ESPRIT - Intensive Blood Pressure Control on Stroke
Effect of Intensive Blood Pressure Control on Stroke: A Prespecified Secondary Analysis of the ESPRIT Trial
Clinical Question
Does intensive systolic blood pressure lowering to <120 mmHg reduce stroke risk compared to standard treatment targeting <140 mmHg in hypertensive patients with high cardiovascular risk?
Study Overview
Objective
To assess the effects of intensive treatment targeting SBP <120 mm Hg on stroke compared with standard treatment targeting SBP <140 mm Hg
Study Summary
- Intensive SBP control (<120 mmHg) halved hemorrhagic stroke risk (HR 0.51, 95% CI 0.31-0.85, P=0.009) vs standard control (<140 mmHg)
- Overall stroke reduction was nonsignificant (4.7% vs 5.4%, HR 0.86, 95% CI 0.73-1.02, P=0.083)
- Stroke prevention benefit emerged after 1 year of treatment (HR 0.75, 95% CI 0.60-0.94, P=0.011)
Intervention
Intensive arm: SBP target <120 mmHg with attended office BP measurement; Standard arm: SBP target <140 mmHg. Both arms used unified treatment algorithms; participants were followed up at 1, 2, and 3 months and then every 3 months, with antihypertensive medications adjusted by investigators based on measured BP and study-arm assignment.
Patients per Arm
Intensive: 5,624; Standard: 5,631
Bottom Line
Intensive SBP control halved the risk of hemorrhagic stroke and did not increase ischemic stroke risk. The stroke prevention benefit emerged after 1 year of intervention.
Major Points
- Intensive SBP control (<120 mmHg) reduced hemorrhagic stroke by 49% (HR 0.51, 95% CI 0.31-0.85, P=0.009)
- Overall stroke reduction was 14% but not statistically significant (HR 0.86, 95% CI 0.73-1.02, P=0.083)
- Landmark analysis showed significant stroke reduction after 1 year (HR 0.75, 95% CI 0.60-0.94, P=0.011)
- No increase in ischemic stroke with intensive treatment (HR 0.93, 95% CI 0.78-1.11, P=0.423)
- Benefits consistent across all subgroups including patients with previous stroke
Design
Study Type: Multicenter open-label randomized controlled trial
Randomization: 1
Blinding: Open-label with blinded outcome adjudication
Follow-up Duration: Median 3.4 years (Q1-Q3: 3.0-3.4 years)
Centers: 116
Countries: China
Sample Size: 11255
Analysis: Intention-to-treat
Inclusion Criteria
- Age ≥50 years
- SBP 130-180 mmHg
- Increased cardiovascular disease risk (established CVD or ≥2 major CV risk factors)
- Major CV risk factors: age ≥60 years (men) or ≥65 years (women), diabetes, dyslipidemia, current smoking
Exclusion Criteria
- Incident atherosclerotic cardiovascular events during past 3 months
- Scheduled revascularization within next 6 months
- Secondary cause of hypertension
- 1-minute standing SBP <110 mmHg
- Left ventricular ejection fraction <35%
- eGFR <45 mL/min per 1.73 m²
Arms
| Field | Control | Intensive treatment |
|---|---|---|
| Intervention | Target SBP <140 mmHg using unified treatment algorithms with antihypertensive medications | Target SBP <120 mmHg using unified treatment algorithms with antihypertensive medications |
| Duration | Median 3.37 years | Median 3.34 years |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Stroke (composite of ischemic and hemorrhagic) — a prespecified secondary outcome of the ESPRIT parent trial, analyzed as the primary focus of this prespecified secondary-analysis paper | Primary | 303/5,631 (5.4%) | 262/5,624 (4.7%) | 0.86 | 0.083 |
| Ischemic stroke (post hoc subtype analysis) | Secondary | 261/5,631 (4.6%) | 243/5,624 (4.3%) | HR 0.93 (95% CI 0.78-1.11) | 0.423 |
| Hemorrhagic stroke (post hoc subtype analysis) | Secondary | 45/5,631 (0.8%) | 23/5,624 (0.4%) | HR 0.51 (95% CI 0.31-0.85) | 0.009 |
| Stroke after 1 year (post hoc landmark analysis) | Secondary | 182/5,487 (3.32%) | 137/5,477 (2.50%) | HR 0.75 (95% CI 0.60-0.94) | 0.011 |
| Study intervention discontinuation | Adverse | 35/5,631 (0.6%) | 127/5,624 (2.3%) |
Subgroup Analysis
No significant interactions were found across all prespecified subgroups including age, sex, region, smoking status, alcohol consumption, BMI, baseline SBP, baseline DBP, orthostatic hypotension, diabetes, previous stroke, ASCVD, atrial fibrillation, and eGFR (all P for interaction >0.05). The treatment effect was consistent in patients with and without previous stroke.
Criticisms
- Stroke was a prespecified secondary (not primary) outcome of ESPRIT, and subtype/landmark analyses were post hoc and exploratory
- Open-label design may introduce ascertainment bias
- Overall stroke reduction did not reach statistical significance
- Limited power to detect differences between subgroups
- Study conducted entirely in China, limiting generalizability to other populations
- Prolonged antihypertensive treatment titration during COVID-19 delayed BP difference establishment
- 8 stroke events were of undetermined subtype and classified as ischemic
Funding
Funded by the China Academy of Chinese Medical Sciences Innovation Fund for Medical Science (2021-I2M-1-009); the National Key Research and Development Program (2018YFC1312400) from the Ministry of Science and Technology of China; and the Independent Project of the National Cardiovascular Disease Clinical Research Center, Fuwai Hospital, and CAMS (NCRC2021001). Free drugs were received from Changzhou Siyao Pharmaceutical, Shanghai Shyndec Pharmaceutical, Tianjin Lisheng Pharmaceutical, and Servier (Tianjin) Pharmaceutical.
Authors: Jingkuo Li, Lubi Lei, Yan Li, ..., the ESPRIT Collaborative Group
Citation: JACC. 2025;86:1405-1417
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