Identifying Patients for Intensive Blood Pressure Treatment Based on Cognitive Benefit: A Secondary Analysis of the SPRINT Randomized Clinical Trial

IMPORTANCE: Intensive vs standard treatment to lower systolic blood pressure (SBP) reduces risk of mild cognitive impairment (MCI) or dementia; however, the magnitude of cognitive benefit likely varies among patients. OBJECTIVE: To estimate the magnitude of cognitive benefit of intensive vs standard systolic BP (SBP) treatment. DESIGN, SETTING, AND PARTICIPANTS: In this ad hoc secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), 9361 randomized clinical trial participants 50 years or older with high cardiovascular risk but without a history of diabetes, stroke, or dementia were followed up. The SPRINT trial was conducted between November 1, 2010, and August 31, 2016, and the present analysis was completed on October 31, 2022. INTERVENTION: Systolic blood pressure treatment to an intensive (<120 mm Hg) vs standard (<140 mm Hg) target. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of adjudicated probable dementia or amnestic MCI. RESULTS: A total of 7918 SPRINT participants were included in the analysis; 3989 were in the intensive treatment group (mean [SD] age, 67.9 [9.2] years; 2570 [64.4%] men; 1212 [30.4%] non-Hispanic Black) and 3929 were in the standard treatment group (mean [SD] age, 67.9 [9.4] years; 2570 [65.4%] men; 1249 [31.8%] non-Hispanic Black). Over a median follow-up of 4.13 (IQR, 3.50-5.88) years, there were 765 and 828 primary outcome events in the intensive treatment group and standard treatment group, respectively. Older age (hazard ratio [HR] per 1 SD, 1.87 [95% CI, 1.78-1.96]), Medicare enrollment (HR per 1 SD, 1.42 [95% CI, 1.35-1.49]), and higher baseline serum creatinine level (HR per 1 SD, 1.24 [95% CI, 1.19-1.29]) were associated with higher risk of the primary outcome, while better baseline cognitive functioning (HR per 1 SD, 0.43 [95% CI, 0.41-0.44]) and active employment status (HR per 1 SD, 0.44 [95% CI, 0.42-0.46]) were associated with lower risk of the primary outcome. Risk of the primary outcome by treatment goal was estimated accurately based on similar projected and observed absolute risk differences (C statistic = 0.79). Higher baseline risk for the primary outcome was associated with greater benefit (ie, larger absolute reduction of probable dementia or amnestic MCI) of intensive vs standard treatment across the full range of estimated baseline risk. CONCLUSIONS AND RELEVANCE: In this secondary analysis of the SPRINT trial, participants with higher baseline projected risk of probable dementia or amnestic MCI gained greater absolute cognitive benefit from intensive vs standard SBP treatment in a monotonic fashion. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062