Medical management of unstable angina. What have we learned from the randomized trials?

Because of the absence of a generally accepted definition of unstable angina, the clinical context of drug trials for this condition has varied from trial to trial. Early- versus late-entry trials must be distinguished, and the possibility of a modification of effect caused by the nature of drug therapy already given when the patient became unstable or by concomitant treatment in addition to experimental treatment must be taken into account. These factors cannot be overlooked when the results from a limited number of reported trials are pooled together. The largest early-entry trial with a beta-blocker and a calcium antagonist was the Holland Interuniversity Nifedipine/metoprolol Trial (HINT), which enrolled patients with suspected unstable angina diagnosed at coronary care unit admission. HINT results showed that unstable angina cannot be reliably differentiated from evolving myocardial infarction (MI) in this particular context and that there are few early MIs that could have been prevented. In patients who were not already taking a beta-blocker, metoprolol reduced the incidence of acute MI or recurrent ischemia, and there was no benefit of nifedipine. On the other hand, the addition of nifedipine was effective in patients whose conditions became unstable despite maintenance treatment with a beta-blocker. Thus, previous beta-blockade modified the effect of the calcium antagonist studied. Based on evidence from HINT and other trials, it is concluded that beta-blockers should be used as the first-line treatment in patients with unstable angina and that a calcium antagonist should be added when patients remain unstable despite beta-blockade.(ABSTRACT TRUNCATED AT 250 WORDS)