Comparative case fatality analysis of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial: Variation by country beyond predictive profile

Abstract

Objectives. This study was designed to examine the variation in mortality rates among countries participating in the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.Background. Despite uniform inclusion and exclusion criteria and protocol in this trial, 30-day mortality rates (irrespective of treatment allocation) ranged from 4.2% to 14.8% among the participating countries.Methods. With use of the risk factors identified by a multivariate logistic model, the total study group was classified into deciles on the basis of each patient's risk profile and Individual probability of dying within 30 days. Expected mortality rates were then calculated and compared with actual mortality for each decile of the total study group, as well as for patients from each country.Results. Independent risk factors for mortality were older age (odds ratio 1.97 for each 10-year increment), systolic hypotension (blood pressure <95 mm Hg) at entry (odds ratio 3.7), Killip class >1 at entry (odds ratio 3.5), history of antecedent angina (odds ratio 1.23 to 1.49), history of diabetes mellitus (odds ratio 1.64), previous infarction (odds ratio 1.23) and history of never smoking (odds ratio 1.37).The overall mortality rate among the 1, 612 patients in risk deciles 9 and 10 was 26%; for the 1, 606 patients in deciles 1 and 2 it was 1.2%, with a sensitivity of 58.6% and a specificity of 83.7%. The logistic model closely predicted and explained the different mortality rates for most countries (the differences between expected and actual mortality were nonsignificant), However, in the total study group, the difference between the expected and actual mortality was significant (p < 0.001). This difference was mainly ascribed to the two countries with the highest and lowest mortality rates. When the patients from these two countries were excluded from the analysis, the overall difference became nonsignificant.Conclusions. These findings suggest that the recognized risk factors associated with increased case fatality in acute myocardial infarction account only in part for mortality differences across or within populations.