Targeting systolic BP <120 mm Hg in high-risk adults without diabetes reduced major cardiovascular events and all-cause mortality versus <140 mm Hg, but increased hypotension, syncope, electrolyte abnormalities, and acute kidney injury; injurious falls were not increased.

Background

Hypertension is common and a leading global risk factor for death and disability. While lowering blood pressure reduces cardiovascular risk, the optimal systolic target for adults without diabetes has been uncertain. Prior trials largely established benefits down to <150 mm Hg, with limited evidence for lower targets. SPRINT tested whether a target <120 mm Hg would improve outcomes compared with the commonly used target <140 mm Hg.

Patients

• N = 9361 adults, age ≥50 years, systolic BP ≥130 mm Hg, increased cardiovascular risk.
• Increased risk criteria: clinical or subclinical CVD (excluding stroke), chronic kidney disease (eGFR 20–<60 ml/min/1.73 m²), Framingham 10-year CVD risk ≥15%, or age ≥75 years.
• Key exclusions: diabetes mellitus, prior stroke, polycystic kidney disease.
• Baseline characteristics: mean age 67.9 years; 28% ≥75 years; 36% female; 31% Black; 28% with CKD; 20% with CVD; mean SBP ~140 mm Hg, DBP ~78 mm Hg.

Intervention

Intensive blood-pressure management targeting systolic BP <120 mm Hg using guideline-supported medication algorithms, lifestyle counseling, and frequent visits (monthly initially, then every 3 months). Medications were provided at no cost; mean number of antihypertensives during follow-up: 2.8.

Control

Standard management targeting systolic BP <140 mm Hg (dose reductions if SBP <130 once or <135 twice). Mean number of antihypertensives during follow-up: 1.8.

Outcome

• Primary outcome: Composite of myocardial infarction, other acute coronary syndrome, stroke, acute decompensated heart failure, or death from cardiovascular causes.
• Key secondary outcomes: Individual components of the primary outcome, death from any cause, composite of primary outcome or death, prespecified renal outcomes (definitions differed by baseline CKD status), and safety events (hypotension, syncope, bradycardia, electrolyte abnormalities, acute kidney injury/renal failure, injurious falls).

Study Design

• Multicenter, randomized, controlled, open-label trial with blinded outcome adjudication (PROBE design) at 102 U.S. sites (including Puerto Rico).
• Randomization stratified by site; automated office BP measurements after 5 minutes rest.
• Intention-to-treat analyses; independent data and safety monitoring board.
• Stopped early for benefit after median 3.26 years (planned average up to 5 years).

Level of Evidence

Level I (randomized controlled trial).

Follow up period

Median 3.26 years.

Results

Blood pressure separation

• At 1 year: mean SBP 121.4 vs 136.2 mm Hg (intensive vs standard).
• Mean SBP during follow-up: 121.5 vs 134.6 mm Hg.

Primary outcome

• Events: 243/4678 (5.2%) vs 319/4683 (6.8%); hazard ratio (HR) 0.75 (95% CI, 0.64–0.89).
• Number needed to treat (NNT) over 3.26 years ≈ 61.

Secondary outcomes

• All-cause mortality: 155 (3.3%) vs 210 (4.5%); HR 0.73 (95% CI, 0.60–0.90); NNT ≈ 90.
• Death from cardiovascular causes: 37 (0.8%) vs 65 (1.4%); HR 0.57 (95% CI, 0.38–0.85); NNT ≈ 172.
• Heart failure: 62 (1.3%) vs 100 (2.1%); HR 0.62 (95% CI, 0.45–0.84); NNT ≈ 125.
• Myocardial infarction: 97 (2.1%) vs 116 (2.5%); HR 0.83 (95% CI, 0.64–1.09).
• Stroke: 62 (1.3%) vs 70 (1.5%); HR 0.89 (95% CI, 0.63–1.25).
• Composite (primary outcome or death): 332 (7.1%) vs 423 (9.0%); HR 0.78 (95% CI, 0.67–0.90).

Renal outcomes

• Baseline CKD: Composite of ≥50% eGFR decline or ESRD similar between groups; HR 0.89 (95% CI, 0.42–1.87).
• No baseline CKD: ≥30% eGFR decline to <60 ml/min/1.73 m² was more frequent with intensive therapy: 3.8% vs 1.1%; HR 3.49 (95% CI, 2.44–5.10).

Serious adverse events (selected)

• Hypotension (ED visit/SAE): 3.4% vs 2.0%; HR 1.70 (95% CI, 1.31–2.22).
• Syncope (ED visit/SAE): 3.5% vs 2.4%; HR 1.44 (95% CI, 1.13–1.83).
• Electrolyte abnormality (ED visit/SAE): 3.8% vs 2.8%; HR 1.38 (95% CI, 1.10–1.72).
• Acute kidney injury/acute renal failure (ED visit/SAE): 4.4% vs 2.6%; HR 1.71 (95% CI, 1.40–2.10).
• Injurious falls (ED visit/SAE): 7.1% vs 7.1%; HR 1.00 (95% CI, 0.86–1.17).

Limitations

• Open-label design; potential ascertainment bias despite blinded outcome adjudication.
• Stopped early for benefit, which can overestimate effect sizes and limit long-term safety assessment.
• Excluded key populations (diabetes, prior stroke, age <50, many very frail/nursing home residents); generalizability may be limited.
• Automated office BP methods may differ from routine clinical measurements.
• Renal and central nervous system outcomes require longer follow-up to fully characterize risks/benefits.

Funding

Funded by the U.S. National Institutes of Health: primarily the National Heart, Lung, and Blood Institute, with co-sponsorship from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the National Institute on Aging. Additional support from NIH Clinical and Translational Science Awards and the U.S. Department of Veterans Affairs. Azilsartan and azilsartan/chlorthalidone were donated by Takeda Pharmaceuticals International and Arbor Pharmaceuticals; donors had no other study role.

Citation

SPRINT Research Group. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. New England Journal of Medicine. 2015;373:2103–2116. Published online November 9, 2015; updated September 1, 2017. DOI: 10.1056/NEJMoa1511939. ClinicalTrials.gov: NCT01206062.