While major guidelines recommend intensive blood pressure control, the overall balance of benefits and harms has remained uncertain. A new post-hoc, pooled analysis of six major randomised controlled trials has quantified these trade-offs, finding that intensive treatment provides a net clinical benefit over standard control, despite an increase in adverse events.¹

Researchers from the Blood Pressure Reduction Union-Landmark Evidence (BPRULE) Study Group conducted a pooled participant-level analysis of six randomised controlled trials: ACCORD BP, SPRINT, ESPRIT, BPROAD, STEP, and CRHCP.² The analysis included 80,220 participants (median age 64.0 years; 48.7% male) who were randomised to either intensive blood pressure treatment (systolic blood pressure [SBP] target <120 mm Hg or <130 mm Hg) or standard treatment (SBP target <140 mm Hg, <150 mm Hg in older adults, or usual care).

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, such as hypotension and syncope, and renal-related events.

Over a median follow-up of 3.2 years, the primary composite cardiovascular outcome occurred in 5.3% of participants in the intensive control group compared to 7.1% in the standard control group (hazard ratio 0.76; 95% credible interval [CrI] 0.72–0.81; p<0.0001). This translated to a 1.73% absolute risk reduction in cardiovascular disease, with a number needed to treat of 58.

However, intensive control was associated with a 1.82% absolute risk increase for adverse events of interest, with a number needed to harm of 55. Despite the similar numbers needed to treat and harm, the overall analysis showed a favourable benefit–harm profile for intensive treatment, 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).

The findings suggest that while intensive blood pressure lowering increases the risk of certain adverse events, this is outweighed by the reduction in major cardiovascular events. The BPRULE Study Group concluded, “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.”¹ This analysis provides further support for current guideline recommendations favouring more intensive blood pressure targets in appropriate patient populations.

References

1. Guo X, Sun G, Xu Y, et al. 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. Lancet. 2025. https://doi.org/10.1016/S0140-6736(25)01391-1.

2. Wright JT Jr, Williamson JD, Whelton PK, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103-2116. https://doi.org/10.1056/NEJMoa1511939.

This study was funded by 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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