The original composite primary end point consisted of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, or high-risk acute coronary syndrome.14 Because the rate of the primary end point was lower than projected, the protocol was amended to change the end point of “high-risk acute coronary syndrome” to include hospitalization for an acute coronary syndrome and symptom-driven coronary
or cerebral revascularization, on the basis of a blinded examination of data by the executive committee; an independent review committee appointed by the NHLBI, whose members did not have access to data on treatment-specific results, reviewed and recommended approval of this amendment in March 2010. In this event-driven trial, we expected to observe 800 adjudicated primary events during a mean follow-up period of 4.6 years. With this number of events, we estimated that the study would have 85% power to detect a 25% reduction in the revised five-component primary end point, at a one-sided alpha level of 0.025. A formal interim analysis plan specified asymmetric boundaries for stopping the trial early on the basis of a demonstration of efficacy or lack of efficacy. The boundary for lack of efficacy required an observed hazard ratio of 1.02 or greater with a P value for futility of less than 0.001 when 50% of events were reported. The follow-up period was scheduled to end in December 2012. At a meeting on April 25, 2011, the data and safety monitoring board recommended that the blinded intervention be stopped because the boundary for lack of efficacy had been crossed and an unexpected higher rate of ischemic stroke had been observed among patients who were being treated with niacin; the NHLBI accepted that recommendation.