Characteristics and mortality outcomes of thrombolysis trial participants and nonparticipants: a population-based comparison

Abstract

Objectives: This study was done to compare characteristics and outcomes of patients with acute myocardial infarction participating in two thrombolysis trials with those of nontrial patients at study hospitals and external hospitals.

Background: Preferential recruitment of lower risk 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 thrombolysis trial participants and nonparticipants.

Methods: Population-based data on hospital admissions and mortality from acute myocardial infarction 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, comorbidity scores, coronary revascularization and survival to hospital discharge.

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 scores (OR 2.0 and 2.3, respectively) and, for GUSTO alone, to undergo coronary revascularization (OR 2.4). Nontrial patients were similar between trial hospitals and external hospitals. In-hospital mortality rates for GUSTO and LATE patients were lower (6.9% and 6.6%, respectively) than for nonparticipants at study hospitals (16.8% and 19.7%, respectively; p<0.001 for both comparisons). Survival to hospital discharge remained higher among GUSTO (OR 1.9) and LATE patients (OR 2.0) than nonparticipants at study hospitals even after adjustment for age, gender, revascularization and comorbidity scores.

Conclusions: Compared with nontrial patients, thrombolysis trial participants are younger, more 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 from thrombolysis alone. These findings are not attributable to inferior care or skewed populations at hospitals that did not join these major trials. Further study of these selection biases may guide future trial design and deepen our understanding of why thrombolytics have been underused for high risk patients in routine practice.