SPRINT
(2021)Objective
To assess whether targeting a systolic blood pressure <120 mm Hg (intensive treatment) provides greater cardiovascular benefit than the standard target of <140 mm Hg in high-risk adults without diabetes or prior stroke.
Study Summary
• Increased risk of adverse events including hypotension, AKI, and electrolyte abnormalities.
• Benefits persisted during post-trial observational follow-up.
Intervention
Randomized, multicenter, open-label trial with blinded endpoint adjudication. 9361 participants aged ≥50 with increased cardiovascular risk (excluding diabetes or prior stroke) were assigned to an intensive (<120 mm Hg) or standard (<140 mm Hg) systolic BP target. Median follow-up was 3.33 years (trial period) and 3.88 years (with observational follow-up). Primary endpoint: composite of MI, acute coronary syndrome, stroke, heart failure, or CV death.
Inclusion Criteria
Age ≥50, SBP 130–180 mm Hg, and ≥1 CV risk factor (clinical/subclinical CVD, CKD with eGFR 20–59, ≥15% 10-year Framingham CV risk, or age ≥75). Excluded: diabetes, prior stroke, or dementia.
Study Design
Arms: Intensive BP Control vs. Standard BP Control
Patients per Arm: Intensive: 4678; Standard: 4683
Outcome
• All-cause mortality: 1.06% vs. 1.41%/year (HR 0.75; 95% CI 0.61–0.92; P=0.006)
• MI: HR 0.71 (95% CI 0.56–0.90; P=0.005)
• CV death: HR 0.65 (95% CI 0.46–0.90; P=0.01)
• AKI or renal failure, hypotension, electrolyte abnormalities, and syncope were significantly more frequent in the intensive group
• Renal decline (eGFR) more common in intensive group without baseline CKD
Bottom Line
Among patients at high cardiovascular risk without diabetes, targeting a systolic blood pressure of less than 120 mm Hg resulted in significantly lower rates of major adverse cardiovascular events and death from any cause compared to a target of less than 140 mm Hg. However, the intensive-treatment group experienced higher rates of certain adverse events, including hypotension, syncope, and acute kidney injury.
Major Points
- SPRINT was the most influential blood pressure trial of the decade, fundamentally changing hypertension targets worldwide. It demonstrated that treating to SBP <120 mmHg (vs <140 mmHg) reduced cardiovascular events by 27% and all-cause mortality by 25% in high-risk patients.
- 9,361 patients across 102 US centers. NIH-funded (non-industry), which enhanced credibility. Stopped early by DSMB after median 3.33 years due to overwhelming benefit — later confirmed in post-trial follow-up to 3.88 years.
- Primary composite (MI, ACS, stroke, HF, CV death): 1.77%/yr intensive vs 2.40%/yr standard (HR 0.73, 95% CI 0.63–0.86, p<0.001). NNT = 61 over 3.3 years to prevent one primary event.
- All-cause mortality significantly reduced: 1.06% vs 1.41%/yr (HR 0.75, 95% CI 0.61–0.92, p=0.006) — one of the rare trials to show mortality benefit from BP lowering, making it a game-changer for treatment targets.
- Heart failure was the most robustly reduced component: HR 0.62 (95% CI 0.45–0.84, p=0.002) — 38% reduction. This spawned the SPRINT-HF hypothesis about BP's role in HFpEF prevention.
- Stroke itself was NOT significantly reduced: HR 0.89 (95% CI 0.63–1.25, p=0.50) — surprising and important. Stroke represented only ~12% of primary events. Prior stroke patients were excluded, so this trial doesn't inform secondary stroke prevention.
- Critical caveat: BP was measured using automated UNATTENDED oscillometric readings (AOBP) — these read ~10–15 mmHg lower than typical clinic BPs. The intensive target of <120 mmHg by AOBP roughly corresponds to <130–135 mmHg by conventional clinic measurement. This distinction is crucial for clinical implementation.
- Adverse events significantly higher with intensive treatment: hypotension (2.8% vs 1.7%), syncope (3.3% vs 2.3%), AKI (4.7% vs 2.6%), electrolyte abnormalities (5.3% vs 3.8%) — the NNH for AKI was ~48, comparable to the NNT of ~61.
- SPRINT-MIND substudy showed intensive BP lowering significantly reduced mild cognitive impairment (HR 0.81, p=0.01) and a trend toward reduced probable dementia — the first large randomized evidence linking BP control to cognitive protection.
- Directly influenced 2017 ACC/AHA guidelines that lowered the hypertension threshold to 130/80 mmHg (from 140/90) and set treatment targets at <130/80 for most adults — the most consequential guideline change in hypertension in 30 years.
Study Design
- Study Type
- Randomized clinical trial.
- Randomization
- Yes
- Blinding
- Open-label for blood pressure targets, but outcome adjudication was blinded.
- Sample Size
- 9361
- Follow-up
- Median of 3.33 years of intervention, with post-trial follow-up to 3.88 years.
- Centers
- 102
- Countries
- United States
Primary Outcome
Definition: A composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes.
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 2.40% per year | 1.77% per year | 0.73 (0.63 to 0.86) | <0.001 |
Limitations & Criticisms
- Stopped early (median 3.33 years) — early stopping can overestimate treatment effects (Pocock bias). However, post-trial follow-up to 3.88 years confirmed persistent benefit, mitigating this concern.
- UNATTENDED automated BP measurement (AOBP) — the ~10–15 mmHg lower readings vs conventional clinic BPs mean that SPRINT's <120 target ≈ <130–135 in routine clinical practice. Many clinicians over-aggressively treat to clinic BP <120, causing iatrogenic hypotension.
- Excluded BOTH diabetes and prior stroke — the two largest populations needing BP guidance. ACCORD-BP (diabetes, negative) and SPS3 (stroke, positive for ICH reduction) addressed these populations separately, but SPRINT's results cannot be directly extrapolated.
- Higher AKI rate (4.7% vs 2.6%) with intensive treatment — while most was reversible, long-term renal consequences of aggressive BP lowering remain uncertain. The post-trial follow-up showed stable eGFR in both groups.
- US-only trial — limits generalizability to other healthcare systems where monthly medication titration visits may not be feasible. Resource-limited settings may struggle to implement SPRINT-level management.
- Open-label BP targets — physicians and patients knew the target, potentially influencing non-BP management (more clinic visits, more monitoring, more attention in the intensive arm = Hawthorne effect).
- Stroke was NOT significantly reduced (HR 0.89, p=0.50) — despite being a component of the primary endpoint. This non-finding is important: SPRINT does not support intensive BP for stroke prevention specifically.
- Mean BP achieved was 121 mmHg (intensive) vs 136 mmHg (standard) — the actual difference was ~15 mmHg, not the 20 mmHg target difference. Imperfect adherence to targets is realistic but dilutes the estimated treatment effect.
- Polypharmacy: intensive group averaged 2.8 medications vs 1.8 in standard — the additional medication burden, cost, side effects, and adherence challenges are clinically significant, especially in elderly patients.
Citation
N Engl J Med 2021;384:1921-1930.