SAFETY OF NIFEDIPINE IN PATIENTS WITH HYPERTENSION - A METAANALYSIS

Our objective was to compare cardiovascular event rates in patients wi th mild or moderate hypertension who received nifedipine with active d rug controls. We performed a MEDLARS search using the MeSH heading ''h ypertension'' and the text word ''nifedipine'' to identify all article s that were published between 1966 and August 1995 in English, French, German, Italian, and Spanish languages and that involved human subjec ts. The computerized search was supplemented by a manual search of art icle bibliographies. Review of 1880 citations revealed 98 randomized c ontrolled clinical trials that met protocol criteria. Articles were ex tracted independently by two doctors who were blinded for author, inst itution, and treatment regimen, using a structured, pretested extracti on form. Differences of opinion were resolved by consensus. Fourteen e vents occurred in 5198 exposures (0.27%) to nifedipine and 24 events i n 5402 exposures (0.44%) to other active drug controls. Unadjusted odd s ratios for nifedipine versus controls were 0.49 (95% confidence inte rval [CI], 0.22-1.09) for definitive events (death, nonfatal myocardia l infarction or stroke, revascularization procedure) and 0.61 (95% CI, 0.31-1.17) for all events (definitive plus increased angina). The odd s ratio for nifedipine monotherapy (sustained- or extended-release in 91% of exposures) was nonsignificantly higher for definitive and all e vents (odds ratio, 1.40; 95% CI, 0.49-4.03 and odds ratio, 1.39; 95% C I, 0.59-3.32, respectively). The odds ratio for nifedipine in combinat ion with another drug was significantly lower for definitive and all e vents (odds ratio, 0.09; 95% CI, 0.01-0.66 and odds ratio, 0.15, 95% C I, 0.03-0.65, respectively). Differences in odds ratio for nifedipine monotherapy and combined therapy were statistically significant (P=.02 for definitive events and P=.001 for all events). Results support the safety of sustained- and extended-release nifedipine in the treatment of mild or moderate hypertension when it is used in combination with other drugs.