Anti-ischaemic therapy during the follow-up phase of acute coronary syndromes. Is there a role for calcium channel blockers?

Abstract

Various pharmacological strategies are currently being sought to enhance the efficacy of thrombolysis after an acute myocardial infarction (AMI). Apart from the use of new thrombolytic agents, novel anticoagulants and antiplatelet drugs, attention has recently been focused on agents such as the calcium channel blockers (calcium antagonists) traditionally used (prior to the thrombolytic era) for secondary prevention after an AMI. In this context, although calcium channel blockers have not been definitively proven to have any benefit with regard to all-cause mortality or subsequent infarctions, diltiazem has been shown to reduce cardiac mortality, recurrent nonfatal infarction and myocardial ischaemia after non-Q-wave AMI. These benefits have been linked to the drug's effect of lowering heart rate. Since both non-Q-wave AMI and the AMI treated with thrombolytic therapy result in early reperfusion and clinical manifestations of 'incomplete infarction', and are characterised by a similar high incidence of ischaemic complications, it is plausible to hypothesise that prophylactic calcium channel blocker administration to AMI patients post-thrombolysis might decrease the cumulative occurrence of reinfarction and refractory ischaemia during long term follow-up. With this in mind, the Incomplete INfarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis with Tildiem was initiated in September 1994. This represents the first prospective study to investigate the efficacy of a calcium channel blocker (long-acting diltiazem 300 mg/day) administered as adjunctive therapy with aspirin 160 mg/day in up to 920 patients with an uncomplicated first AMI receiving early thrombolytic therapy. The primary trial objective is to assess the efficacy of blinded therapy on the 6-month cumulative occurrence of a combined clinical end-point (cardiac death, recurrent non-fatal infarction, medically refractory ischaemia)-an end-point identical to that utilised in the assessment of diltiazem in non-Q-wave AMI.