Landmark Trials in Hypertension Management

Population: 9,361 adults ≥50 years, SBP 130–180 mmHg, high CVD risk, no diabetes or prior stroke.

Intervention:Intensive SBP target <120 mmHg vs standard target <140 mmHg.

Result: 25% relative risk reduction in composite MACE (HR 0.75, 95% CI 0.64–0.89); 27% reduction in all-cause mortality. Trial stopped early at 3.3 years.

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.

Population: 9,361 SPRINT participants — high CVD risk adults without diabetes.

Intervention:Intensive SBP target <120 mmHg vs standard target <140 mmHg.

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.

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.

Population: 8,511 Chinese adults 60–80 years, SBP 140–190 mmHg.

Intervention: Intensive SBP target 110–130 mmHg vs standard 130–150 mmHg.

Result: 26% reduction in composite CV events (HR 0.74, 95% CI 0.60–0.92). NNT = 55 over 3.3 years to prevent one CV event.

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.

Population: 11,255 Chinese adults ≥40 years with HTN and high CVD risk.

Intervention:Intensive SBP target <120 mmHg vs standard <140 mmHg.

Result: 12% relative risk reduction in composite MACE (HR 0.88, p=0.02). Consistent with SPRINT findings in diverse Asian population.

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.

Population: 12,821 Chinese adults with type 2 diabetes and high CVD risk, SBP 130–180 mmHg.

Intervention:Intensive SBP target <120 mmHg vs standard <140 mmHg.

Result: 21% relative risk reduction in composite MACE (HR 0.79, 95% CI 0.69–0.90). Benefit consistent across subgroups.

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.

Population: 2,408 pregnant women with mild chronic HTN (SBP 140–159 or DBP 90–104 mmHg).

Intervention:Active treatment target <140/90 mmHg vs treatment reserved for severe HTN (SBP ≥160 or DBP ≥105 mmHg).

Result: 19% reduction in primary composite outcome (37.0% vs 44.2%, RR 0.82, 95% CI 0.74–0.92). No significant difference in neonatal outcomes or SGA rates.

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.

Population: 7,036 adults with acute spontaneous intracerebral hemorrhage within 6 hours.

Intervention:Intensive BP lowering bundle targeting SBP <140 mmHg within 1 hour vs guideline-based care.

Result: OR for good functional outcome 1.40 (95% CI 1.19–1.64). Significant improvement in functional recovery with intensive BP bundle.

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.

Population: 335 adults with resistant HTN on 3-drug therapy.

Intervention: Spironolactone 25–50 mg daily vs doxazosin, bisoprolol, or placebo as 4th-line agent (crossover design).

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).

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.

Population: 692 Brazilian adults with Stage 1 or 2 HTN.

Intervention: Chlorthalidone 12.5–25 mg vs hydrochlorothiazide 12.5–25 mg.

Result: Chlorthalidone achieved better 24-hour ambulatory BP control with greater SBP reduction (−3.1 mmHg more) and similar tolerability.

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.