Safety of nifedipine in angina pectoris - A meta-analysis

Our objective was to compare cardiovascular event rates in patients with st able angina receiving nifedipine as monotherapy or combination therapy and in active drug controls. A MEDLARS search of published articles from 1966 t o 1995 in English, French, German, Italian, or Spanish, supplemented by a m anual search of bibliographies, identified 60 randomized controlled trials that met protocol criteria. Blinded articles were extracted by 2 physicians . The pooled risks of death, withdrawal, and cardiovascular event were comp uted and expressed as odds ratios (ORs) for all nifedipine formulations and relative to same study control drug regimens. Thirty cardiovascular events were reported in 2635 nifedipine exposures (1.14%) and 19 events in 2655 o ther active drug exposures (0.72%). Unadjusted ORs for nifedipine versus co ntrols were 1.40 (95% CI, 0.56 to 3.49) for major events (death, nonfatal m yocardial infarction, stroke, revascularization procedure), 1.75 (95% CI, 0 .83 to 3.67) for increased angina, and 1.61 (95% CI, 0.91 to 2.87) for all events (major events plus increased angina). Episodes of increased angina w ere more frequent on immediate-release nifedipine (OR, 4.19 [95% CI, 1.41 t o 12.49]) and on nifedipine monotherapy (OR, 2.61 [95% CI, 1.30 to 5.26]). The OR for immediate-release nifedipine was significantly higher than that for sustained-release/extended-release nifedipine (P=0.001), and the OR for nifedipine monotherapy was higher than that for nifedipine combination the rapy (P=0.03). Increased risks of cardiovascular events in patients with st able angina on nifedipine were due primarily to more episodes of increased angina, confined to the immediate-release formulation and to nifedipine mon otherapy.