Neurology Clinical Trial Database
SPRINT
Final Report of a Trial of Intensive versus Standard Blood-Pressure Control
Clinical Question
In patients at increased cardiovascular risk without diabetes or prior stroke, does intensive systolic blood pressure control (target <120 mm Hg) result in lower rates of major adverse cardiovascular events and all-cause mortality compared to standard control (target <140 mm Hg)?
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.
Design
Study Type: Randomized clinical trial.
Randomization: 1
Blinding: Open-label for blood pressure targets, but outcome adjudication was blinded.
Enrollment Period: November 2010 through March 2013.
Follow-up Duration: Median of 3.33 years of intervention, with post-trial follow-up to 3.88 years.
Centers: 102
Countries: United States
Sample Size: 9361
Analysis: Intention-to-treat.
Inclusion Criteria
- Age ≥50 years (no upper age limit — 28% were ≥75 years, enabling the SPRINT-SENIOR substudy).
- Systolic blood pressure 130–180 mmHg (on 0–4 antihypertensive medications). Patients already on BP meds were eligible if SBP was within this range.
- At least one additional indicator of increased cardiovascular risk: (a) clinical or subclinical cardiovascular disease (excluding stroke), (b) chronic kidney disease with eGFR 20–59 mL/min/1.73m² (28% of cohort), (c) 10-year Framingham CVD risk score ≥15%, or (d) age ≥75 years.
- Willing and able to comply with intensive BP management protocol including monthly visits for dose titration.
Exclusion Criteria
- Diabetes mellitus — excluded because the concurrent ACCORD-BP trial was testing similar targets in diabetics (and found no benefit at <120 mmHg in DM).
- Previous stroke — a critical exclusion for neurologists. SPRINT cannot be used to guide secondary stroke prevention BP targets. SPS3 addressed this population.
- Dementia or inability to give informed consent — though the SPRINT-MIND substudy assessed cognitive outcomes in enrolled patients.
- Heart failure with reduced ejection fraction (NYHA Class III–IV) or LVEF <35% — these patients had different BP physiology and were excluded.
- Expected survival <3 years from non-cardiovascular cause.
- Proteinuria >1 g/day (nephrotic range) — renal disease this severe has different BP management considerations.
- Polycystic kidney disease — different pathophysiology and BP targets.
- Resident of nursing home — to ensure independence for compliance with intensive management.
- eGFR <20 mL/min/1.73m² or dialysis — severe CKD excluded.
- Pregnancy or planned pregnancy — different BP targets apply.
Arms
| Field | Control | Intensive Treatment |
|---|---|---|
| Intervention | A systolic blood-pressure target of less than 140 mm Hg. | A systolic blood-pressure target of less than 120 mm Hg. |
| Duration | Median of 3.33 years | Median of 3.33 years |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| A composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. | Primary | 2.40% per year | 1.77% per year | 0.73 | <0.001 |
| All-cause mortality | Secondary | 1.41% per year | 1.06% per year | HR 0.75 (95% CI, 0.61 to 0.92) | 0.006 |
| Heart failure | Secondary | 1.44% per year | 0.94% per year | HR 0.68 (95% CI, 0.50 to 0.92) | 0.01 |
| Death from cardiovascular causes | Secondary | 0.65% per year | 0.43% per year | HR 0.66 (95% CI, 0.45 to 0.98) | 0.04 |
| Hypotension | Adverse | 1.7% | 2.8% | HR 1.67 (95% CI, 1.34-2.07) | <0.001 |
| Syncope | Adverse | 2.3% | 3.3% | HR 1.33 (95% CI, 1.10-1.61) | 0.003 |
| Electrolyte abnormalities | Adverse | 3.8% | 5.3% | HR 1.35 (95% CI, 1.15-1.58) | <0.001 |
| Acute kidney injury or failure | Adverse | 2.6% | 4.7% | HR 1.80 (95% CI, 1.48-2.20) | <0.001 |
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.
Funding
National Institutes of Health (NHLBI, NIDDK, NIA, NINDS).
Based on: SPRINT (The New England Journal of Medicine, 2021)
Authors: The SPRINT Research Group
Citation: N Engl J Med 2021;384:1921-1930.
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