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).