JACC

Volume 86, Issue 17, 28 October 2025, Pages 1405-1417

Original Research
Effect of Intensive Blood Pressure Control on Stroke: A Prespecified Secondary Analysis of the ESPRIT Trial

https://doi.org/10.1016/j.jacc.2025年07月05日5 Get rights and content
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Abstract

Background

Elevated systolic blood pressure (SBP) accounts for one-half of the population attributable fraction for stroke, so lowering SBP is the most important treatment for preventing stroke.

Objectives

In this study, the authors sought to assess the effects of intensive treatment targeting SBP <120 mm Hg on stroke compared with standard treatment targeting SBP <140 mm Hg.

Methods

In the ESPRIT trial, hypertensive patients with high cardiovascular risk were randomly assigned to intensive treatment or standard treatment and followed for 3.4 years. We fitted Cox proportional hazards regression models to examine the effects on the incidence of stroke, one of the prespecified secondary outcomes. In addition, we performed post hoc analyses including effects on stroke subtypes and the landmark analyses about stroke and stroke subtypes.

Results

We randomized 11,255 participants (3,022 with previous stroke). Their mean age was 64.6 ± 7.1 years, and 4,650 (41.3%) were female. During the follow-up, the mean SBP was 119.1 ± 11.1 mm Hg in the intensive arm and 134.8 ± 10.5 mm Hg in the standard arm. Stroke occurred in 262 participants (4.7%) in the intensive arm and 303 (5.4%) in the standard arm (HR: 0.86; 95% CI: 0.73-1.02; P = 0.083), ischemic stroke in, respectively, 243 (4.3%) vs 261 (4.6%) (HR: 0.93; 95% CI: 0.78-1.11; P = 0.423), and hemorrhagic stroke 23 (0.4%) vs 45 (0.8%) (HR: 0.51; 95% CI: 0.31-0.85; P = 0.009). Landmark analysis showed that the risk difference in stroke emerged after 1 year, and the HR for the period of longer than 1 year was 0.75 (95% CI: 0.60-0.94; P = 0.011). There were no interactions across all subgroups of baseline characteristics, including demographics, region, lifestyle, diastolic blood pressure, orthostatic hypotension, and comorbidities (all P interaction >0.05).

Conclusions

Compared with targeting <140 mm Hg, targeting <120 mm Hg halved the risk of hemorrhagic stroke and did not increase that of ischemic stroke. The stroke-preventing effect emerged after 1 year of intervention. Future studies are needed to confirm these findings.

Key Words

hypertension
intensive blood pressure treatment
randomized clinical trial
stroke

Abbreviations and Acronyms

BP
blood pressure
DBP
diastolic blood pressure
eGFR
estimated glomerular filtration rate
SBP
systolic blood pressure

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The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
These authors are joint first authors.
© 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.