Long-Term Antihypertensive Therapy and MACE Risk Across 51 Trials

Key Takeaways

• A standardized 5-mmHg systolic blood pressure reduction was associated with lower major cardiovascular event risk as early as year 1.
• Time-stratified estimates remained directionally favorable but did not show progressively stronger relative benefit with longer therapy, with a significant trend toward attenuation over time.
• Similar temporal patterns were seen across five drug classes, and the authors tied clinical utility more to risk selection than longer treatment in lower-risk groups.

A 5-mmHg systolic blood pressure reduction was associated with a 12% lower risk of major cardiovascular events in year 1 in an individual participant-level meta-analysis published in Nature Medicine. The analysis pooled 51 randomized trials and 358,642 participants.

Individual participant-level data from the Blood Pressure Lowering Treatment Trialists’ Collaboration spanned 51 randomized trials with 358,642 participants and a median follow-up of 4.2 years. Major cardiovascular events were defined as fatal or non-fatal stroke, ischemic heart disease, or heart failure. Cox proportional hazards models estimated time-stratified hazard ratios across annual follow-up intervals through more than 5 years, standardized to a 5-mmHg systolic blood pressure reduction.

Annual major cardiovascular event incidence was 3.0% with treatment and 3.6% with control during year 1. Incidence then declined during years 1 through 5 and rose beyond 5 years to 3.1% versus 3.4%. Those event rates provided absolute context for the interval-based estimates. Standardized hazard ratios were 0.88 (95% CI 0.84-0.91) in year 1 and 0.88 (0.85-0.92) in years 1 to 2. Subsequent estimates were 0.94 (0.90-0.98) in years 2 to 3, 0.87 (0.83-0.92) in years 3 to 4, 0.97 (0.91-1.03) in years 4 to 5, and 0.94 (0.87-1.01) beyond 5 years. The sequence showed early relative risk reduction with modest attenuation later, a P for trend of 0.006, and no progressive step-up over time.

A network meta-analysis evaluated whether the temporal pattern varied across antihypertensive classes and found similar patterns across five classes. The timing pattern was not confined to a single drug category. The authors interpreted the findings as showing that relative cardiovascular benefit emerged within months and did not increase over time. They also framed greater clinical utility around prioritizing treatment in people at higher cardiovascular risk rather than extending treatment in lower-risk groups.