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

This study has been completed.
Sponsor:
Information provided by:
Ministry of Health, Labour and Welfare, Japan
ClinicalTrials.gov Identifier:
NCT00198614
First received: September 13, 2005
Last updated: February 28, 2007
Last verified: February 2007
  Purpose

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.


Condition Intervention
Coronary Disease
Atrial Fibrillation
Drug: Carvedilol versus Metoprolol

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Comparison of the Effectiveness of Carvedilol Versus Metoprolol for Atrial Fibrillation Appearing After Off-Pump Coronary Bypass Surgery in the Carvedilol or Metoprolol Post-Revascularization Atrial Fibrillation Controlled Trial (COMPACT)

Resource links provided by NLM:


Further study details as provided by Ministry of Health, Labour and Welfare, Japan:

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

Estimated Enrollment: 650
Study Start Date: January 2005
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.

  Eligibility

Ages Eligible for Study:   20 Years to 89 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Adult male or female patients are required to meet the following criteria:

  1. Aged 20 to 89 years
  2. Underwent isolated off-pump coronary artery bypass graft surgery
  3. Written informed consent

Exclusion criteria:

Patients with the following conditions will be excluded from the study:

  1. Pre- and intraoperative use of mechanical circulatory support devices, except an intra-aortic balloon pump
  2. Concomitant operations, such as aneurysmectomy or carotid endarterectomy
  3. Surgical approaches other than a median full sternotomy
  4. Acute myocardial infarction ≦3 days before enrollment in the trial
  5. Contraindication against treatment with β blockers
  6. Presence of preoperative chronic AF or flutter
  7. History of paroxysmal AF
  8. Presence of antidysrhythmic medication other than β blockers, calcium channel blockers, or digitalis
  9. A resting heart rate of less than 50 beats/min in the absence of medical therapy known to slow the sinus rate
  10. Endocrine disorders, such as pheochromocytoma, active hyperthyroidism, and untreated hypothyroidism
  11. Pregnant women and females with childbearing potential unless utilizing adequate contraception
  12. Preoperative need for a temporary or permanent pacemaker
  13. Non-interpretable electrocardiogram for P wave assessment
  14. Undergoing treatment for asthma or other chronic obstructive pulmonary disease
  15. Second- or third-degree atrioventricular block
  16. Sick sinus syndrome
  17. Uncontrolled heart failure
  18. Unstable insulin-dependent diabetes mellitus
  19. Steroid therapy requirement
  20. History of autoimmune diseases
  21. Active infectious diseases, including myocarditis or pericarditis
  22. Any other serious disease that could potentially complicate the management and follow-up protocols
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00198614

Locations
Japan
National Cardiovascular Center
Suita, Osaka, Japan, 565-8565
Sponsors and Collaborators
Ministry of Health, Labour and Welfare, Japan
Investigators
Principal Investigator: Masakazu Kuro, M.D., Ph.D. Department of Anesthesiology, National Cardiovascular Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00198614     History of Changes
Other Study ID Numbers: 16C-9
Study First Received: September 13, 2005
Last Updated: February 28, 2007
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Ministry of Health, Labour and Welfare, Japan:
Adrenergic beta-Antagonists
Carvedilol
Metoprolol
Coronary Artery Bypass
Atrial Fibrillation

Additional relevant MeSH terms:
Atrial Fibrillation
Coronary Disease
Coronary Artery Disease
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Myocardial Ischemia
Vascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Adrenergic beta-Antagonists
Metoprolol
Metoprolol succinate
Carvedilol
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Antihypertensive Agents
Sympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic beta-1 Receptor Antagonists
Vasodilator Agents

ClinicalTrials.gov processed this record on July 24, 2014