An overview of the clinical trials of agents (other than beta-blockers) that potentially limit myocardial infarct size.

In this article, data on mortality have been systematically reviewed from the randomized trials of intracoronary and intravenous (i.v.) thrombolytic therapy, hyaluronidase, i.v. nitrates, and calcium channel blockers in acute myocardial infarction (AMI). Such analyses confirm that i.v. streptokinase (SK) reduces short-term mortality by about 20%. Despite a higher incidence of reinfarction in the treated group, this early benefit is maintained long term. The excess reinfarction was observed whether or not SK was followed by anticoagulants or aspirin. The roles of pharmacologic interventions and percutaneous transluminal coronary angioplasty (PTCA) in preventing reinfarction and improving survival further are currently being evaluated. The pooled data from the existing trials of hyaluronidase and i.v. nitrates are consistent with a 20-30% reduction in mortality; ideally, these interventions should also be studied in future large randomized trials. Currently, there is no evidence either from individual studies or the aggregate of all the trials that calcium channel blockers reduce mortality. The collective experience from these trials conducted over the last two decades suggests that most interventions in AMI can at best have only moderate effects (10%, 20%, or at best 30%) on mortality. However, such modest effects produced by the widespread use of these agents could prevent several thousand premature deaths each years. Therefore, current and future trials that assess the effects of new or existing cardiovascular treatments on mortality should aim to randomize at least 10,000 average risk patients or a few thousand high risk patients.