Design of a placebo-controlled clinical trial of long-acting diltiazem and aspirin versus aspirin alone in patients receiving thrombolysis with a first acute myocardial infarction. Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis (diltiazem) (INTERCEPT) Research Group.
Several pharmacologic forms of adjunctive therapy, designed to enhance the efficacy of thrombolysis following acute myocardial infarction (AMI), are being explored. However, few studies have assessed the use of standard secondary prevention therapies (beta-blockers, angiotensin-converting enzyme inhibitors, magnesium, calcium antagonists, etc.) for antecedent thrombolysis. Although calcium antagonists have not been shown to alter post-AMI mortality, diltiazem has been shown to reduce recurrent nonfatal infarction and myocardial ischemia following non-Q-wave AMI. Because both non-Q-wave AMI and AMI treated with thrombolytic therapy result in early reperfusion and clinical manifestations of "incomplete infarction" (i.e., aborted transmural infarction), we hypothesize that prophylactic administration of diltiazem to AMI patients who receive thrombolysis before other therapies might decrease ischemic complications. We have initiated a multicenter, randomized, placebo-controlled, double-blind, parallel-group comparison of long-acting diltiazem 300 mg/day and aspirin 160 mg/day versus aspirin 160 mg/day alone in up to 920 patients with an uncomplicated first AMI (no heart failure or left ventricular dysfunction) within 36 to 96 hours of receiving thrombolysis. Active enrollment is under way at 46 centers in the United Kingdom, Belgium, The Netherlands, and Denmark. This trial (known as the Incomplete INfarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis [diltiazem], or INTERCEPT) represents the first long-term, large-scale, prospective study of a calcium antagonist administered post-thrombolysis as adjunctive therapy to AMI patients in which the primary trial objective is to assess the effect of blinded therapy on the 6-month cumulative occurrence of a combined clinical end point (cardiac death, recurrent nonfatal AMI, and medically refractory ischemia).