Nifedipine and metoprolol in unstable angina: findings from the Holland Interuniversity Nifedipine/Metoprolol Trial (HINT)

Abstract

We conducted a multicenter, double-blind, placebo-controlled, randomized trial of nifedipine, metoprolol, and their combination in 338 patients whose hospital admission diagnosis was unstable angina and who were not pretreated with a beta-blocker, and of nifedipine in 177 patients who were treated with a beta-blocker. The main outcome event was the recurrence of ischemia or progression to myocardial infarction within 48 h. Trial medication effects are expressed as ratios of event rates relative to placebo, e.g., the ratio for nifedipine is the event rate under nifedipine divided by that under placebo. In addition, 95% confidence intervals are given. In patients not pretreated with a beta-blocker, the event rate ratio for nifedipine was 1.15 (0.83, 1.64), for metoprolol 0.76 (0.49, 1.16), and for the combination 0.80 (0.53, 1.19). In patients already on a beta-blocker, the addition of nifedipine was favorable; i.e., the rate ratio was 0.68 (0.47, 0.97). Equal numbers of patients developed myocardial infarction and reversible ischemia. Most infarctions occurred early, within 6 h of randomization. In patients not already on a beta-blocker, the nifedipine rate ratio for infarction was 1.51 (0.87, 2.74). These results suggest that, in patients not on previous beta-blockade, metoprolol has a beneficial short-term effect on unstable angina, a fixed combination with nifedipine provides no further gain, and nifedipine may be ineffective or counterproductive. On the other hand, the addition of nifedipine to existing beta-blockade when the patient becomes unstable seems beneficial.