Thrombolysis and its sequelae. Calcium antagonists as potential adjunctive therapy.

Randomized, placebo-controlled trials have documented that both streptokinase and rt-PA given early are associated with limitation of infarct size, improved ventricular function, and reduced mortality. Other concerns, however, documented experimentally include myocardial hemorrhage, the "no-reflow" phenomenon, myocardial "stunning," reperfusion-induced injury, and clinically, rethrombosis that occurs at a rate of 20% and reinfarction at 8-10%. Thus, even with the ideal thrombolytic agent, adjunctive therapy to prevent rethrombosis will remain a requisite to obtaining long-term benefit. Calcium blockers in association with reperfusion have been shown experimentally to be protective, resulting in limitation of infarct size and improved ventricular function. There is no data on the role of calcium blockers in conjunction with thrombolysis in patients. Results are available from two randomized trials with the calcium blocker, diltiazem, in patients with non-Q wave infarction. In the short-term trial involving 576 patients with non-Q wave infarction, the incidence of early reinfarction was reduced by 50%, and in the long-term study (non-Q wave infarction, n = 634), reinfarction and death were reduced by 40% after 1 year and by 34% after 4.5 years. Non-Q wave infarction is believed to undergo early spontaneous reperfusion based on the following: small infarct size, contracture necrosis at postmortem, early peaking of plasma CK, coronary patency on angiography, residual ischemia, and a high incidence of reinfarction. Thus, thrombolysis occurring spontaneously or induced therapeutically is associated with a high incidence of reinfarction. The implications of these clinical studies together with the experimental data suggests that the hypothesis of a calcium blocker being important adjunctive therapy following thrombolysis is worthy of clinical evaluation.