Thrombolysis for acute myocardial infarction: drug review

The proof of efficacy of thrombolysis for acute myocardial infarction (AMI) depends on 9 randomized placebo-controlled trials totaling 58,511 patients. The meta-analysis of these trials showed an overall survival advantage of about 2% (11.5% vs 9.6%) in favor of thrombolysis. Iatrogenic deaths from thrombolysis complications occur in about 1% of AMI patients. Timely opening of the infarct-related artery (IRA) allowing myocardial reperfusion has been proposed to explain any survival advantage seen with thrombolysis ("open-artery hypothesis"). Angiographic data does not support the open-artery hypothesis as the mechanism of any benefit of thrombolysis. The "early hazard" (ie, increased mortality in the first 12 hours after thrombolysis) also suggests that the supposed survival benefit is due to something other than early reperfusion. The variable use of aspirin in the meta-analysis trials may have confounded the results and conclusions. In the 4 studies of the meta-analysis in which aspirin was used routinely (n = 21,144), the survival benefit was not statistically significant (P =.14). Lack of blinding in some studies and other methodologic problems may also call the conclusions of the meta-analysis into question. AMI registry reports comparing patients with and without thrombolysis have not borne out a significant survival advantage with thrombolysis. The National Registry of Myocardial Infarction (NRMI) registry data suggest that a significant number of AMI patients may be inappropriately receiving thrombolytics. An independent analysis of the NRMI mortality data adjusted for age and other risk factors would help determine whether thrombolysis for AMI improves survival.