Neurology Clinical Trial Database
BPROAD
Intensive Blood-Pressure Control in Patients with Type 2 Diabetes
Clinical Question
Does intensive systolic blood pressure control (<120 mm Hg) reduce cardiovascular events in patients with type 2 diabetes compared to standard control (<140 mm Hg)?
Bottom Line
Intensive systolic blood pressure control (<120 mm Hg) significantly reduced major cardiovascular events in patients with type 2 diabetes, without increasing overall serious adverse events, though symptomatic hypotension and hyperkalemia were more frequent.
Major Points
- BPROAD is the largest RCT specifically testing intensive BP control (<120 mmHg) in type 2 diabetes — 12,821 patients, median 4.2 years follow-up. Published NEJM 2025.
- Primary outcome (composite of nonfatal stroke, nonfatal MI, treatment or hospitalization for HF, or CV death): HR 0.79 (95% CI 0.69–0.90, p<0.001) — a 21% relative risk reduction with intensive control.
- Fatal or nonfatal stroke was individually reduced (HR 0.79, 95% CI 0.67–0.92) — making BPROAD directly relevant to stroke prevention in diabetic patients.
- Critically, BPROAD confirms and extends SPRINT findings to diabetic patients — SPRINT explicitly EXCLUDED diabetes, leaving a major evidence gap that BPROAD fills.
- Achieved BP separation: mean SBP 121.6 mmHg (intensive) vs 133.2 mmHg (standard) — a ~12 mmHg difference, similar to SPRINT's ~13 mmHg separation.
- Only ~60% of intensive-group patients achieved target SBP <120 mmHg — yet still showed significant benefit, suggesting even partial achievement of intensive targets is meaningful.
- No increase in serious adverse events overall (36.5% vs 36.3%, HR 1.00, P=0.96). However, symptomatic hypotension (0.1% vs <0.1%, HR 7.92, P=0.05) and serum potassium >5.5 mmol/L (2.8% vs 2.0%, HR 1.41, P=0.003) were more frequent with intensive control.
- No mortality benefit (all-cause mortality HR 0.95, not significant) — similar to SPRINT, where CV mortality was reduced but all-cause mortality was borderline.
- Conducted entirely in China — raises questions about generalizability to non-Asian populations with different dietary patterns, body composition, and CV risk profiles.
- Resolves the ACCORD BP controversy — ACCORD (2010) found no benefit of intensive BP control in diabetes but was underpowered (4,733 patients, factorial design with glycemic intervention). BPROAD with 2.7× the sample size definitively shows benefit.
Design
Study Type: Randomized, open-label, blinded-endpoint trial
Randomization: 1
Blinding: Open-label with blinded adjudication of outcomes
Enrollment Period: February 2019 to December 2021
Follow-up Duration: Median 4.2 years
Centers: 145
Countries: China
Sample Size: 12821
Analysis: Intention-to-treat using Cox proportional-hazards regression; multiple imputation for missing outcome data (assuming data missing at random); Fine and Gray hazard model used for competing risk sensitivity
Inclusion Criteria
- Type 2 diabetes
- Age ≥50 years
- Elevated systolic BP: 130 to 180 mm Hg if on antihypertensive medications, or ≥140 mm Hg if not on antihypertensive therapy
- Increased cardiovascular risk defined as ≥1 of: history of clinical CVD ≥3 months before enrollment; subclinical CVD within 3 years before enrollment; ≥2 cardiovascular risk factors; or CKD with eGFR 30 to <60 mL/min/1.73 m²
Exclusion Criteria
- Detailed exclusion criteria are not enumerated in the primary article; see Supplementary Appendix Section S2 for the full list.
Arms
| Field | Intensive Treatment | Control |
|---|---|---|
| Intervention | Antihypertensive therapy targeting systolic BP <120 mm Hg | Antihypertensive therapy targeting systolic BP <140 mm Hg |
| Duration | Median 4.2 years | Median 4.2 years |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Composite of first occurrence of nonfatal stroke, nonfatal myocardial infarction, treatment or hospitalization for heart failure, or death from cardiovascular causes | Primary | 492 events; 2.09 per 100 person-years | 393 events; 1.65 per 100 person-years | 0.79 | <0.001 |
| Fatal or nonfatal myocardial infarction | Secondary | 81 events; 0.33 per 100 person-yr | 68 events; 0.28 per 100 person-yr | 0.84 (0.60–1.16) | |
| Fatal or nonfatal stroke | Secondary | 356 events; 1.50 per 100 person-yr | 284 events; 1.19 per 100 person-yr | 0.79 (0.67–0.92) | |
| Treatment or hospitalization for heart failure | Secondary | 46 events; 0.19 per 100 person-yr | 31 events; 0.13 per 100 person-yr | 0.66 (0.41–1.04) | |
| Death from cardiovascular causes | Secondary | 79 events; 0.32 per 100 person-yr | 60 events; 0.24 per 100 person-yr | 0.76 (0.55–1.06) | |
| Death from any cause | Secondary | 179 events; 0.73 per 100 person-yr | 169 events; 0.69 per 100 person-yr | 0.95 (0.77–1.17) | |
| Expanded composite: primary-outcome event or death from any cause | Secondary | 584 events; 2.48 per 100 person-yr | 493 events; 2.07 per 100 person-yr | 0.83 (0.74–0.94) | |
| CKD progression (composite of ESRD, eGFR <15, or >50% eGFR decrease in patients with baseline CKD) | Secondary | 16 events; 1.11 per 100 person-yr | 24 events; 1.61 per 100 person-yr | 1.36 (0.71–2.59) | |
| CKD development (eGFR <60 and >30% decrease in patients without baseline CKD) | Secondary | 214 events; 1.05 per 100 person-yr | 232 events; 1.14 per 100 person-yr | 1.11 (0.92–1.34) | |
| Incident albuminuria (doubling of UACR to ≥10) | Secondary | 648 events; 13.84 per 100 person-yr | 554 events; 11.29 per 100 person-yr | 0.87 (0.77–0.97) | |
| Serious adverse events | Adverse | 2328/6407 (36.3%) | 2340/6414 (36.5%) | 1.00 (0.94–1.06) | 0.96 |
| Symptomatic hypotension | Adverse | 1/6407 (<0.1%) | 8/6414 (0.1%) | 7.92 (0.99–63.34) | 0.05 |
| Serum potassium >5.5 mmol/L (hyperkalemia) | Adverse | 125/6220 (2.0%) | 177/6230 (2.8%) | 1.41 (1.12–1.77) | 0.003 |
| Arrhythmia | Adverse | 68 (1.1%) | 69 (1.1%) | 1.01 (0.72–1.41) | 0.95 |
| Electrolyte abnormality | Adverse | 35 (0.6%) | 36 (0.6%) | 1.03 (0.65–1.64) | 0.91 |
| Injurious fall | Adverse | 61 (1.0%) | 65 (1.0%) | 1.06 (0.75–1.51) | 0.74 |
| Syncope | Adverse | 10 (0.2%) | 10 (0.2%) | 1.00 (0.41–2.39) | 0.99 |
| Acute renal failure | Adverse | 5 (0.1%) | 4 (0.1%) | 0.79 (0.21–2.95) | 0.73 |
| Serum sodium <130 mmol/L | Adverse | 47 (0.8%) | 46 (0.7%) | 0.97 (0.65–1.46) | 0.89 |
| Serum sodium >150 mmol/L | Adverse | 25 (0.4%) | 22 (0.4%) | 0.88 (0.49–1.56) | 0.65 |
| Serum potassium <3.0 mmol/L | Adverse | 33 (0.5%) | 32 (0.5%) | 0.90 (0.57–1.58) | 0.90 |
Criticisms
- Open-label design (PROBE) — knowledge of BP target could influence medication adjustments, lifestyle counseling, and other cardiovascular interventions differentially between arms.
- Only ~60% of intensive-group patients achieved SBP <120 mmHg — significant non-attainment dilutes the true effect size. The ITT analysis reflects the 'offer' of intensive treatment, not the actual achievement.
- Conducted entirely in China — Chinese populations have different stroke subtypes (more intracranial atherosclerosis, hemorrhagic stroke), dietary salt intake, body composition, and medication responses. Generalizability to Western populations is uncertain (acknowledged by authors).
- No mortality benefit — the absence of all-cause mortality reduction (HR 0.95) despite a 21% CV event reduction raises questions about competing risks and mechanism.
- COVID-19 pandemic overlap (enrollment 2019–2021) — remote/telephone visits during lockdowns may have affected BP measurement accuracy, medication adherence monitoring, and outcome ascertainment.
- Modest DBP difference between groups may confound interpretation — it's unclear whether the benefit is from SBP reduction specifically or from overall BP lowering.
- Only fatal or nonfatal stroke reached individual significance (HR 0.79, 95% CI 0.67–0.92) among the components of the primary composite; MI, HF, and CV death were directionally favorable but individually non-significant. Secondary outcomes were not formally adjusted for multiplicity.
- Choice of antihypertensive agents was not standardized — left to treating physicians, introducing variability in drug classes (some agents like ACE inhibitors may have diabetes-specific benefits beyond BP lowering).
- Symptomatic hypotension (HR 7.92) and hyperkalemia (HR 1.41) were significantly more frequent with intensive control, requiring active safety monitoring in clinical practice.
- Kidney outcomes did not show benefit with intensive control — CKD progression and CKD development trended numerically higher in the intensive group (not statistically significant); only incident albuminuria favored intensive treatment.
Funding
National Key Research and Development Program from the Ministry of Science and Technology of China and others
Based on: BPROAD (The New England Journal of Medicine, 2025)
Authors: Bi Y, Li M, Liu Y, ..., Wang W
Citation: Bi Y, Li M, Liu Y, et al. Intensive Blood-Pressure Control in Patients with Type 2 Diabetes. N Engl J Med 2025;392:1155–1167.
Content summarized and formatted by NeuroTrials.ai.