Benefit–harm trade-offs of intensive blood pressure control versus standard blood pressure control on cardiovascular and renal outcomes: an individual participant data analysis of randomised controlled trials

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.