Thrombolysis for Acute Myocardial Infarction: Drug Review

David K. Cundiff

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In This Article

The Aspirin Factor

In the 9 major trials of thrombolytic agents vs standard treatment for AMI, which established the role of thrombolytic therapy, all patients received aspirin in 4 trials and half of the patients took it in ISIS-2, where aspirin allocation was random. Of all randomized trials of anticoagulants for AMI since the 1970s, only ISIS-2 looked at aspirin and thrombolysis independently and in combination. Aspirin or another antiplatelet drug alone provides an unknown portion of the overall reduction in mortality when combined with thrombolytic agents, but aspirin causes almost none of the toxicity or expense. Given these comparisons, evidence of an additional survival benefit of thrombolysis above that of aspirin depends entirely on ISIS-2 and whether ISIS-2 data is consistent with findings of the other trials.

ISIS-2 randomized 17,187 patients with suspected AMI, comparing aspirin, SK, both, and neither (Table 1).[10] This study reported that aspirin decreased the odds of death in 5 weeks in the aspirin arm by 23% (24 per 1000 patient deaths prevented), SK reduced it by 25% (28 per 1000 patient deaths prevented), and both together by 42% (52 per 1000 patient deaths prevented).[10] The relative efficacy of aspirin and thrombolysis on AMI mortality in ISIS-2 differs considerably from those of the meta-analyses of the aspirin and thrombolysis trials. The mortality reduction in the meta-analysis of aspirin vs placebo studies (approximately 20,000 patients studied; survival benefit = 29% [about 40/1000 deaths prevented][20]) exceeds that of the meta-analysis of thrombolysis trials (58,511 patients studied; survival benefit = 18% [about 20/1000 deaths prevented][19]). Omitting ISIS-2 from the meta-analysis gives a survival benefit of 13% (about 15/1000 deaths prevented). Consequently, it doesn't matter what thrombolytics do to AMI mortality compared with placebo. The question is what thrombolytics do to AMI mortality compared with aspirin.

Comparing the mortality in the fibrinolysis studies that did not routinely include aspirin (Table 2) vs those trials in which all patients received aspirin (Table 3) shows a striking difference in efficacy of thrombolysis. Table 4 shows that ISIS-2 and the studies that did not include routine aspirin account for virtually all of the meta-analysis' statistical significance concerning a survival advantage with fibrinolysis in AMI. The 21,144 patients randomized in studies including routine aspirin demonstrate no significant survival advantage with fibrinolysis (P = .14).

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