Key result
Intensive BP control cuts major CV events by ~24% vs. standard control.
Why the study?
The overall benefit-harm balance of guideline-recommended intensive blood pressure control remained uncertain, particularly regarding how net clinical benefit varies by target and patient characteristics.
Does intensive blood pressure control reduce the composite of myocardial infarction, stroke, heart failure, and cardiovascular death compared to standard blood pressure control?
Meta-Analysis (n=80,220)
Randomized
Yes
Does intensive blood pressure control reduce the composite of myocardial infarction, stroke, heart failure, and cardiovascular death compared to standard blood pressure control?
Hazard Ratio: 0.76 (95% CI 0.72–0.81)
Absolute Event Rate: 5.3% vs 7.1%
Absolute Risk Reduction: 1.73%
Number Needed to Treat: 58
p-value: p=<0.0001
Intensive blood pressure control provides a net clinical benefit, significantly reducing cardiovascular events despite a quantifiable increase in adverse and renal events.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The relationship between BP and cardiovascular risk appears more complex than a simple linear association; a so-called J-curve phenomenon has been described to indicate the increased risk associated with lower BP targets, which may vary based on patient characteristics and comorbidities. These observations underscore the need for a nuanced, patient-centred approach that balances potential benefits against the risk of adverse events. The debate is further complicated by geographic and ethnic variability in achieving BP levels and treatment responses, as most recent large-scale studies have predominantly involved Asian populations. Consequently, extrapolating the benefits of aggressive BP control to European or multi-ethnic cohorts remains unjustified.”
“Meta-analyses of biased RCTs give biased results, even on individual data”
“Compared with standard blood pressure control, intensive blood pressure control provides a net benefit between the reduction in cardiovascular events and the increase in adverse events, including renal events.”
Intensive BP lowering warrants individualized targets weighing CV gains against renal risks; extends RCT meta-analysis evidence on optimal thresholds.
BACKGROUND Although intensive blood pressure control is recommended by major guidelines, its overall benefit-harm balance remains uncertain. In particular, it is unclear how net clinical benefit varies by blood pressure target and patient characteristics. We aimed to quantify the benefit-harm trade-offs of intensive blood pressure control versus standard blood pressure control. METHODS We conducted a post-hoc, pooled participant-level analysis of six randomised controlled trials (ACCORD BP, SPRINT, ESPRIT, BPROAD, STEP, and CRHCP). Trial selection was based on our collaborative framework, the Blood Pressure Reduction Union-Landmark Evidence, and a targeted literature search, guided by five predefined inclusion criteria: (1) comparison of intensive systolic blood pressure targets (<120 mm Hg or <130 mm Hg) versus standard treatment; (2) reporting of composite major cardiovascular outcomes; (3) enrolment of more than 2000 participants; (4) standardised reporting of treatment-related adverse events; and (5) availability of individual participant data. We also conducted a systematic review in which we searched PubMed for studies published from database inception up to June 15, 2025, with no language restrictions. We used search terms related to cardiovascular outcomes, hypertension, intensive blood pressure lowering, and randomised trials. Study screening and data extraction were independently conducted in pairs by ten reviewers, with discrepancies resolved by discussion or adjudication. Participants in the six trials were randomly assigned to intensive blood pressure treatment (systolic blood pressure target <120 mm Hg or <130 mm Hg) versus standard treatment (systolic blood pressure target <140 mm Hg, <150 mm Hg in older adults, or usual care), depending on the trial design. The primary benefit outcome was a composite of myocardial infarction, stroke, heart failure, and cardiovascular death. The primary harm outcomes were adverse events of interest (eg, hypotension and syncope) and renal-related events. Statistical analyses were performed on an intention-to-treat basis using Bayesian hierarchical models. FINDINGS The initial dataset included 80 676 participants, of whom 80 220 were included in our analyses (intensive blood pressure control group n=40 503; standard blood pressure control group n=39 717). The median age was 64·0 years (IQR 59·0-70·0), 39 043 (48·7%) participants were male, and 41 177 (51·3%) were female. Most participants were Asian (66 290 [82·6%]) or White (8097 [10·1%]). During a median follow-up of 3·2 years (IQR 3·0-3·5), the composite cardiovascular disease outcome occurred in 2158 (5·3%) participants in the intensive blood pressure control group and 2811 (7·1%) participants in the standard blood pressure control group (hazard ratio 0·76, 95% credible interval [CrI] 0·72-0·81; p<0·0001). Compared with standard blood pressure control, intensive blood pressure control was associated with a 1·73% absolute risk reduction (95% CrI 1·65-1·81) in cardiovascular disease (number needed to treat 58 [95% CrI 55-61]) and a 1·82% absolute risk increase (95% CrI 1·63-2·01) for adverse events of interest (number needed to harm 55 [95% CrI 49-61]). Overall, intensive blood pressure control showed a favourable benefit-harm profile, with a net benefit of 1·14 (95% CrI 1·03-1·25), using adjudicated weighting. The net benefit remained positive when considering kidney-related adverse events (1·13 [95% CrI 1·01-1·24]). INTERPRETATION Compared with standard blood pressure control, intensive blood pressure control provides a net benefit between the reduction in cardiovascular events and the increase in adverse events, including renal events. FUNDING National Key Research and Development Program, the Ministry of Science and Technology of China; National Science and Technology Major Project; National Natural Science Foundation of China; China Academy of Chinese Medical Sciences Innovation Fund for Medical Science; and Science and Technology Program of Liaoning Province.
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Guo et al. (2025) conducted a meta-analysis in Hypertension (n=80,220). Intensive blood pressure control vs. Standard blood pressure control was evaluated on Composite of myocardial infarction, stroke, heart failure, and cardiovascular death (HR 0.76, 95% CI 0.72-0.81, p=<0.0001). Intensive blood pressure control reduced myocardial infarction, stroke, heart failure, and cardiovascular death compared to standard control (HR 0.76; 95% CrI 0.72-0.81; p<0.0001).
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