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This trial aims to assess, in patients aged ≥50 years with an average baseline SBP ≥130 mmHg and a previous history of cardiovascular diseases or at high vascular risk, the effects on the incidence of major cardiovascular events during the scheduled treatment period of greater reduction in blood pressure with a SBP target <120 mmHg versus <140 mmHg.
This study is a multicenter, open-label, randomized controlled trial, which will randomize participants aged ≥50 years with an average baseline SBP ≥130 mmHg and a previous history of cardiovascular diseases or at high vascular risk. The study will compare the effects on the incidence of major cardiovascular events of allocation to achieve an intensive SBP goal (SBP <120 mmHg) with a standard SBP goal (SBP <140 mmHg) in four years of follow up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intensive treatment group | Experimental | Participants randomized into the Intensive treatment group will have a goal of SBP <120 mmHg. A two- or three-drug regimen should be initiated at randomization for most participants. Drug doses should be increased and/or additional antihypertensive medications should be added at each visit in the intensive treatment group, usually at monthly intervals, until the participant's goal of <120 mmHg has been reached or the local investigator decides no further antihypertensive medications may be added. |
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| Standard treatment group | Active Comparator | Participants randomized into the Standard treatment group will have a goal of SBP <140 mmHg. It is expected to achieve a SBP of 135-139 mmHg in as many participants as possible. Medication dose titration or addition of another drug is indicated if SBP is ≥160 mmHg at a single visit or is ≥140 mmHg at two consecutive visits. Down titration should be carried out if the SBP is <130 mmHg at a single visit or <135 mmHg at two consecutive visits. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Intensive BP treatment group | Drug | Participants in the Intensive BP treatment group have a goal of SBP <120 mmHg. It is recommended to provide long-acting antihypertensive medications, that is once daily, unless other medication delivery frequency is needed. The local investigator may select among the available study antihypertensive medications. Other drugs not supplied by the trial may also be used as the investigator determines appropriate. One or more medications from the following classes of agents will be provided by the study for use in managing participants in both randomization groups to achieve study goals: Angiotension converting enzyme (ACE)-inhibitors; Angiotension receptor blockers (ARBs); Thiazide-type diuretics; Loop diuretics; Potassium-sparing diuretics; Beta-blockers; Calcium channel blockers (CCBs); Direct vasodilators; Alpha1-receptor blockers; Sympatholytics |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with composite of major CVD events | Composite outcome of myocardial infarction, coronary or non-coronary revascularization, chronic or acute decompensated heart failure hospitalization or emergency department visit, stroke, or death from cardiovascular disease | 4 years |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with myocardial infarction | 4 years | |
| Number of participants with coronary revascularization | 4 years | |
| Number of participants with non-coronary revascularization |
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Inclusion Criteria:
At least ≥50 years old, and
Systolic blood pressure (SBP): (having documentation of SBP to meet the criteria below on 2 consecutive visits)
Prior vascular disease or at high vascular risk
Previous myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), at least a 50% diameter stenosis of a coronary, chest pain with objective evidence of myocardial ischemia (load electrocardiogram or load image examination indicated myocardial ischemia)
Previous stroke
Carotid endarterectomy (CE), or carotid stenting
Peripheral artery disease (PAD) with revascularization
Abdominal aortic aneurysm (AAA) ≥5 cm with repair
Combine with no less than two risk factors below
Exclusion Criteria:
Known secondary cause of hypertension
An indication for a specific BP lowering medication that the participant is not taking and the participant has not been documented to be intolerant of the medication class
One minute standing SBP <110 mmHg (not applicable if unable to stand)
Arm circumference too large or small to allow accurate blood pressure measurement with available devices
Proteinuria defined as urine dipstick ≥2+ protein at screening
Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy
eGFR <45 ml/min /1.73m2 or end-stage renal disease (ESRD)
Previous MI, stroke, or hospitalization for angina, PCI, CABG, CE or carotid stenting, PAD with revascularization, AAA≥5 cm with repair within last 3 months
Symptomatic heart failure within the past 6 months or documented left ventricular ejection fraction (by any method) <35%
PCI or CABG planned for the next 6 months
A medical condition likely to limit survival to less than 3 years, or a cancer (other than non-melanoma skin cancer) diagnosed and treated within the past two years that, in the judgment of local clinical investigators, would compromise a participant's ability to comply with the protocol and complete the trial
Any organ transplant
Pregnancy, breast-feeding, or of child-bearing potential and not using adequate contraception
Any factors judged by local clinic investigators to be likely to limit adherence to interventions. For example,
Currently participation in a clinical trial with an unlicensed drug or device
Living in the same household as an already randomized participant
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| Name | Affiliation | Role |
|---|---|---|
| Jing Li, MD, PhD | National Center for Cardiovascular Diseases | Principal Investigator |
| Jiamin Liu, MD | National Center for Cardiovascular Diseases | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fuwai Hospital, Chinese Academy of Medical Sciences | Beijing | 100087 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41920135 | Derived | Peng Y, Li Y, Li S, Zhang L, Zhao L, Liu J, Yan X, Liu J, Chai Z, Liang X, Tian C, Huo F, Wu L, Chen X, Che H, Zhang M, Duan R, Wang H, Liu X, Li Z, Liu Z, Wu L, Zhou W, Zhang H, Li J. Achieving Intensive Blood Pressure Control in High-Risk Patients: Implementation Insights From the ESPRIT Trial. J Am Coll Cardiol. 2026 May 12;87(18):2450-2470. doi: 10.1016/j.jacc.2026.01.083. Epub 2026 Apr 1. | |
| 41744069 |
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| ID | Term |
|---|---|
| D006973 | Hypertension |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| Standard BP treatment group | Drug | Participants in the Standard BP treatment group have a goal of SBP <140 mmHg. The same medications used in the Intensive BP treatment group will be used for the Standard BP treatment group. |
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| 4 years |
| Number of participants with chronic or acute decompensated heart failure hospitalization or emergency department visit | 4 years |
| Number of participants with stroke | 4 years |
| Number of participants with cardiovascular death | 4 years |
| Number of participants with all-cause death | 4 years |
| Number of participants with composite outcome of the primary composite with all-cause death | 4 years |
| Number of participants with end-stage kidney disease (ESKD), a sustained decline in eGFR to <10 mL/min/1.73m2, renal death, or a sustained decline of ≥40% in eGFR from randomization | 4 years |
| Number of participants with all-cause dementia or mild cognitive impairment | 4 years |
| Difference of arteriole-to-venule ratio measured by fundus photography between intensive treatment group and standard treatment group | at 4-year final follow-up visit |
| Derived |
| Wang B, Sun Y, Li Y, Wu L, Peng Y, Li S, Ge J, Zhang L, Zhao L, Liu J, Su S, Zhang B, Liu Y, Ma X, Zuo Z, Zhang H, Wang Y, Liu J, Li J. Intensive BP Control and Cognitive Function: A Randomized Clinical Trial. Hypertension. 2026 Apr;83(4):e26572. doi: 10.1161/HYPERTENSIONAHA.125.26572. Epub 2026 Feb 26. |
| 41105075 | Derived | Huang X, Zhang H, Li Y, Ge J, Sun Y, Zhang L, Zhao L, Liu J, Zhang C, Du J, Li Y, Zhang H, Hao F, Wang Q, Xu W, Liu J, Li J. Modest Effects of Intensive Blood Pressure-Lowering on Quality of Life in Patients at High Cardiovascular Risk: The ESPRIT Trial. J Am Coll Cardiol. 2025 Oct 28;86(17):1392-1401. doi: 10.1016/j.jacc.2025.06.010. Epub 2025 Oct 17. |
| 41105073 | Derived | Wang B, Shi D, Zhang Z, Zhang L, Sun Y, Liu J, Yan X, Jing J, Li J, Song J, Li Y, Li G, Zhang L, Wang Z, Chen J, Zhang W, Cai S, Han S, Luan T, Yi S, Su S, Du J, Kou X, Liu J, Dai X, Li N, Zhu J, Tang C, Liu S, Su H, Liu Y, Mao Y, Yang X, He M, Zhang Q, Li J. Effect of Intensive Blood Pressure Lowering Treatment on Retinal Microvasculature: Secondary Analysis From ESPRIT. J Am Coll Cardiol. 2025 Oct 28;86(17):1377-1388. doi: 10.1016/j.jacc.2025.05.020. Epub 2025 Oct 17. |
| 41091084 | Derived | Li S, Peng Y, Li Y, Sun Y, Yan X, Zhang L, Liu J, Zhao L, Liu J, Qian J, Zhai N, Dong L, Ruan J, Zhang P, Wei X, Liu Y, Ma Q, Huang W, Zhang Q, An C, Liu J, Sheng L, Zhang H, Li J; ESPRIT Investigators. Effects of Intensive Blood Pressure Control in Patients With Frailty: A Post Hoc Analysis From ESPRIT. J Am Coll Cardiol. 2026 Jan 6;87(1):4-16. doi: 10.1016/j.jacc.2025.08.092. Epub 2025 Oct 15. |
| 38945140 | Derived | Liu J, Li Y, Ge J, Yan X, Zhang H, Zheng X, Lu J, Li X, Gao Y, Lei L, Liu J, Li J; ESPRIT Collaborative Group. Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial. Lancet. 2024 Jul 20;404(10449):245-255. doi: 10.1016/S0140-6736(24)01028-6. Epub 2024 Jun 27. |
| 36398903 | Derived | Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2022 Nov 18;11(11):CD010315. doi: 10.1002/14651858.CD010315.pub5. |
| 32905623 | Derived | Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2020 Sep 9;9(9):CD010315. doi: 10.1002/14651858.CD010315.pub4. |