OBJECTIVE: To examine differences in outcomes and patient management between patients in the United States and outside the United States undergoing thrombolysis for acute myocardial infarction. DESIGN, SETTING, AND PATIENTS: Patients in the United States (n = 23,105) and 14 other countries (n = 17,916) were randomized to receive streptokinase plus either subcutaneous or intravenous (IV) heparin, accelerated recombinant tissue-type plasminogen activator (rt-PA) plus IV heparin, or combined streptokinase and rt-PA plus IV heparin. OUTCOME MEASURES: Differences in 30-day mortality and patient management were compared among treatments and between US and non-US patients. Treatment-by-country interactions were assessed by logistic regression analyses. Expected mortality of US and non-US patients was estimated using a predictive model and was compared with observed mortality. RESULTS:Mortality reduction with accelerated rt-PA vs streptokinase was greater in the United States (1.2% absolute decrease vs 0.7% elsewhere), but the test for treatment-by-country interaction against streptokinase was not significant (P = .30). Benefits of accelerated rt-PA over combination therapy were observed in the United States, but not in other countries (P = .02). Despite differences in base-line characteristics and patient management, 30-day mortality was not significantly different: 6.8% in the United States vs 7.2% elsewhere (P = .09). After adjustment for baseline differences, observed vs predicted outcomes were slightly better in the United States (6.8% vs 7.0%) than elsewhere (7.2% vs 7.0%), indicating that enrollment in the United States was a marginally significant predictor of better survival (P = .047). CONCLUSIONS: No significant evidence for a differentially greater benefit of accelerated rt-PA over streptokinase was found in US vs non-US patients. However, increased procedure and treatment use in the United States was associated with only a small decrease in short-term mortality. Long-term follow-up is required to clarify the relationship between survival and the more intensive US management approach.
RCT Entities:
OBJECTIVE: To examine differences in outcomes and patient management between patients in the United States and outside the United States undergoing thrombolysis for acute myocardial infarction. DESIGN, SETTING, AND PATIENTS: Patients in the United States (n = 23,105) and 14 other countries (n = 17,916) were randomized to receive streptokinase plus either subcutaneous or intravenous (IV) heparin, accelerated recombinant tissue-type plasminogen activator (rt-PA) plus IV heparin, or combined streptokinase and rt-PA plus IV heparin. OUTCOME MEASURES: Differences in 30-day mortality and patient management were compared among treatments and between US and non-US patients. Treatment-by-country interactions were assessed by logistic regression analyses. Expected mortality of US and non-US patients was estimated using a predictive model and was compared with observed mortality. RESULTS: Mortality reduction with accelerated rt-PA vs streptokinase was greater in the United States (1.2% absolute decrease vs 0.7% elsewhere), but the test for treatment-by-country interaction against streptokinase was not significant (P = .30). Benefits of accelerated rt-PA over combination therapy were observed in the United States, but not in other countries (P = .02). Despite differences in base-line characteristics and patient management, 30-day mortality was not significantly different: 6.8% in the United States vs 7.2% elsewhere (P = .09). After adjustment for baseline differences, observed vs predicted outcomes were slightly better in the United States (6.8% vs 7.0%) than elsewhere (7.2% vs 7.0%), indicating that enrollment in the United States was a marginally significant predictor of better survival (P = .047). CONCLUSIONS: No significant evidence for a differentially greater benefit of accelerated rt-PA over streptokinase was found in US vs non-US patients. However, increased procedure and treatment use in the United States was associated with only a small decrease in short-term mortality. Long-term follow-up is required to clarify the relationship between survival and the more intensive US management approach.