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?
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) | Primary | 303/5,631 (5.4%) | 262/5,624 (4.7%) | 0.86 | 0.083 |
| Ischemic stroke | Effect Size: 0.93; 95% CI: 0.78-1.11 | Secondary | 261/5,631 (4.6%) | 243/5,624 (4.3%) | 0.423 | |
| Hemorrhagic stroke | Effect Size: 0.51; 95% CI: 0.31-0.85 | Secondary | 45/5,631 (0.8%) | 23/5,624 (0.4%) | 0.009 | |
| Stroke after 1 year (landmark analysis) | Effect Size: 0.75; 95% CI: 0.60-0.94 | Secondary | 182/5,487 (3.32%) | 137/5,477 (2.50%) | 0.011 | |
| Study intervention discontinuation | Adverse | 35 (0.6%) | 127 (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
- 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
China Academy of Chinese Medical Sciences Innovation Fund for Medical Science (2021-I2M-1-009), National Key Research and Development Program (2018YFC1312400), Independent Project of National Cardiovascular Disease Clinical Research Center
Authors: Jingkuo Li, Lubi Lei, Yan Li, ..., the ESPRIT Collaborative Group
Citation: JACC. 2025;86:1405-1417
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