Effect of Intensive Blood Pressure Treatment on Heart Failure Events in the Systolic Blood Pressure Reduction Intervention Trial

Abstract

Background: Acute decompensated heart failure (ADHF) was a frequent common outcome in SPRINT (Systolic Blood Pressure Intervention Trial). We examined whether there was differential reduction in ADHF events from intensive blood pressure [BP] treatment among the 6 key, prespecified subgroups in SPRINT: age ≥75 years, prior cardiovascular disease, chronic kidney disease, women, black race, and 3 levels of baseline systolic BP (≤132 versus >132 to <145 versus ≥145 mm Hg).

Methods and results: ADHF was defined as hospitalization for ADHF, confirmed and formally adjudicated by a blinded events committee using standardized protocols. At 3.29 years follow-up, there were 103 ADHF events (2.2%) among 4683 standard arm participants and 65 ADHF events (1.4%) among 4678 intensive arm participants (Cox proportional hazards ratio, 0.63; 95% confidence interval, 0.46-0.85; P value =0.003). In multivariable analyses, including treatment arm, baseline covariates that were significant predictors for ADHF included chronic kidney disease, cardiovascular disease, age≥75 years, body mass index, and higher systolic BP. The beneficial effect of the intervention on incident ADHF was consistent across all prespecified subgroups. Participants who had incident ADHF had markedly increased risk of subsequent cardiovascular events, including a 27-fold increase (P<0.001) in cardiovascular death.

Conclusions: Targeting a systolic BP<120 mm Hg, compared with <140 mm Hg, significantly reduced ADHF events, and the benefit was similar across all key, prespecified subgroups. Participants who developed ADHF had markedly increased risk for subsequent cardiovascular events and death, highlighting the importance of strategies aimed at prevention of ADHF, especially intensive BP reduction.

Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.

Keywords: aging; clinical trial; heart failure; hypertension; women and minorities.

Conflict of interest statement

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Kitzman reported receiving personal fees from Merck, Forest Labs, and Abbvie; personal fees and other from Gilead and Relypsa; and grants from Novartis outside the submitted work. Dr Oparil reported receiving personal fees from Forest Laboratories Inc; grants, personal fees, and nonfinancial support from Medtronic; personal fees from Amgen (Onyx is subsidiary); grants and personal fees from AstraZeneca and Bayer Healthcare Pharmaceuticals Inc; personal fees from Boehringer-Ingelheim and GlaxoSmithKline; grants from Merck and Co; and serving as co-chair for the Eighth Joint National Committee. Dr. Lewis reported research funding from Novo Nordisk. Dr. Cushman reported receiving institutional grants from Eli Lilly and Boehringer Ingelheim, and has provided uncompensated consultation to Takeda Pharmaceuticals. No other disclosures were reported.

© 2017 American Heart Association, Inc.

Figures

Figure 1

Kaplan-Meier curves for the SPRINT acute decompensated heart failure outcome by treatment group. Vertical bars indicate 95% confidence intervals. P-value is from a Cox proportional hazards model stratified by clinical site. Number at risk and number of events is shown every six months.

Figure 2

Forest plot of acute decompensated heart failure according to subgroups. The dashed vertical line represents the hazard ratio for the overall study population. The box sizes are proportional to the precision of the estimates (with larger boxes indicating a greater degree of precision). The subgroup of no previous chronic kidney disease (CKD) includes some participants with unknown CKD status at baseline. Black race includes Hispanic black and black as part of a multiracial identification.