Carvedilol Versus Metoprolol for the Prevention of Atrial Fibrillation After Off-Pump Coronary Bypass Surgery

Not Applicable

Completed

• Conditions: Coronary Disease; Atrial Fibrillation

• Registration Number: NCT00198614
• Lead Sponsor: Ministry of Health, Labour and Welfare, Japan

Brief Summary

Postoperative new-onset atrial fibrillation (AF) is the most common complication stemming from coronary artery bypass graft surgery, and is associated with increased early and late mortality risk. Standard guidelines recommend β blockers for the prevention of AF; however, no prospective study has compared the relative efficacy of β-blocking agents. We hypothesize that carvedilol, a non-selective adrenergic blocker with both anti-inflammatory and antioxidant properties, is more effective than metoprolol, a conventional β1-selective antagonist, in suppressing new-onset AF following off-pump coronary bypass surgery. We have designed the Carvedilol or Metoprolol Post-Revascularization Atrial Fibrillation Controlled Trial (COMPACT) to test our hypothesis in a multi-center, open-label, and randomized controlled trial.

Detailed Description

Occurring in 20% to 50% of patients, postoperative new-onset atrial fibrillation (AF) is the most common complication of coronary artery bypass graft (CABG) surgery. Reports have indicated that the occurrence of postoperative AF is associated with a prolonged stay in the hospital, readmission to the intensive care unit, stroke, and, consequently, increased overall costs. Moreover, recent results from both retrospective and prospective observational studies suggest that its associated early and late mortality risk is high. During the past decade, off-pump coronary bypass (OPCAB) surgery has gained widespread acceptance as an alternative to conventional on-pump CABG surgery, as avoiding cardiopulmonary bypass and myocardial ischemia-reperfusion is thought to significantly reduce postoperative systemic complications. Nevertheless, recent studies have revealed that OPCAB surgery does not reduce the incidence of postoperative AF, possibly because the consistent inflammatory differences between on-pump CABG and OPCAB surgery are present only at the beginning of the postoperative course, or partially because general surgical trauma may play a greater role. It has thus been anticipated that, as with on-pump CABG surgery, OPCAB surgery has high AF-related mortality and morbidity risks, and the prevention of new-onset AF following OPCAB surgery should significantly reduce the risk of these outcomes. To date, most reviews reflect a growing consensus in favor of the prophylactic administration of β blockers. In addition, the American College of Cardiology/American Heart Association guidelines for CABG surgery recommend β blockers for the prevention of AF. To the best of our knowledge, however, no prospective study has evaluated the merits of a specific β-blocking agent or concluded that each of these agents is equally efficacious.

Carvedilol, a non-selective beta adrenergic blocking agent approved for use in heart failure cases, has a number of ancillary activities including anti-inflammatory and antioxidant properties. Although the exact pathophysiology of new-onset AF following OPCAB surgery has not yet been elucidated, recent reports suggest that markers of inflammation and oxidative injury are elevated in patients with non-surgical AF. In addition, clinical studies indicate that, unlike the β1-selective agent metoprolol, carvedilol has incremental benefits for AF management in heart failure patients. The anti-inflammatory and antioxidant properties of carvedilol have generated interest in its use as a prophylaxis for postoperative AF.

These considerations led to the organization of COMPACT, a multi-center, randomized controlled trial of 650 patients designed to test the hypothesis that carvedilol is more effective than metoprolol, a conventional β1-selective antagonist, in suppressing new-onset AF following OPCAB surgery.

Study Timeline

• Study Start: 2005-01
• Study First Submitted: 2005-09-13
• Study First Submitted QC: 2005-09-13
• Study First Posted: 2005-09-20
• Status Verified: 2007-02
• Last Update Submitted: 2007-02-28
• Last Update Posted: 2007-03-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 650

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
The primary endpoint is the incidence of new-onset AF during the first seven days after surgery; AF is defined as an episode of atrial fibrillation or flutter lasting for >30 seconds as detected on the continuous cardiac monitor.

Secondary Outcome Measures

Name	Time	Method
the incidence of AF rhythm at hospital discharge
in-hospital mortality for any cause after surgery
in-hospital morbidity after surgery
resource use after surgery until hospital discharge.
the frequency of external or internal electrical cardioversion after surgery and before hospital discharge
the incidence, duration, and recurrence of new-onset AF after surgery and before hospital discharge
premature discontinuation of assigned drug administration

Trial Locations

Locations (1)

National Cardiovascular Center; 🇯🇵 Suita, Osaka, Japan