The Power of More Than One

Abstract

There is widespread recognition of the increasing challenge of conducting adequately powered clinical trials in cardiovascular medicine.1 Given the broadening gap between guideline-based recommendations and the level of evidence supported by trials, this matter is a central priority. Two fundamental properties characterize the contemporary assessment of cardiovascular clinical trials. First, they are generally designed to evaluate the time to first event between the study arms. Second, different clinical events, presumed to be related to the targeted disease of interest, are commonly combined to form a composite end point.2 This approach increases the number of events observed during follow-up, usually but not always enhancing the statistical power and efficiency of clinical trials (ie, reducing the number of patients required). Article see p 673 Despite these established analytic techniques, several potential liabilities exist. The first event within a composite end point may not reflect the most clinically important or relevant one. Thus, incorporating subsequent events seems rational to provide a more comprehensive perspective of disease burden or therapeutic efficacy. This would also be timely, given that the recognition of recurrent events has emerged as a matter of increasing interest to patients, healthcare investigators, providers, and payers. The interpretation of composite end points can be perplexing, particularly when the directions of the individual components differ.3 In this issue of Circulation , Kohli et al4 address recurrent multiple events in the recent Platelet Inhibition and Patient Outcomes (PLATO) trial. The PLATO trial definitively demonstrated a treatment benefit of ticagrelor compared with clopidogrel in the …