Meta-analysis: β-blockers improve function in dilated cardiomyopathy
ACP J Club. 1997 Mar-Apr;126:34. doi:10.7326/ACPJC-1997-126-2-034
Zarembski DG, Nolan PE Jr, Slack MK, Lui CY. Meta-analysis of the use of low-dose beta-adrenergic blocking therapy in idiopathic or ischemic dilated cardiomyopathy. Am J Cardiol. 1996 Jun 1;77:1247-50.
To determine the effectiveness of β-blockers for improving quality of life and hemodynamic indexes in patients with idiopathic or ischemic cardiomyopathy.
Studies were identified by searching Current Contents: Clinical Practice and MEDLINE (1960 to November 1995).
Studies were selected if they were randomized, placebo-controlled trials that evaluated the use of β-adrenergic blocking agents for ≥ 3 months in patients with left ventricular ejection fraction (LVEF) < 40%.
Data were extracted on patient age and sex, number of patients participating, type of cardiomyopathy and β-blocking agent, daily dose, duration of the trial, and change in New York Heart Association (NYHA) functional class and LVEF.
11 trials involving 623 patients (335 in the β-blocker group and 288 in the placebo group) met the selection criteria. 4 β-adrenergic blocking agents were studied: metorprolol (n = 290), bucindolol (n = 160), carvedilol (n = 149), and nebivolol (n = 24). The pooled sample population was 73% men with a mean age of 50 years. Effect sizes were calculated by pooling data across trials. 7 of the 11 trials had complete data on NYHA functional class. In the β-blocker and placebo groups, the mean NYHA functional classes were similar at baseline (2.64 and 2.67, respectively) and improved at the conclusion of the trials (to 2.03 and 2.51, respectively; P < 0.001 in favor of the β-blocker groups). Complete data on LVEF was available in 10 trials. In the β-blocker and placebo groups, the mean baseline LVEFs were similar (21.3% and 21.2%, respectively) and improved at the conclusion of the trials (to 29.7% and 23.4%, respectively; P < 0.04 in favor of the β-blocker groups).
β-adrenergic blocking agents improve New York Heart Association functional class and left ventricular ejection fraction in patients with idiopathic or ischemic cardiomyopathy.
Source of funding: American Society of Hospital Pharmacists Research and Education Foundation.
For article reprint: Dr. P.E. Nolan, Department of Pharmacy Practice 2nd Science, College of Pharmacy, The University of Arizona, 1703 East Mabel, Tucson, AZ 85721, USA. FAX 520-626-7355.
The rationale for using β-blockers in the treatment of heart failure is that sympathetic activation plays a key role in the pathogenesis and progression of this condition. The results of this meta-analysis by Zarembski and colleagues confirm the effect of β-blockers for improving functional class and LVEF in patients with idiopathic or ischemic dilated cardiomyopathy. Nonetheless, important questions that are relevant to clinical practice remain unanswered.
First, the end points addressed in this meta-analysis are intermediate outcomes. What is the effect of β-blockers on survival? Completed long-term trials of metoprolol and bisoprolol suggest that β-blockers may have a favorable effect on the course and prognosis of heart failure in some patients (1), but the reductions in morbidity and mortality did not reach statistical significance in these studies. A recent large-scale randomized clinical trial of more than 1000 patients treated with carvedilol showed a 65% relative risk reduction in mortality (2). Is the result of this single trial sufficient to justify a recommendation?
Second, the results of this meta-analysis do not indicate whether patients with idiopathic or ischemic cardiomyopathy receive the most benefit from the treatment. Although the authors speculate that the response to β-blockers is less in patients with ischemic cardiomyopathy, no clear difference was shown in the meta-analysis.
Third, the results of this meta-analysis do not indicate what type of β-blockers (those with vasodilator properties or with only β-adrenergic blockage) are the most beneficial. Preliminary evidence shows that drugs that block both α1- and β2-adrenergic receptors prolong survival in heart failure (2).
Questions about the role of β-blockers as therapy for heart failure remain unresolved but may be answered by large clinical trials that are now under way.
Carlos Brotons, MD, MPH
Vall d'Hebron University HospitalBarcelona, Spain
Carlos Brotons, MD, MPH
Vall d'Hebron University Hospital