment (26/250 vs 84/247, p=0.0046). DISCUSSION This is the largest peri-operative $-blocker RCT completed to-date. An unblinded study 1 on 112 patients found a 10-fold reduction in MI and cardiac mortality. Our study was double-blinded and our patients were considered moderate/high risk. Another study reported 17-32% cardiovascular event rate2. It was under-powered to detect 30-day treatment effects although an effect beyond 6 months was noted. Our event rate was lower than previous reports, decreasing the study’s calculated power to detect 50% RRR from 80% to about 40%. In summary, our preliminary 30-day results did not support a clinically useful metoprolol effect in reducing the cardiac event rate in these vascular patients. The 6-month and longer-term follow-ups have yet to be completed.
BACKGROUND: Patients undergoing vascular surgery comprise the highest risk group for perioperative cardiac mortality and morbidity after noncardiac procedures. Many current guidelines recommend the use of beta-blockers in all patients undergoing vascular surgery. We report a trial of the perioperative administration of metoprolol and its effects on the incidence of cardiac complications at 30 days and 6 months after vascular surgery. METHODS: Patients undergoing abdominal aortic surgery and infrainguinal or axillofemoral revascularizations were recruited to a double-blind randomized controlled trial of perioperative metoprolol versus placebo. Patients were randomized to receive study medication, starting 2 hours preoperatively until hospital discharge or maximum of 5 days postoperatively. Primary outcome were postoperative 30-day composite incidence of nonfatal myocardial infarction, unstable angina, new congestive heart failure, new atrial or ventricular dysrhythmia requiring treatment, or cardiac death. RESULTS: Patients were randomized to receive either metoprolol (n = 246) or placebo (n = 250). Primary outcome events at 30 days postoperative occurred in 25 (10.2%) versus 30 (12.0%) (P = .57) in metoprolol and placebo groups, respectively (relative risk reduction 15.3%, 95% CI -38.3% to 48.2%). Observed effects at 6 months were not significantly different (P = .81) (relative risk reduction 6.2%, 95% CI% -58.4% to 43.8%). Intraoperative bradycardia requiring treatment was more frequent in the metoprolol group (53/246 vs 19/250, P = .00001), as was intraoperative hypotension requiring treatment (114/246 vs 84/250, P = .0045). CONCLUSION: Our results showed metoprolol was not effective in reducing the 30-day and 6-month postoperative cardiac event rates. Prophylactic use of perioperative beta-blockers in all vascular patients is not indicated.
INTRODUCTION In vascular surgery, $-blockers are increasingly used to prevent peri-operative cardiac complications. This is a report of a RCT on the peri-operative use of metoprolol. METHODS After REB approval, patients undergoing abdominal aortic surgery, infra-inguinal or extraanatomical revascularization were recruited to a double-blind RCT of peri-operative metoprolol versus placebo. Consenting eligible patients were randomized to either IV/oral metoprolol or placebo 2 hours pre-op. Study medication was continued IV q6h or po bid until hospital discharge or maximum 5 days post-op. The primary outcome on an intent-to-treat basis was the 30-day post-op composite incidence of non-fatal MI; unstable angina; new CHF; new atrial or ventricular dysrhythmia requiring treatment; or cardiac death. RESULTS 497 patients consented and were randomized: 247 metoprolol and 250 placebo. The groups were balanced in demographics and pre-op co-morbidities. Early study drug discontinuation was 12% in placebo and 13% in metoprolol patients. One or more events in the primary outcome cluster occurred in 30 (12.0%) placebo and 25 (10.1%) metoprolol patients. The risk difference, -1.9% (CI -7.6% to 4.0%), was not significant (p=0.40). The observed effects in the primary cluster are shown (Table). Intra-operatively, more metoprolol patients had bradycardia requiring treatment (53/247 vs 19/250, p=0.00001) and hypotension requiring treatment (26/250 vs 84/247, p=0.0046). DISCUSSION This is the largest peri-operative $-blocker RCT completed to-date. An unblinded study 1 on 112 patients found a 10-fold reduction in MI and cardiac mortality. Our study was double-blinded and our patients were considered moderate/high risk. Another study reported 17-32% cardiovascular event rate2. It was under-powered to detect 30-day treatment effects although an effect beyond 6 months was noted. Our event rate was lower than previous reports, decreasing the study’s calculated power to detect 50% RRR from 80% to about 40%. In summary, our preliminary 30-day results did not support a clinically useful metoprolol effect in reducing the cardiac event rate in these vascular patients. The 6-month and longer-term follow-ups have yet to be completed.
