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[Different therapeutic regimens in thrombolysis of acute myocardial infarct]
1Städtische Kliniken Kassel, Medizinische Klinik II.
Insights
Early artery opening with thrombolytic therapy improves survival in heart attack patients. Novel drug combinations and adjunctive treatments like heparin and hirudin show promise for optimal outcomes.
Area of Science:
- Cardiology
- Pharmacology
Context:
- Acute myocardial infarction (AMI) management relies on rapid restoration of infarct artery patency.
- Thrombolytic therapy is crucial for reducing mortality in AMI patients.
Purpose:
- To review the efficacy of various thrombolytic agents and adjunctive therapies in achieving early and sustained infarct artery patency.
- To explore novel thrombolytic regimens and their impact on patient outcomes.
Summary:
- Early patency of the infarct-related artery via thrombolysis reduces mortality in acute myocardial infarction.
- While ISIS-3 showed no mortality difference between t-PA, APSAC, and streptokinase, GUSTO-trial demonstrated reduced in-hospital mortality with front-loaded t-PA.
- Newer regimens like double-bolus t-PA and r-PA achieve high patency rates; adjunctive heparin and hirudin show potential in reducing reocclusions and reinfarctions.
Impact:
- Optimal thrombolysis likely requires a combination of highly effective lytic agents and adjunctive antiplatelet and antithrombin therapies.
- Improved therapeutic strategies can lead to better survival rates and reduced complications in AMI patients.
Abstract:
An early, complete, and sustained patency of the infarct related artery achieved by thrombolytic therapy reduces mortality in patients with acute myocardial infarction. In the ISIS-3-study there was no difference in mortality between t-PA, APSAC, and streptokinase. In contrast, in the GUSTO-trial, a "front-loaded" regimen of t-PA (100 mg/90 min) lead to a reduced inhospital mortality compared to streptokinase. This was most likely due to the higher early patency-rate of the infarct-related artery after the front-loaded t-PA. The search for new, more effective, thrombolytic regimens lead to a double-bolus injection of t-PA (2 x 50 mg) which revealed high early patency rates (> 80% TIMI-3 after 90 min). R-PA, a new recombinant plasminogen activator with a prolonged half-life, given as double bolus (2 x 10 MU), also produced high patency rates after 90 min without an increased incidence of reocclusions. Acetylsalicylic acid should be given routinely in every thrombolytic therapy. An anticoagulation with heparin seems to improve the efficacy of the more fibrin-specific thrombolytics t-PA, r-PA, and pro-urokinase. In dose-finding studies the specific thrombin inhibitor hirudin has been shown to significantly reduce reocclusions and reinfarctions compared to heparin. An "optimal thrombolysis" most likely can only be achieved by a thrombolytic agent with a very high early patency combined with an effective adjunctive therapy with platelet aggregation- and thrombin-inhibition.