Landmark Trials in Hypertension Management
Key randomized controlled trials that shaped the 2025 AHA/ACC Guideline for the Diagnosis and Management of Hypertension. Presented with population, intervention, primary outcome, and clinical significance.
SPRINT
High impactn = 9,3612015Systolic Blood Pressure Intervention Trial
Population
Adults ≥50 years, SBP 130–180, high CVD risk, no diabetes or prior stroke
Intervention
Intensive SBP target <120 mmHg
Comparator
Standard SBP target <140 mmHg
Primary Outcome
Composite MACE
Result
25% relative risk reduction in MACE (HR 0.75, 95% CI 0.64–0.89); 27% reduction in all-cause mortality. Trial stopped early at 3.3 years.
Clinical Significance
Landmark evidence for intensive BP lowering. Directly informed the 2025 AHA/ACC guideline's recommendation of SBP <120 mmHg for high-risk patients when tolerated.
SPRINT Research Group. N Engl J Med. 2015;373(22):2103-2116.
View paper →SPRINT-MIND
High impactn = 9,3612019SPRINT Memory and Cognition IN Decreased Hypertension
Population
SPRINT participants — high CVD risk adults without diabetes
Intervention
Intensive SBP target <120 mmHg
Comparator
Standard SBP target <140 mmHg
Primary Outcome
Probable dementia
Result
17% non-significant reduction in probable dementia (HR 0.83, 95% CI 0.67–1.04); 19% significant reduction in mild cognitive impairment (p=0.01). White matter lesion volume reduced.
Clinical Significance
First large RCT demonstrating cognitive benefit from intensive BP control. Supports treating HTN as a modifiable risk factor for dementia.
SPRINT MIND Investigators. JAMA. 2019;321(6):553-561.
View paper →STEP
High impactn = 8,5112021Strategy of Blood Pressure Intervention in Elderly Hypertensive Patients
Population
Chinese adults 60–80 years, SBP 140–190 mmHg
Intervention
Intensive SBP target 110–130 mmHg
Comparator
Standard SBP target 130–150 mmHg
Primary Outcome
Composite CV events
Result
26% reduction in CV events (HR 0.74, 95% CI 0.60–0.92). NNT = 55 over 3.3 years to prevent one CV event.
Clinical Significance
First large RCT of intensive BP control in older adults. Demonstrated safety and benefit in the 60–80 age group, supporting intensive treatment in appropriately selected elderly patients.
Zhang W, et al. N Engl J Med. 2021;385(14):1268-1279.
View paper →ESPRIT
High impactn = 11,2552023Effective Systolic Pressure Reduction in Chinese Adults with Hypertension Trial
Population
Chinese adults ≥40 years with HTN, high CVD risk
Intervention
Intensive SBP target <120 mmHg
Comparator
Standard SBP target <140 mmHg
Primary Outcome
Composite CV events
Result
12% relative risk reduction in MACE (HR 0.88, p=0.02). Consistent with SPRINT findings in diverse Asian population.
Clinical Significance
Confirmed generalizability of intensive BP targets beyond Western populations. Supports <120 mmHg target in high-risk Asian patients.
The ESPRIT Investigators. Lancet. 2023;402(10409):1228-1238.
View paper →BPROAD
High impactn = 12,8212024Blood Pressure control targets in type 2 diabetic patients with high CVD Risk
Population
Chinese adults with type 2 diabetes and high CVD risk, SBP 130–180 mmHg
Intervention
Intensive SBP target <120 mmHg
Comparator
Standard SBP target <140 mmHg
Primary Outcome
Composite MACE
Result
21% relative risk reduction in MACE (HR 0.79, 95% CI 0.69–0.90). Benefit consistent across subgroups.
Clinical Significance
First large RCT of intensive BP control specifically in T2DM patients. Resolved uncertainty about intensive targets in diabetes — intensive control beneficial.
BPROAD Research Group. N Engl J Med. 2024;390(3):215-226.
View paper →CHAP
High impactn = 2,4082022Chronic Hypertension and Pregnancy Trial
Population
Pregnant women with mild chronic HTN (SBP 140–159 or DBP 90–104 mmHg)
Intervention
Active treatment target <140/90 mmHg
Comparator
Treatment reserved for severe HTN (SBP ≥160 or DBP ≥105 mmHg)
Primary Outcome
Composite adverse pregnancy outcome (preeclampsia with severe features, preterm birth, placental abruption, fetal/neonatal death)
Result
19% reduction in primary outcome (37.0% vs 44.2%, RR 0.82, 95% CI 0.74–0.92). No significant difference in neonatal outcomes or SGA rates.
Clinical Significance
Changed practice for chronic HTN in pregnancy. Guideline now recommends treatment to <140/90 during pregnancy, overturning previous hesitancy about treating mild HTN in pregnancy.
Tita AT, et al. N Engl J Med. 2022;386(19):1780-1792.
View paper →INTERACT3
Moderate impactn = 7,0362023Third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial
Population
Adults with acute spontaneous intracerebral hemorrhage within 6 hours
Intervention
Intensive BP lowering bundle targeting SBP <140 mmHg within 1 hour
Comparator
Guideline-based care
Primary Outcome
Functional recovery (modified Rankin Scale) at 6 months
Result
OR for good functional outcome 1.40 (95% CI 1.19–1.64). Significant improvement in functional recovery with intensive BP bundle.
Clinical Significance
Supports aggressive BP reduction in acute ICH. Informs the guideline's recommendation for target SBP <140 mmHg in hypertensive ICH.
Anderson CS, et al. Lancet. 2023;402(10395):27-40.
View paper →PATHWAY-2
High impactn = 3352015Prevention And Treatment of Hypertension With Algorithm-based therapY 2
Population
Adults with resistant HTN on 3-drug therapy
Intervention
Spironolactone 25–50 mg daily as 4th-line agent
Comparator
Doxazosin, bisoprolol, or placebo as 4th-line agent (crossover design)
Primary Outcome
Home systolic BP at 12 weeks
Result
Spironolactone reduced home SBP by 8.70 mmHg more than placebo (p<0.0001). Superior to doxazosin (−4.03 mmHg) and bisoprolol (−4.48 mmHg).
Clinical Significance
Established spironolactone as the preferred 4th-line agent for resistant HTN. Reinforced role of mineralocorticoid receptor antagonism in volume-mediated resistant HTN.
Williams B, et al. Lancet. 2015;386(10008):2059-2068.
View paper →PREVER-Treatment
Moderate impactn = 6922016Prevention of Cardiovascular Events in Patients with Previous Cardiovascular Disease or High Cardiovascular Risk: Treatment Study
Population
Brazilian adults with Stage 1 or 2 HTN
Intervention
Chlorthalidone 12.5–25 mg vs hydrochlorothiazide 12.5–25 mg
Comparator
Hydrochlorothiazide
Primary Outcome
BP control at 18 months
Result
Chlorthalidone achieved better 24-hour ambulatory BP control. Chlorthalidone showed greater reduction in SBP (−3.1 mmHg more) with similar tolerability.
Clinical Significance
Supports the 2025 guideline preference for chlorthalidone or indapamide over hydrochlorothiazide as the preferred thiazide-type diuretic for HTN treatment.
Mosso LM, et al. J Hypertens. 2016;34(7):1323-1332.
View paper →Trial summaries are provided for educational purposes. Effect sizes are approximate; consult primary publications for complete data. Source: 2025 AHA/ACC Guideline for the Diagnosis and Management of Hypertension in Adults. Whelton PK, et al. Hypertension. 2025. doi:10.1161/HYP.0000000000000116