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A Meta-analysis of Randomized Controlled Trials

David J. Bradley, MD, PhD; Elizabeth A. Bradley, MD; Kenneth L. Baughman, MD; Ronald D. Berger, MD, PhD; Hugh Calkins, MD; Steven N. Goodman, MD, PhD; David A. Kass, MD; Neil R. Powe, MD, MPH, MBA

JAMA. 2003;289:730-740.

Context  Progressive heart failure is the most common mechanism of death among patients with advanced heart failure. Cardiac resynchronization, a pacemaker-based therapy for heart failure, enhances cardiac performance and quality of life, but its effect on mortality is uncertain.

Objective  To determine whether cardiac resynchronization reduces mortality from progressive heart failure.

Data Sources  MEDLINE (1966-2002), EMBASE (1980-2002), the Cochrane Controlled Trials Register (Second Quarter, 2002), The National Institutes of Health ClinicalTrials.gov database, the US Food and Drug Administration Web site, and reports presented at scientific meetings (1994-2002). Search terms included pacemaker, pacing, heart failure, dual-site, multisite, biventricular, resynchronization, and left ventricular preexcitation.

Study Selection  Eligible studies were randomized controlled trials of cardiac resynchronization for the treatment of chronic symptomatic left ventricular dysfunction. Eligible studies reported death, hospitalization for heart failure, or ventricular arrhythmia as outcomes. Of the 6883 potentially relevant reports initially identified, 11 reports of 4 randomized trials with 1634 total patients were included in the meta-analysis.

Data Extraction  Trial reports were reviewed independently by 2 investigators in an unblinded standardized manner.

Data Synthesis  Follow-up in the included trials ranged from 3 to 6 months. Pooled data from the 4 selected studies showed that cardiac resynchronization reduced death from progressive heart failure by 51% relative to controls (odds ratio [OR], 0.49; 95% confidence interval [CI], 0.25-0.93). Progressive heart failure mortality was 1.7% for cardiac resynchronization patients and 3.5% for controls. Cardiac resynchronization also reduced heart failure hospitalization by 29% (OR, 0.71; 95% CI, 0.53-0.96) and showed a trend toward reducing all-cause mortality (OR, 0.77; 95% CI, 0.51-1.18). Cardiac resynchronization was not associated with a statistically significant effect on non–heart failure mortality (OR, 1.15; 95% CI, 0.65-2.02). Among patients with implantable cardioverter defibrillators, cardiac resynchronization had no clear impact on ventricular tachycardia or ventricular fibrillation (OR, 0.92; 95% CI, 0.67-1.27).

Conclusions  Cardiac resynchronization reduces mortality from progressive heart failure in patients with symptomatic left ventricular dysfunction. This finding suggests that cardiac resynchronization may have a substantial impact on the most common mechanism of death among patients with advanced heart failure. Cardiac resynchronization also reduces heart failure hospitalization and shows a trend toward reducing all-cause mortality.

Author Affiliations: Divisions of Cardiology (Drs D. Bradley, Baughman, Berger, Calkins, and Kass), General Internal Medicine (Dr Powe), Department of Medicine; Department of Ophthalmology (Dr E. Bradley); Department of Oncology (Dr Goodman), Johns Hopkins School of Medicine; Departments of Biostatistics (Dr Goodman), Epidemiology (Drs Goodman and Powe), and Health Policy and Management (Dr Powe), Johns Hopkins School of Public Health; Welch Center for Prevention, Epidemiology, and Clinical Research (Dr Powe), Johns Hopkins School of Medicine and School of Public Health, Baltimore, Md; Department of Ophthalmology, Mayo Clinic and Mayo Foundation, Rochester, Minn (Dr E. Bradley). Dr Baughman is currently with the Division of Cardiology at Brigham and Women's Hospital, Boston, Mass.

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RELATED LETTERS

Cardiac Resynchronization for Progressive Heart Failure
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JAMA. 2003;290(1):37-38.
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