Thrombolysis has been shown to reduce mortality in several large placebo-controlled trials using streptokinase (SK) and tissue plasminogen activator (t-PA). These benefits persist through at least 10 years of follow up. The Fibrinolytic Therapy Trialists' overview of all the major placebo-controlled studies showed a 2.6% absolute reduction in mortality for patients who have STEMI treated within the first 12 hours after the onset of symptoms [53]. Patients presenting with new left bundle branch block and a strong clinical history for acute MI also derive a substantial benefit from thrombolysis. Patients who have non-ST

elevation ACS, however, do not benefit from thrombolysis.

SK was the initial fibrinolytic drug, with newer agents later developed. The fibrin-specific thrombolytic agents, such as alteplase (t-PA), were seen in the TIMI-1 trial to have twice the rate of infarct-related artery patency as SK [54]. In the GUSTO I trial, accelerated tPA plus heparin led to a highly significant 14% reduction in mortality. Reteplase and tenecteplase are molecular modifications of t-PA designed to have longer plasma half-lives that allow double or single bolus administration, respectively. However, the newer agents did not lead to a further reduction in mortality rates compared with t-PA.

Similarly, use of the combination of half-dose fibrinolysis and GP IIb/IIIa receptor inhibitors did not improve mortality, and this more complicated regimen is not widely used. The use of other adjunctive agents with full-dose fibrinolysis is being actively studied, with enoxaparin being compared with UFH in the EXTRACT-TIMI 25 trial, and clopidogrel being added to standard regimens versus placebo in the CLARITY-TIMI 28 trial.

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