Patient-Profiled Treatment Responses and Cardiac Endpoint Prevention in the Value Outcome Trial

Objective: Although many hypertension outcome trials have shown the benefit of treating hypertensive patients, subgroup analyses to explore the effects of treatment in relation to certain patient characteristics are limited. Whenever subgroup analyses of major hypertension trials are available, these are usually based on one factor at the time and not on a more comprehensive patient profile. We hypothesized that blood pressure (BP) responses and cardiovascular events differ significantly between patient profiles that are constructed by a combination of individual predictors. Design and method: To test our hypothesis, we reanalysed the data from the double-blinded VALUE-outcome trial (n=15.313) and randomly divided the patient population (2:1) into an exploration and a validation cohort. We constructed composite patient profiles based on the combination of four proven predictors of BP control (age, severity of hypertension, comorbidity and previous treatment status). Next, we tested in the exploration cohort whether blood pressure control (BPC) after six months of therapy among these profiles differed from those in the entire patient group. We also determined to what extent the various profiles were related to primary cardiac events. Finally, we explored whether the results from the exploration cohort could be validated in the other cohort. Only profiles containing 50 or more patients were used. Results: Of the 121 profiles identified in the trial, 36 had enough patients for analysis. Logistic regression analysis showed that the odds of reaching BPC control differed substantially between these profiles, regardless of treatment (figure 1). Six profiles performed better than average and seven worse. Similar trends were noted for the incidence of cardiac events. Some profiles, notably those containing diabetes, were associated with an increased incidence of events, even in patients with adequate BPC. All results were corroborated in the validation cohort (figure 2).Conclusions: We conclude that responses to antihypertensive treatment and the incidence of cardiac events vary in a clinically important way depending upon composite patient profiles. This knowledge may help choosing the best treatment in individual patients to improve overall BP control rates.