Assessment of Long-term Benefit of Intensive Blood Pressure Control on Residual Life Span: Secondary Analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)

Abstract

Importance: High blood pressure (BP) is a leading contributor to premature mortality worldwide. The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated a 27% reduction in all-cause death with intensive (vs standard) BP control. However, traditional reporting of survival benefits is not readily interpretable outside medical communities.

Objective: To estimate residual life span and potential survival gains with intensive compared with standard BP control in the SPRINT trial using validated nonparametric age-based methods.

Design, setting, and participants: This secondary analysis of data from an open-label randomized clinical trial included data from 102 enrolling clinical sites in the United States. Adults who were 50 years or older, were at high cardiovascular risk but without diabetes, and had a screening systolic BP between 130 and 180 mm Hg were enrolled between November 2010 and March 2013. Data analysis occurred from May 2019 to December 2019.

Interventions: A 1:1 randomization to intensive (target, <120 mm Hg) or standard (target, <140 mm Hg) systolic BP targets.

Main outcomes and measures: We calculated age-based estimates of projected survival (at a given age) using baseline age rather than time from randomization as the time axis. In each treatment arm at every year of age, residual life span was estimated using the area under the survival curve, up to a maximum of 95 years. Differences in areas under the survival curves reflect the estimated treatment benefits on projected survival.

Results: A total of 9361 adults were enrolled (mean [SD] age at randomization, 68 [9] years; 6029 [64.4%] were men; 5399 [57.7%] were non-Hispanic white individuals). Mean survival benefits with intensive vs standard BP control ranged from 6 months to up to 3 years. At age 50 years, the estimated residual survival was 37.3 years with intensive treatment and 34.4 years with standard treatment (difference, 2.9 years [95% CI, 0.9-5.0 years]; P = .008). At age 65 years, residual survival was 24.5 years with intensive treatment and 23.3 years with standard treatment (difference, 1.1 years [95% CI, 0.1-2.1 years]; P = .03). Absolute survival gains with intensive vs standard BP control decreased with age, but the relative benefits were consistent (4% to 9%).

Conclusions and relevance: Intensive BP control improves projected survival by 6 months to 3 years among middle-aged and older adults at high cardiovascular risk but without diabetes mellitus. These post hoc actuarial analyses from SPRINT support the survival benefits of intensive BP control, especially among middle-aged adults at risk.

Trial registration: ClinicalTrials.gov Identifier: NCT01206062.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Vaduganathan serves on advisory boards for Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa. Dr Claggett has received consultancy fees from Boehringer Ingelheim, Gilead, AOBiome, and Corvia. Dr Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol-Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, the National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos and has consulted for Akros, Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Cardior, Corvia, Cytokinetics, Gilead, GlaxoSmithKline, Ironwood, Merck, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, and Cardiac Dimensions. No other disclosures were reported.

Figures

Figure 1.. Probability of Residual Survival in the Systolic Blood Pressure (BP) Intervention Trial (SPRINT) by Age at Randomization

Age-based Kaplan-Meier estimated curves are displayed for patients at age 50 years (A), 65 years (B), and 80 years (C) for survival between standard and intensive BP control arms. Residual life span was estimated using the area under the survival curve up to a maximum of 95 years.

Figure 2.. Long-term Benefit of Intensive Blood Pressure (BP) Control on Life Expectancy in the Systolic Blood Pressure Intervention Trial (SPRINT)

Estimated mean survival times (A) and event-free survival times (B) in the intensive BP control and standard BP control arms of SPRINT are displayed. Treatment differences and 95% CIs are estimated for mean survival (C) and event-free survival (D) after application of a locally weighted scatterplot-smoothing procedure.