Current issues of ACP Journal Club are published in Annals of Internal Medicine


Review: β-blockers have outcomes similar to calcium antagonists but cause fewer adverse events in stable angina

ACP J Club. 1999 Nov-Dec;131:62. doi:10.7326/ACPJC-1999-131-3-062

Source Citation

Heidenreich PA, McDonald KM, Hastie T, et al. Meta-analysis of trials comparing β-blockers, calcium antagonists, and nitrates for stable angina. JAMA. 1999 May 26;281;1927-36.



What is the relative effectiveness and safety of β-blockers, calcium antagonists, and long-acting nitrates in patients with stable angina?

Data sources

Studies were identified by searching MEDLINE (1966 to 1997) and EMBASE/Excerpta Medica (1974 to 1997) using the terms angina pectoris, angina, randomized controlled trial, controlled clinical trial, random, and double-blind and by searching bibliographies of relevant papers.

Study selection

Randomized controlled or crossover trials were selected if they directly compared antianginal drugs from 2 or 3 different classes; included patients with stable angina; lasted ≥ 1 week; and reported cardiac death or myocardial infarction (MI), withdrawal because of adverse events, angina frequency, nitroglycerin use, or exercise duration.

Data extraction

Study characteristics, treatment comparisons, cardiac death or MI, angina episodes/wk, nitroglycerin use/wk, total exercise time, time to 1-mm ST depression, and withdrawal because of adverse events.

Main results

143 studies were identified, and 90 trials met the selection criteria. 72 studies (mean duration 8 wk, participants' mean age 57 y) compared β-blockers with calcium antagonists, 12 studies (mean duration 3 wk, participants' mean age 62 y) compared long-acting nitrates with calcium antagonists, and 6 studies (mean duration 5 wk, participants' mean age 57 y) compared long-acting nitrates with β-blockers. Meta-analysis showed that β-blockers and calcium antagonists did not differ for the rate of cardiac death or MI (P = 0.85, 61 studies) (Table), nitroglycerin use/wk (weighted mean difference [WMD] -0.14, CI -0.42 to 0.32, P = 0.32, 25 studies), or time to 1-mm ST depression (WMD 0.06, CI -0.06 to 0.18, P = 0.33, 20 studies); however, β-blockers were associated with decreased angina episodes/wk (WMD -0.31, CI -0.62 to 0, P = 0.05, 32 studies), total exercise time (WMD -0.10, CI -0.20 to 0, P = 0.05, 32 studies), and withdrawals because of adverse events { P = 0.003, 23 studies}* (Table). Long-acting nitrates did not differ from calcium antagonists or β-blockers for any of the outcomes measured.


In patients with stable angina, β-blockers and calcium antagonists have similar clinical outcomes. β-blockers result in fewer withdrawals because of adverse events.

Source of funding: Agency for Health Care Policy and Research.

For correspondence: Dr. P.A. Heidenreich, 111C Cardiology, Palo Alto VA Medical Center, 3801 Miranda Avenue, Palo Alto, CA 94304, USA. FAX 650-852-3473.

*Data supplied by author.

Table. β-blockers vs calcium antagonists for patients with stable angina at an approximate mean follow-up of 8 weeks†

Outcomes Weighted event rates RRR (95% CI) NNT (CI)
β-blockers Calcium antagonists
Cardiac death or MI 1.8% 1.9% 4.5% (-37 to 33) Not significant
Withdrawal for adverse events 10.4% 14.2% 26% (13 to 36) 42 (25 to 123)

†Abbreviations defined in Glossary; all numbers supplied by author.


The meta-analysis by Heidenreich and colleagues compares 3 main classes of pharmaceutical agents for angina: β-blockers, calcium antagonists, and oral nitrates. Because most of the studies reviewed had short-term follow-up, inferences about long-term end points, such as mortality and MI, cannot be made.

Because they reduce death and MI in patients with hypertension or those who have had MI, β-blockers should also remain the first-line treatment for patients with stable angina (1). This meta-analysis shows that β-blockers used in the short term are the most tolerable and are at least as effective as other antianginal agents. The results dispel a myth that calcium antagonists are better tolerated than β-blockers. As in other groups of patients, short-acting dihydropyridines seem to be the least tolerated, and even long-acting dihydropyridines were neither better tolerated nor more effective than β-blockers.

Although the study compared trials of single agents, it seems that calcium antagonists should be used as second-line therapy in patients who cannot tolerate β-blockers (e.g., because of lung disease) or who remain symptomatic despite adequate doses of β-blockers. Long-acting oral nitrates can also be second-line therapy for patients who are symptomatic despite β-blocker therapy. Calcium antagonists seemed to be better tolerated and more effective than nitrates as single agents, but the sample sizes were too small to draw any definite conclusions about the relative safety and efficacy of these 2 second-line drugs.

Steven Borzak, MD
Henry Ford Heart and Vascular InstituteDetroit, Michigan, USA


1. Freemantle N, Cleland J, Young P, Mason J, Harrison J. Beta blockade after myocardial infarction: systematic review and meta regression analysis. BMJ. 1999;318:1730-7.