A meta-analysis of the long-term effects of antihypertensive therapy on the risk of major cardiovascular disease across 51 randomized trials.

Blood pressure (BP)-lowering therapy reduces cardiovascular risk, but whether its proportional benefits increase with longer treatment duration remains unclear. We conducted an individual participant-level data meta-analysis of 51 randomized trials from the Blood Pressure Lowering Treatment Trialists' Collaboration (358,642 participants; median follow-up: 4.2 years). Using Cox proportional hazards models, we estimated time-stratified hazard ratios (HRs) for major cardiovascular events (MACE; fatal or non-fatal stroke, ischemic heart disease or heart failure) across annual follow-up intervals up to more than 5 years, standardized to a 5-mmHg systolic BP reduction. Network meta-analysis examined whether temporal patterns differed across antihypertensive drug classes. Annual MACE incidence was highest during year 1 (3.0% treatment versus 3.6% control), declined during years 1-5 and then rose at more than 5 years (3.1% versus 3.4%). BP lowering reduced MACE risk, with benefits established early and not progressively increasing over time. A 5-mmHg systolic BP reduction was associated with a 12% lower MACE risk in year 1 (HR = 0.88, 95% confidence interval (CI): 0.84-0.91), with modest attenuation thereafter: HRs were 0.88 (0.85-0.92) in years 1-2, 0.94 (0.90-0.98) in years 2-3, 0.87 (0.83-0.92) in years 3-4, 0.97 (0.91-1.03) in years 4-5 and 0.94 (0.87-1.01) at more than 5 years (P for trend = 0.006). Similar patterns occurred across five drug classes. These findings indicate that the relative cardiovascular benefits of BP lowering emerge within months and do not increase over time, suggesting that prioritizing higher-risk individuals for treatment yields greater clinical utility than prolonged treatment in low-risk individuals.