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.
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 β-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 (β-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
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
β-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 β-blockers than with calcium antagonists.
β-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 β-blockers and calcium
antagonists were most striking for nifedipine (OR for adverse events
with β-blockers vs nifedipine, 0.60; 95% CI, 0.47-0.77). Too few
trials compared nitrates with calcium antagonists or β-blockers to
draw firm conclusions about relative efficacy.
Conclusions β-Blockers provide similar clinical outcomes and are
associated with fewer adverse events than calcium antagonists in
randomized trials of patients who have stable angina.
Heidenreich PA, McDonald KM, Hastie T, et al. Meta-analysis of Trials Comparing β-Blockers, Calcium Antagonists, and Nitrates for Stable Angina. JAMA. 1999;281(20):1927–1936. doi:https://doi.org/10.1001/jama.281.20.1927
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