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CLINICAL STUDY

Efficacy of angiotensin-converting enzyme inhibitors and beta-blockers in the management of left ventricular systolic dysfunction according to race, gender, and diabetic status

A meta-analysis of major clinical trials

Paul G. Shekelle, MD, PhD^*,*, Michael W. Rich, MD, Sally C. Morton, PhD^*, Col. Sid W. Atkinson, MD^||, Wenli Tu, MS^*, Margaret Maglione, MPP^*, Shannon Rhodes, MFA^*, Michael Barrett, MD^¶, Gregg C. Fonarow, MD^#**, Barry Greenberg, MD, Paul A. Heidenreich, MD, MS, Tom Knabel, MD^||||, Marvin A. Konstam, MD^¶¶, Anthony Steimle, MD^## and Lynne Warner Stevenson, MD^***

^* Southern California Evidence-Based Practice Center, RAND Health, Santa Monica, California, USA
Division of General Internal Medicine, Greater Los Angeles VA Medical Center, Los Angeles, California, USA
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
RAND Arroyo Center, Santa Monica, California, USA
^|| Southeast Regional Medical Command, U.S. Army Medical Department, Athens, Georgia, USA
^¶ Department of Medicine, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA
^# Ahmanson-UCLA Cardiomyopathy Center, Los Angeles, California, USA
^** Division of Cardiology, University of California at Los Angeles, Los Angeles, California, USA
Heart Failure/Cardiac Transplantation Program, University of California, San Diego, California, USA
Department of Medicine, Stanford University, Stanford, California, USA
VA Palo Alto Healthcare System, Stanford, California, USA
^|||| Ingenix, Eden Prairie, Minnesota, USA
^¶¶ Department of Medicine, Division of Cardiology, Tufts-New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts, USA
^## Heart Failure Program, Kaiser Permanente Northern California, Santa Clara, California, USA
^*** Cardiomyopathy and Heart Failure Program, Brigham and Women’s Hospital, Boston, Massachusetts, USA
Harvard Medical School, Boston, Massachusetts, USA

Manuscript received September 20, 2002; revised manuscript received January 22, 2003, accepted January 30, 2003.

^* Reprint requests and correspondence: Dr. Paul G. Shekelle, RAND, 1700 Main Street, P. O. Box 2138, Santa Monica, California 90407-2138, USA.
shekelle{at}rand.org

OBJECTIVES: This study sought to assess the effect of angiotensin-converting enzyme (ACE) inhibitors and beta-blockers on all-cause mortality in patients with left ventricular (LV) systolic dysfunction according to gender, race, and the presence of diabetes.

BACKGROUND: Major randomized clinical trials have established that ACE inhibitors and beta-blockers have life-saving benefits in patients with LV systolic dysfunction. Most patients enrolled in these trials were Caucasian men. Whether an equal effect is achieved in women, non-Caucasians, and patients with major comorbidities has not been established.

METHODS: The authors performed a meta-analysis of published and individual patient data from the 12 largest randomized clinical trials of ACE inhibitors and beta-blockers to produce random effects estimates of mortality for subgroups.

RESULTS: Data support beneficial reductions in all-cause mortality for the use of beta-blockers in men and women, the use of ACE inhibitors and some beta-blockers in black and white patients, and the use of ACE inhibitors and beta-blockers in patients with or without diabetes. Women with symptomatic LV systolic dysfunction probably benefit from ACE inhibitors, but women with asymptomatic LV systolic dysfunction may not have reduced mortality when treated with ACE inhibitors (pooled relative risk = 0.96; 95% confidence interval: 0.75 to 1.22). The pooled estimate of three beta-blocker studies supports a beneficial effect in black patients with heart failure, but one study assessing bucindolol reported a nonsignificant increase in mortality.

CONCLUSIONS: Angiotensin-converting enzyme inhibitors and beta-blockers provide life-saving benefits in most of the subpopulations assessed. Women with asymptomatic LV systolic dysfunction may not achieve a mortality benefit when treated with ACE inhibitors.

Abbreviations and Acronyms   ACE = angiotensin-converting enzyme   AIRE = Acute Infarction Ramipril Efficacy   BEST = Beta-blocker Evaluation of Survival Trial   CI = confidence interval   CIBIS = Cardiac Insufficiency Bisoprolol Study   CONSENSUS = Cooperative North Scandinavian Enalapril Survival Study   COPERNICUS = Carvedilol Prospective Randomized Cumulative Survival Study   HF = heart failure   HR = hazard ratio   LV = left ventricular   MERIT-HF = Metoprolol Extended-release Randomized Intervention Trial in Heart Failure   RR = relative risk   RRR = ratio of relative risks   SAVE = Survival And Ventricular Enlargement   SMILE = Survival of Myocardial Infarction Long-term Evaluation   SOLVD = Studies Of Left Ventricular Dysfunction   TRACE = Trandolapril Cardiac Evaluation

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