· Lancet (London, England) 2021 · individual participant-level data meta-analysis · n=344,716 participants (48 trials)

Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis.

Cited 1042 times in the scientific literature.

Level 1 - systematic review of randomized trials

Individual participant-level data meta-analysis of randomized controlled trials

PubMed 33933205 · doi:10.1016/S0140-6736(21)00590-0 · record verified 2026-08-29

What was done

An individual participant-level meta-analysis was performed on 48 randomized controlled trials (344,716 participants; median follow-up 4.15 years) assessing blood pressure-lowering drugs versus placebo, active comparators, or intensive versus standard regimens. Participants were stratified by pre-existing cardiovascular disease (CVD) status and across seven baseline systolic blood pressure (SBP) categories (<120 to ≥170 mm Hg). The primary endpoint was major cardiovascular events (composite of fatal/non-fatal stroke, fatal/non-fatal myocardial infarction or ischaemic heart disease, or fatal/hospitalized heart failure).

What was found

Per 5 mm Hg reduction in SBP, the hazard ratio for major cardiovascular events was 0.91 (95% CI 0.89–0.94) in participants without pre-existing CVD (incidence rate 25.9 vs 31.9 per 1,000 person-years) and 0.89 (95% CI 0.86–0.92) in those with pre-existing CVD (incidence rate 36.0 vs 39.7 per 1,000 person-years). Relative risk reductions were proportional to the magnitude of SBP reduction, with no evidence of effect heterogeneity across baseline SBP categories, extending down to <120 mm Hg.

Why it matters

Pharmacological blood pressure lowering consistently reduces cardiovascular risk even at normal and high-normal baseline blood pressure levels. This indicates that treatment decisions should focus on absolute cardiovascular risk rather than baseline blood pressure thresholds alone.

Limits

The analysis excluded studies conducted exclusively in heart failure or acute clinical settings. Studies spanned from 1972 to 2013, reflecting changing medical standards over four decades. Detailed data on adverse events, drug discontinuation, and specific antihypertensive drug classes across low baseline blood pressure subgroups were not reported in the abstract.

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