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Meta-analysis of Trials Comparing -Blockers, Calcium Antagonists, and Nitrates for Stable Angina

Paul A. Heidenreich, MD, MS; Kathryn M. McDonald, MM; Trevor Hastie, PhD; Bahaa Fadel, MD; Vivian Hagan; Byron K. Lee, MD; Mark A. Hlatky, MD

JAMA. 1999;281:1927-1936.

Context  Which drug is most effective as a first-line treatment for stable angina is not known.

Objective  To compare the relative efficacy and tolerability of treatment with -blockers, calcium antagonists, and long-acting nitrates for patients who have stable angina.

Data Sources  We identified English-language studies published between 1966 and 1997 by searching the MEDLINE and EMBASE databases and reviewing the bibliographies of identified articles to locate additional relevant studies.

Study Selection  Randomized or crossover studies comparing antianginal drugs from 2 or 3 different classes (-blockers, calcium antagonists, and long-acting nitrates) lasting at least 1 week were reviewed. Studies were selected if they reported at least 1 of the following outcomes: cardiac death, myocardial infarction, study withdrawal due to adverse events, angina frequency, nitroglycerin use, or exercise duration. Ninety (63%) of 143 identified studies met the inclusion criteria.

Data Extraction  Two independent reviewers extracted data from selected articles, settling any differences by consensus. Outcome data were extracted a third time by 1 of the investigators. We combined results using odds ratios (ORs) for discrete data and mean differences for continuous data. Studies of calcium antagonists were grouped by duration and type of drug (nifedipine vs nonnifedipine).

Data Synthesis  Rates of cardiac death and myocardial infarction were not significantly different for treatment with -blockers vs calcium antagonists (OR, 0.97; 95% confidence interval [CI], 0.67-1.38; P=.79). There were 0.31 (95% CI, 0.00-0.62; P=.05) fewer episodes of angina per week with -blockers than with calcium antagonists. -Blockers were discontinued because of adverse events less often than were calcium antagonists (OR, 0.72; 95% CI, 0.60-0.86; P<.001). The differences between -blockers and calcium antagonists were most striking for nifedipine (OR for adverse events with -blockers vs nifedipine, 0.60; 95% CI, 0.47-0.77). Too few trials compared nitrates with calcium antagonists or -blockers to draw firm conclusions about relative efficacy.

Conclusions  -Blockers provide similar clinical outcomes and are associated with fewer adverse events than calcium antagonists in randomized trials of patients who have stable angina.

Author Affiliations: Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif (Dr Heidenreich); and the Departments of Health Research and Policy (Drs Heidenreich, Hastie, and Hlatky and Mss McDonald and Hagan), Medicine (Drs Heidenreich, Fadel, Lee, and Hlatky and Ms McDonald), and Statistics (Dr Hastie), Stanford University, Stanford, Calif.

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