The Effect of Frailty on the Efficacy and Safety of Intensive Blood Pressure Control: A Post Hoc Analysis of the SPRINT Trial

Frailty is associated with an increased risk of all-cause death and cardiovascular events. However, it is uncertain whether frailty modifies the efficacy and safety of intensive blood pressure control.Data from SPRINT (Systolic Blood Pressure Intervention Trial) were used to construct a frailty index. Subgroup differences in intensive blood pressure control treatment effects and safety outcomes were measured on a relative and an absolute scale in patients with and without frailty (defined as a frailty index >0.21) using Cox proportional hazard models and generalized linear models, respectively. The primary outcome was a composite of myocardial infarction, acute coronary syndrome without myocardial infarction, stroke, heart failure, and cardiovascular death.A total of 9306 patients (mean age, 67.9±9.4 years), 2560 (26.7%) of whom had frailty, were included in our study. Over a median follow-up of 3.22 years, 561 primary outcomes were observed. Patients with frailty had a significantly higher risk of primary outcome in both the intensive and standard blood pressure control arms (adjusted hazard ratio, 2.10 [95% CI, 1.59-2.77] and 1.85 [95% CI, 1.46-2.35], respectively). Intensive treatment effects on primary and secondary outcomes were not significantly different on a relative scale (except for cardiovascular death [hazard ratio in patients with and without frailty, 0.91 (95% CI, 0.52-1.60) versus 0.30 (95% CI, 0.16-0.59), respectively; Pinteraction=0.01]) or absolute scale. There was no significant interaction between frailty and risks for serious adverse events with intensive treatment.Frailty status was a marker of high cardiovascular risk. Patients with frailty benefit similarly to other patients from intensive blood pressure control without an increased risk of serious adverse events.