Predictors of medical events in patients enrolled in the Cardiac Insufficiency Bisoprolol Study (CIBIS): A study of the interactions between beta-blocker therapy and occurrence of critical events using analysis of competitive risks

Background The risk of occurrence of medical events in a clinical trial is competitive in nature; that is, in a given patient the risk of having a cri tical event depends on the amount of time elapsed since random assignment a nd on the previous events that may have occurred in the patient. The purpos e of this study was to examine the relations between baseline variables, th e interactions between treatment, bisoprolol, or placebo, and the occurrenc e of critical events during the CIBIS trial, a mortality and morbidity tria l of beta-blockade in patients with heart failure. Methods and Results A Cox model for censored data was used to analyze the r elations between baseline variables, total deaths, permanent treatment with drawals, nonlethal cardiovascular events, and their interactions with bisop rolol or placebo. We examined the influence of treatment on the occurrence of deaths, permanent treatment withdrawals, and nonlethal cardiovascular ev ents by using the technique of event history analysis, which takes into acc ount competitive risks between events. Compared with placebo, bisoprolol re duced mortality rates in patients with a left ventricular election fraction less than or equal to 20% (relative risk [RR] 0.49; 95% confidence interva l [CI] 0.27 to 0.88; P = .02). In patients whose baseline heart rate was in the upper tertile of distribution, permanent treatment withdrawals were le ss frequent in patients randomly assigned to bisoprolol than in patients ra ndomly assigned to placebo (RR 0.50; 95% CI 0.28 to 0.88; P = .02). Bisopro lol reduced the incidence of nonlethal cardiac events in patients in whom h eart failure was present for at least 4 years (RR 0.44; 95% CI 0.27 to 0.71 ; P < .01). Event history analysis revealed that among patients who died un der treatment after having at least 1 nonlethal cardiovascular event, 20 pa tients were treated with placebo but only 7 patients were treated with biso prolol (RR 0.41; 95% CI 0.17 to 0.98; P < .05). Conclusions some patients with heart failure derive more benefit from beta- blocker therapy than others. In the CIBIS trial, they are those patients wi th the lower left ventricular ejection fractions and those who have nonleth al cardiovascular events but in whom beta-blocker therapy is not permanentl y discontinued.