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

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.

Objective: 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.

Keywords: hypertension; intensive blood pressure treatment; randomized clinical trial; stroke.