THIS EVIDENCE REPORT IS OUTDATED AND IS NO LONGER VIEWED AS GUIDANCE FOR CURRENT MEDICAL PRACTICE. IT IS MAINTAINED FOR ARCHIVAL PURPOSES ONLY.

Evidence Report/Technology Assessment

Number 10

Prepared for:
Agency for Healthcare Research and Quality

U.S. Department of Health and Human Services
2101 East Jefferson Street
Rockville, MD 20852

Contract No. 290-97-0013

Prepared by:
University of California, San Francisco-Stanford
Paul A. Heidenreich, M.D., M.Sc.
Principal Investigator

Kathryn M. McDonald, M.M.
Trevor Hastie, Ph.D.
Bahaa Fadel, M.D.
Vivian Hagan
Byron K. Lee, M.D.
Mark A. Hlatky, M.D.

AHRQ Publication No. 00-E003

November 1999

The Agency for Healthcare Research and Quality (AHRQ, formerly the Agency for Health Care Policy and Research, AHCPR), through its Evidence-based Practice Centers (EPCs), sponsors the development of evidence reports and technology assessments to assist public- and private-sector organizations in their efforts to improve the quality of health care in the United States. The reports and assessments provide organizations with comprehensive, science-based information on common, costly medical conditions and new health care technologies. The EPCs systematically review the relevant scientific literature on topics assigned to them by AHRQ and conduct additional analyses when appropriate prior to developing their reports and assessments.

To bring the broadest range of experts into the development of evidence reports and health technology assessments, AHRQ encourages the EPCs to form partnerships and enter into collaborations with other medical and research organizations. The EPCs work with these partner organizations to ensure that the evidence reports and technology assessments they produce will become building blocks for health care quality improvement projects throughout the Nation. The reports undergo peer review prior to their release.

AHRQ expects that the EPC evidence reports and technology assessments will inform individual health plans, providers, and purchasers as well as the health care system as a whole by providing important information to help improve health care quality.

We welcome written comments on this evidence report. They may be sent to: Director, Center for Practice and Technology Assessment, Agency for Healthcare Research and Quality, 6010 Executive Blvd., Suite 300, Rockville, MD 20852.

Douglas B. Kamerow, M.D.	John M. Eisenberg, M.D.
Director, Center for Practice and Technology Assessment	Director, Agency for Healthcare Research and Quality

The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services of a particular drug, device, test, treatment, or other clinical service.

This report was developed with support from the Agency for Health Care Policy and Research, now the Agency for Healthcare Research and Quality. Dr. Heidenreich is supported by a career development award from the Veterans Affairs Health Services Research and Development Service. The authors thank Lyn Dupré, Mary Grady, and the peer reviewers for comments on the manuscript, and the members of the University of California, San Francisco (UCSF)-Stanford EPC Governing Council for their suggestions. The authors also thank Francis Chesley, M.D., and the members and support staff of the Stable Angina Guidelines Committee (American College of Cardiology, American Heart Association, American College of Physicians) for guidance throughout the project; Dr. Drummond Rennie and Dr. Lisa Bero for developing a peer review process for evidence reports; and Dr. Patricia Huston for developing a coherent and constructive synthesis of peer review commentaries.

Stable angina is a major health problem that affects over 7 million adults in the United States, with an estimated 350,000 new cases annually. The American College of Cardiology, American Heart Association, and American College of Physicians established a committee to develop guidelines for the diagnosis and treatment of stable angina. This committee of experts in cardiology and internal medicine and the investigators from the University of California, San Francisco (UCSF)-Stanford Evidence-based Practice Center (EPC) prioritized two topics for a thorough systematic review of the literature. The first topic concerned the relative efficacy and tolerability of treatment with beta-blockers, calcium antagonists, and long-acting nitrates for patients who have stable angina. The second topic dealt with the efficacy of alternative therapies in patients who have stable angina.

The authors identified published studies from 1966 through 1997 by searching the MEDLINE and EMBASE databases and by reviewing manually the bibliographies of identified articles.

For the review of traditional therapies, studies that compared two agents from different anti-anginal drug classes (beta-blockers, calcium antagonists, and nitrates) and that were at least 1 week in duration were reviewed. Studies were selected if they reported one of the following outcomes: cardiac death, myocardial infarction, angina frequency, nitroglycerin use, exercise duration, or adverse events leading to withdrawal. For the review of alternative therapies, the authors included all randomized trials of alternative therapies compared with placebo, nitrates, calcium antagonists, or beta-blockers in patients who had stable angina.

For the review of traditional therapies, 91 studies met the inclusion criteria. Each study was abstracted by two independent reviewers. The data were pooled using odds ratios for discrete data and mean differences for continuous data. Studies of calcium antagonists were grouped by duration of action (short- vs. long-acting) and type of drug (nifedipine vs. nonnifedipine).

Rates of cardiac death or myocardial infarction were similar (odds ratio 0.97 [0.67,1.38]), but events were few; the median trial duration was 4 weeks. Beta-blockers provided greater angina relief than calcium antagonists did: mean difference in episodes per week was 0.31 (95 percent confidence interval: 0.00, 0.62). Beta-blockers were discontinued after adverse events less often than calcium antagonists were (odds ratio 0.72 [95 percent confidence interval: 0.60, 0.86]). Trials comparing nifedipine with beta-blockers showed a significantly greater benefit for angina relief for beta-blockers and a decrease in adverse events leading to study withdrawal. Commonly reported side effects were similar or greater in patients taking calcium antagonists compared with patients taking beta-blockers. Randomized trials of alternative therapies for patients who had stable angina were too small and too few to allow conclusions to be drawn.

In trials of patients who had stable angina, beta-blockers provided equivalent or greater angina relief than calcium antagonists and were associated with fewer adverse events. No differences were documented in mortality or myocardial infarction, but trial duration was too short to define clinically important effects on these endpoints. There were too few studies of nitrates and alternative therapies to draw conclusions.

This document is in the public domain and may be used and reprinted without permission.

Heidenreich PA, McDonald KM, Hastie T, et al. An evaluation of beta-blockers, calcium antagonists, nitrates, and alternative therapies for stable angina. (Evidence Report/Technology Assessment No. 10 [Contract 290-97-0013] to the University of California San Francisco-Stanford Evidence-based Practice Center). AHRQ Publication No. 00-E003. Rockville, MD: Agency for Healthcare Research and Quality. November 1999.