Poor outcomes after fibrinolytic therapy for ST-segment elevation myocardial infarction: Impact of age (A meta-analysis of a decade of trials)

Background: Fibrinolysis for ST-segment elevation myocardial infarction (STEMI) reduces mortality, but its relative efficacy and risks are age-dependent. We aimed to quantify the outcomes of fibrinolysis and adjunctive antithrombin therapy for STEMI stratified by age. Methods: We performed a meta-analysis of 11 published ( 1992 - 2001) randomized clinical trials of fibrinolysis in STEMI ( sample size >= 3000, no age limit, no placebo-controlled arms) identified by MEDLINE through June 2005. Event rates and odds ratios ( OR) in elderly vs. younger patients were calculated for mortality, intracranial hemorrhage (ICH) and total stroke (CVA). Elderly patients were defined as >= 75 years ( GUSTO I, TIMI 9B, GUSTO III, COBALT, ASSENT-2, InTIME-II TIMI-17, ASSENT-3, GUSTO V, and HERO-2), except when defined as > 65 or >= 70 years by the study ( INJECT and ISIS-3). Results: Elderly ( n = 24 531) vs. younger ( n = 123 568) patients had increased rates of mortality (19.7% vs. 5.5%), ICH (1.4% vs. 0.5%) andCVA(3.5 vs. 1.2%) by 30 - 35 days; the excess risk for these events was substantial ( OR mortality 4.37, 95% CI 4.16 - 4.58; ICH 2.83, 2.47 - 3.24; CVA 2.92, 2.62 - 3.25; p< 0.001 for all). Conclusions: Despite established mortality reductions with fibrinolysis for STEMI, elderly compared with younger patients, still have a three to four fold increased risk of mortality and adverse events when treated with fibrinolysis and antithrombin therapy in the modern era. These robust estimates of the anticipated rates for mortality, ICH, and CVA can be used as benchmarks to monitor the efficacy and safety of therapies in ongoing and newly completed clinical trials.