To the Editor: The Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation (CREATE)1 concludes that, in patients with acute ST-elevation myocardial infarction (STEMI), reviparin reduces overall mortality and reinfarction at 7 days (P = .005) and 30 days (P = .001). This is a megatrial involving 15 570 patients designed to detect a 15% relative risk (RR) reduction on the composite outcome at 7 days with a power of 93%. Although this conclusion is correct based on the applied analysis, it is important to examine the magnitude of the composite mortality reduction. The CREATE trial is similar to the Facile Interpretation of Statistical Hypotheses (FISH) trial postulated by Diamond and Kaul.2 The CREATE trial shows an absolute reduction in the first coprimary composite outcome at 7 days of 1.4%. Using a Bayesian approach with a noninformative prior (prior log odds ratio [OR] distribution with mean, 0 and SD, 10), as the CREATE trial was the first and only trial of this treatment that had been conducted, the posterior probability for more than 15% benefit is only 41%, whereas it is 95% for a threshold of benefit of 6%.
In addition, considering the 24 major bleeding events not included in the primary outcomes (17 reviparin and 7 placebo) and the same prior distribution, there is a 95% probability of a 12% increase in the RR of major bleeding in the reviparin group (OR, 2.3; 95% CI, 1.0-5.5; P = .05). Therefore, reading the CREATE study in terms of probability, it seems that patients treated in the reviparin group are 95% likely to have had a 6% RR reduction in the first composite outcome, and a 12% RR increase of life-threatening (nonfatal) bleeding.
The CREATE trial is significant because it demonstrates a “nonzero” positive benefit of low-molecular-weight heparin in myocardial infarction. However, it should not be considered conclusive and once again raises the debate between frequentist and Bayesian approaches, due to the large sample size and its influence on the P value.3 In megatrials, the frequentist approach cannot quantify the likelihood of detecting a significant effect. This is a real issue when the treatment under investigation has potentially dangerous adverse effects. In this case, previous studies on low-molecular-weight heparin could be used as prior distributions, helping to solve in a definitive way the risk-benefit ratio for the use of low-molecular-weight heparin. A Bayesian (meta) analysis of low-molecular-weight heparin as part of myocardial infarction treatment is now possible and advisable.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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