Related Experiment Videos
Thrombolysis and its sequelae. Calcium antagonists as potential adjunctive therapy
1Baylor College of Medicine, Methodist Hospital, Houston, Texas 77030.
Insights
Thrombolytic therapy for heart attacks improves outcomes but risks rethrombosis. Calcium blockers, like diltiazem, show promise as adjunctive therapy to prevent reinfarction and improve long-term benefits.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Thrombolytic therapy (streptokinase, rt-PA) limits infarct size and improves outcomes but has risks like rethrombosis.
- Experimental data suggests calcium blockers protect the heart during reperfusion.
- Clinical data on calcium blockers combined with thrombolysis is lacking.
Purpose of the Study:
- To evaluate the potential role of calcium blockers as adjunctive therapy following thrombolysis.
- To assess the impact of calcium blockers on reinfarction rates and long-term outcomes in patients with non-Q wave infarction.
Main Methods:
- Review of randomized, placebo-controlled trials on thrombolytic agents.
- Analysis of two randomized trials using diltiazem in patients with non-Q wave infarction.
- Consideration of experimental data on calcium blockers and reperfusion injury.
Main Results:
- Two trials involving diltiazem in non-Q wave infarction showed reduced early reinfarction by 50%.
- Long-term follow-up (1-4.5 years) demonstrated a 34-40% reduction in reinfarction and death.
- Non-Q wave infarction is associated with spontaneous reperfusion and a high reinfarction rate.
Conclusions:
- Thrombolysis, spontaneous or therapeutic, is linked to a high reinfarction incidence.
- Calcium blockers may be a crucial adjunctive therapy to prevent rethrombosis after thrombolysis.
- Further clinical evaluation of calcium blockers as adjunctive therapy post-thrombolysis is warranted.
Abstract:
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.