Study End PointsThe primary end poi

Study End Points
The primary end point was the occurrence of a major cardiovascular or renal event — a composite of death from cardiovascular or renal causes, stroke, myocardial infarction, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for permanent renal-replacement therapy. Myocardial infarction was adjudicated on the basis of the presence of clinical symptoms or electrocardiographic changes and elevated cardiac markers. Hospitalization for congestive heart failure was included in the analysis if the patient was hospitalized for 12 hours or longer because of documented signs and symptoms of heart failure and received intravenous therapy (vasodilators, diuretics, or inotropes) during the hospital stay. Progressive renal insufficiency was defined as a reduction from baseline of 30% or more in the estimated GFR, with the reduction sustained for 60 days or longer and not attributable to other causes. Secondary clinical end points included the individual components of the primary end point (with death from cardiovascular causes and death from renal causes as separate end points), as well as all-cause mortality. Complete definitions of the study end points are provided in the Supplementary Appendix. A single end-point committee whose members were unaware of the group assignments adjudicated all end points.
The definitions of end points were modified on March 12, 2012, by the CORAL steering committee, and the modifications were approved by the data and safety monitoring board and the FDA. These modifications, which were made before the data were unblinded and with the steering committee unaware of event rates in the study groups, were intended to bring the definitions of end points into alignment with clinical event definitions that had evolved during the course of the study. Details of the changes in end-point definitions are provided in Table S1 in the Supplementary Appendix.
Statistical Analysis
We originally calculated that 1080 participants would need to be enrolled for the study to have 90% power to test the hypothesis that stenting would reduce the incidence of the primary end point by 25% (hazard ratio, 0.75) at 2 years, at a two-sided type I error rate of 0.05. Because the recruitment was slower than anticipated, the data and safety monitoring board recommended termination of recruitment on January 30, 2010 (at which point 947 participants had undergone randomization), and follow-up was extended through September 28, 2012, to preserve the statistical power.
All the analyses were performed on an intention-to-treat basis. All participants who underwent randomization were included in the intention-to-treat analyses with the exception of the 16 participants (8 in each group) who were enrolled at a single site at which scientific integrity issues were identified; an administrative decision was made to exclude the data from these participants from the intention-to-treat analysis (see additional information below). Continuous variables are expressed as means and standard deviations and were compared with the use of Student's t-tests. Medians are presented with interquartile ranges. Categorical variables are expressed as proportions and were compared with the use of the chi-square test or Fisher's exact test, as appropriate. Time-to-event outcomes (including the primary end point) are expressed as Kaplan–Meier estimates and were compared between the treatment groups with the use of the log-rank statistic. The Cox proportional-hazards model was used to estimate the hazard ratios and associated 95% confidence intervals. Prespecified secondary analyses included tests for interaction effects between the primary end point and sex, race, presence or absence of diabetes, and presence or absence of global renal ischemia (defined as stenosis of 60% or more of the diameter of all arteries supplying both kidneys or stenosis of 60% or more of the diameter of all arteries supplying a single functioning kidney). The effect of treatment on systolic blood pressure over time was estimated with the use of a repeated-measures analysis.
The primary composite end point was tested at the 0.0497 level to adjust for a single interim analysis. All other analyses were performed at the 0.05 level without adjustment for multiple comparisons.