CHARACTERISTICS AND MORTALITY OUTCOMES OF THROMBOLYSIS TRIAL PARTICIPANTS AND NONPARTICIPANTS - A POPULATION-BASED COMPARISON

Objectives. This study was done to compare characteristics and outcome s of patients with acute myocardial infarction participating in two th rombolysis trials with those of nontrial patients at study hospitals a nd external hospitals. Background. Preferential recruitment of lower r isk patients into randomized trials of thrombolysis has been suggested by earlier studies. However, to date there has not been a definitive population-based comparison of characteristics and outcomes for thromb olysis trial participants and nonparticipants. Methods. Population-bas ed data on hospital admissions and mortality from acute myocardial inf arction for all hospitals in Ontario from 1989 to 1992 were linked to data on trial participants in two distinct thrombolysis studies (GUSTO I and LATE). Included were 1,304 patients entered into GUSTO, 12,657 nonparticipants at GUSTO hospitals, 249 patients entered into LATE, 5, 997 nonparticipants at LATE hospitals and 12,299 patients at external hospitals. The main outcomes were differences in age, gender, comorbid ity scores, coronary revascularization and survival to hospital discha rge. Results. Patients in both GUSTO and LATE were significantly more likely to be <70 years old (odds ratio [OR] 2.8 and 3.2, respectively) , to be male (OR 2.0 and 2.1, respectively), to have low comorbidity s cores (OR 2.0 and 2.3, respectively) and, for GUSTO alone, to undergo coronary revascularization (OR 2.4). Nontrial patients were similar be tween trial hospitals and external hospitals. In-hospital mortality ra tes for GUSTO and LATE patients mere lower (6.9% and 6.6%, respectivel y) than for nonparticipants at study hospitals (16.8% and 19.7%, respe ctively; p < 0.001 for both comparisons). Survival to hospital dischar ge remained higher among GUSTO (OR 1.9) and LATE patients (OR 2.0) tha n nonparticipants at study hospitals even after adjustment for age, ge nder, revascularization and comorbidity scores. Conclusions. Compared with nontrial patients, thrombolysis trial participants are younger, m ore often male, undergo more revascularization and have less comorbid disease. Even after adjustment for these factors, participants have a survival advantage over nonparticipants that is larger than expected f rom thrombolysis alone. These findings are not attributable to inferio r care or skewed populations at hospitals that did not join these majo r trials. Further study of these selection biases mag guide future tri al design and deepen our understanding of why thrombolytics have been underused for high risk patients in routine practice.