A meta-analysis of the long-term effects of antihypertensive therapy on the risk of major cardiovascular disease across 51 randomized trials
Blood pressure-lowering treatment reduced cardiovascular events quickly, but relative benefits did not grow with longer treatment.
*Individual participant data meta-analysis of randomized trials; Level 1.
Citation
Yang Q, Bidel Z, Canoy D, et al. A meta-analysis of the long-term effects of antihypertensive therapy on the risk of major cardiovascular disease across 51 randomized trials. Nature Medicine. 2026. doi:10.1038/s41591-026-04514-3
Background
Blood pressure medicines are known to prevent heart attacks, strokes, heart failure, and cardiovascular death. This study tested whether benefits become proportionally larger the longer treatment continues.
Patients
357,314 adults from 51 randomized trials. People with heart failure at study start and those missing key follow-up data were excluded.
Intervention
Blood pressure-lowering treatment, analyzed as a 5 mmHg lower systolic blood pressure.
Control
Placebo, less intensive treatment, or a treatment strategy with smaller blood pressure reduction.
Outcome
Major cardiovascular events: fatal or nonfatal stroke, ischemic heart disease, or heart failure. Death outcomes were also assessed.
Follow-up Period
Median 4.2 years.
Results
| Outcome | Key result |
|---|---|
| Major cardiovascular events, year 1 (primary) | 12% lower risk; hazard ratio 0.88 (95% confidence interval 0.84–0.91) |
| Major cardiovascular events, 5 years (primary) | Absolute reduction 1.25%; number needed to treat 80 |
| Stroke, 5 years | Absolute reduction 0.52%; number needed to treat 192 |
| Heart failure, year 1 | 27% lower risk; hazard ratio 0.73 (95% confidence interval 0.65–0.80) |
| Death from any cause, overall | 4% lower risk; hazard ratio 0.96 (95% confidence interval 0.94–0.99) |
Major cardiovascular event reductions were significant early, but years 4–5 and beyond 5 years were not significant. Analyses followed intention-to-treat principles. Absolute benefit accumulated over time, but proportional benefit did not compound.
Limitations
Median follow-up may be too short to detect very long-term effects. Later follow-up included only survivors without earlier events, which can bias time-specific comparisons. Participants were mostly older adults, so results should not be extended to young, low-risk adults.
Funding
British Heart Foundation; no reported funder role.
Clinical Application
Treat based on cardiovascular risk; do not medicate low-risk patients solely expecting larger benefits from earlier, longer therapy.
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