Geographic variability in outcomes within an international trial of glycoprotein IIb/IIIa inhibition in patients with acute coronary syndromes - Results from PURSUIT

Aims Variations in outcome of patients from different geographic regions ha ve been observed in many large international trials. We analysed the factor s that might contribute to the geographic variations in patient outcome and treatment effect as observed in the PURSUIT trial. Methods In PURSUIT, 9461 patients with acute coronary syndromes without per sistent ST-elevation were randomized to the platelet inhibitor eptifibatide or placebo for 72 h in 27 countries in four geographic regions: Western (n =3697) and Eastern Europe (n=1541) as well as North (n=3827) and Latin Amer ica (n=396). The primary endpoint was the 30-day composite of death or myoc ardial infarction. In the initial univariate analysis, the treatment effect appeared greater in N. America than in W. Europe, while no benefit was app arent in L. America and E. Europe. However, the confidence intervals were w ide and overlapping. To study these differences, a subdivision in an early and late patient outcome and treatment effect was made. Accordingly, we ana lysed the rate of death or infarction at 72 h censored for percutaneous cor onary intervention and the rate between 3 and 30 days, respectively. Additi onal analyses were performed with different definitions of myocardial infar ction using-progressively higher thresholds of CK(-MB) elevation. Multivari able analysis was used to evaluate the relation between region and outcome and to determine the adjusted odds ratios for the eptifibatide treatment ef fect. Results Major differences in baseline demographics were apparent among the four regions; in particular, more patients from E. Europe had characteristi cs associated with impaired outcome. Interventional treatment also varied c onsiderably, with more patients from N. America undergoing revascularizatio n. Despite differences in the 72 h event rate, eptifibatide showed a consis tent trend towards a reduction in the composite end-point among all four re gions and for all definitions of infarction. Relative reductions ranged fro m 17-42% in W. Europe, 23-35% in N. America, 0-33% in E. Europe, and 55-82% in L. America. After multivariable adjustment, the pattern of benefit with eptifibatide was consistent among the regions. In patients undergoing perc utaneous coronary intervention during study drug infusion in W. Europe (n=2 66) and N. America (n=931), the relative reduction in myocardial infarction during medical therapy ranged from 56-75% in W. Europe and 14-67% in N. Am erica, while the reduction in procedure-related events ranged from 12-44% a nd 25-61% for different definitions of infarction. After multivariable adju stment neither benefit nor rebound were apparent after study drug discontin uation, or after 3 days in all regions, except in L. America. In general, t he differences in outcome and treatment effect were greatest when the proto col definition of myocardial infarction (CK(-MB) >1 upper normal limit) was applied. Under stricter definitions, these differences became smaller and disappeared with the investigator's assessment. Conclusion The analysis suggests that the apparent differences in patient o utcome and eptifibatide treatment effect can be explained largely by differ ences in baseline demographics and adjunctive treatment strategies as well as by the methodology of myocardial infarction definition and the adjudicat ion process. (C) 2000 The European Society of Cardiology.