Contrary to existing international guidelines on age-related blood-pressure thresholds, a meta-analysis in The Lancet found that pharmacological blood pressure reduction is effective into old age, with no evidence that relative risk reductions for prevention of major cardiovascular events varied by baseline systolic or diastolic blood pressure levels, down to less than 120/70 mm Hg.
With ageing populations, one increasingly important uncertainty of the effects of blood-pressure-lowering pharmacotherapy is whether treatment should be initiated in, and continued into, older age (70 and older), mainly when blood pressure is within the normal range.
Research in context
We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov covering the period between 1 January 1966, and 1 September 2019, with no language restrictions, for randomised controlled trials investigating blood-pressure-lowering drug treatment. We searched MEDLINE using and expanding on the MeSH terms for “hypertension”, “blood pressure”, and “antihypertensive agents”, including possible variations thereof as well as relevant antihypertensive drug classes.
We identified several individual randomised controlled trials and meta-analyses with age-stratified effects of blood-pressure-lowering treatment but no reports with concurrent age and blood pressure stratification at the individual level. Additionally, evidence on treatment effects in individuals older than 85 years and with normal or mildly increased blood pressure was scarce.
Added value of this study
We gathered individual participant-level data from eligible large-scale trials of blood-pressure-lowering treatment. With access to individual participant-level data from 358 707 randomised participants from 51 trials (with 22 000 participants aged ≥80 years), this study enabled detailed investigation of age-stratified and blood-pressure-stratified effects on major cardiovascular events and death.
We found pharmacological blood pressure reduction to be effective across a wide range of ages with no evidence that relative risk reductions for prevention of major cardiovascular events varied by baseline systolic or diastolic blood pressure levels, down to less than 120/70 mm Hg.
Although we found evidence for diminishing relative risk reductions with increasing age and limited statistical power for detection of an effect in the oldest age group in isolation (90 years at the end of the study), absolute risk reductions did not follow the same pattern and appeared to be even larger in the older age groups. Stratified effects on all-cause death followed a similar pattern, with no evidence to suggest treatment increases mortality in any age group.
Implications of all the available evidence
This detailed study of age-stratified and blood-pressure-stratified effect of antihypertensive medication provides compelling evidence for the effectiveness of pharmacological blood pressure reduction into old age irrespective of baseline systolic or diastolic blood pressure. These findings challenge the common approach of withholding antihypertensive treatment for older adults, in particular when their blood pressure is not highly abnormal. Treatment should, therefore, be considered an important option regardless of age with removal of age-related blood-pressure thresholds from international guidelines.
Study details
Age-stratified and blood-pressure-stratified effects of blood-pressure-lowering pharmacotherapy for the prevention of cardiovascular disease and death: an individual participant-level data meta-analysis
The Blood Pressure Lowering Treatment Triallists' Collaboration
Published in The Lancet on 26 August 2021
Summary
Background
The effects of pharmacological blood-pressure-lowering on cardiovascular outcomes in individuals aged 70 years and older, particularly when blood pressure is not substantially increased, is uncertain. We compared the effects of blood-pressure-lowering treatment on the risk of major cardiovascular events in groups of patients stratified by age and blood pressure at baseline.
Methods
We did a meta-analysis using individual participant-level data from randomised controlled trials of pharmacological blood-pressure-lowering versus placebo or other classes of blood-pressure-lowering medications, or between more versus less intensive treatment strategies, which had at least 1000 persons-years of follow-up in each treatment group. Participants with previous history of heart failure were excluded.
Data were obtained from the Blood Pressure Lowering Treatment Triallists' Collaboration. We pooled the data and categorised participants into baseline age groups (<55 years, 55–64 years, 65–74 years, 75–84 years, and ≥85 years) and blood pressure categories (in 10 mm Hg increments from <120 mm Hg to ≥170 mm Hg systolic blood pressure and from <70 mm Hg to ≥110 mm Hg diastolic).
We used a fixed effects one-stage approach and applied Cox proportional hazard models, stratified by trial, to analyse the data. The primary outcome was defined as either a composite of fatal or non-fatal stroke, fatal or non-fatal myocardial infarction or ischaemic heart disease, or heart failure causing death or requiring hospital admission.
Findings
We included data from 358 707 participants from 51 randomised clinical trials. The age of participants at randomisation ranged from 21 years to 105 years (median 65 years [IQR 59–75]), with 42 960 (12·0%) participants younger than 55 years, 128 437 (35·8%) aged 55–64 years, 128 506 (35·8%) 65–74 years, 54 016 (15·1%) 75–84 years, and 4788 (1·3%) 85 years and older.
The hazard ratios for the risk of major cardiovascular events per 5 mm Hg reduction in systolic blood pressure for each age group were 0·82 (95% CI 0·76–0·88) in individuals younger than 55 years, 0·91 (0·88–0·95) in those aged 55–64 years, 0·91 (0·88–0·95) in those aged 65–74 years, 0·91 (0·87–0·96) in those aged 75–84 years, and 0·99 (0·87–1·12) in those aged 85 years and older (adjusted pinteraction=0·050). Similar patterns of proportional risk reductions were observed for a 3 mm Hg reduction in diastolic blood pressure. Absolute risk reductions for major cardiovascular events varied by age and were larger in older groups (adjusted pinteraction=0·024). We did not find evidence for any clinically meaningful heterogeneity of relative treatment effects across different baseline blood pressure categories in any age group.
Interpretation
Pharmacological blood pressure reduction is effective into old age, with no evidence that relative risk reductions for prevention of major cardiovascular events vary by systolic or diastolic blood pressure levels at randomisation, down to less than 120/70 mm Hg.
Pharmacological blood pressure reduction should, therefore, be considered an important treatment option regardless of age, with the removal of age-related blood-pressure thresholds from international guidelines.
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