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

Abstract

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. MethodsWe 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. FindingsWe 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 p interaction =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 p interaction =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 ...

Seven‐action approaches for the management of hypertension in Asia – The HOPE Asia network

“… 44 In addition, these benefits of BP lowering were seen in individuals aged up to 85 years. 45 In the STEP study, a 5‐mmHg reduction in office SBP was associated with an 18% reduction in total cardiovascular disease risk, a 23% reduction in the risk of stroke and coronary artery disease, and a 58% reduction in heart failure risk. These findings showing greater reductions in cardiovascular risk in the STEP study than in SPRINT and the BPLTTC (Table 2 ), suggest that strict BP control is probably more effective for cardiovascular disease prevention in Asians than in Westerners.…”

STEP to blood pressure management of elderly hypertension: evidence from Asia

“…Impressive cardiovascular benefits have been observed with intensive BP control (SBP target, <120 mmHg), as compared with standard BP control (SBP target, <140 mmHg), in the SPRINT (Systolic Blood Pressure Intervention Trial), even in patients 75 years of age or older [ 7 , 8 ]. A most recent meta-analysis including 51 randomized trials with over 350,000 participants from the BPLTTC (The Blood Pressure Lowering Treatment Trialists’ Collaboration) showed that BP lowering is effective in older people for reducing major cardiovascular events, down to below 120/70 mmHg [ 9 ]. The STEP (Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients) study—a multicenter, randomized, controlled trial conducted in China, provided new direct evidence that intensive BP treatment (SBP target, 110 mmHg to <130 mmHg) benefits older hypertensive patients (aged 60-80 years) and reduces the incidence of cardiovascular events than standard treatment (target 130 mmHg to <150 mmHg) [ 10 ].…”

Commentary: “Lower is Better” — SPRINTing to STEPping up hypertension research? An historical perspective on hypertension trials

“…Over time, there was a steady shift of the age band of interest to more elderly patients and to lower blood pressure targets. A recently published meta-analysis [ 3 ] included 358,707 patients from 51 trials, aged 21–105 years (median, 65 years; interquartile range, 59–75 years). It showed no evidence for any clinically meaningful heterogeneity of relative risk reduction by blood-pressure lowering therapies across different baseline blood-pressure categories in any age group.…”

“…It showed no evidence for any clinically meaningful heterogeneity of relative risk reduction by blood-pressure lowering therapies across different baseline blood-pressure categories in any age group. Per 5-mm Hg systolic blood pressure reduction, the hazard ratios of major cardiovascular events were 0.82 (95% confidence interval, 0.76–0.88), 0.91 (0.88–0.95), 0.91 (0.88–0.95), 0.91 (0.87–0.96), and 0.99 (0.87–1.12) in the age bands <55 years, 55–64 years, 65–74 years, 75–84 years and ≥85 years with similar patterns of relative risk reduction per 3-mm Hg lower diastolic blood pressure [ 3 ]. However, the reductions in absolute risk produced by blood-pressure lowering increased with advancing age.…”

“…However, the reductions in absolute risk produced by blood-pressure lowering increased with advancing age. This meta-analysis [ 3 ], the post-trial evidence from SPRINT [ 1 ] and from the Systolic Hypertension in Europe Trial (Syst-Eur) [ 4 ] consolidated the concept that the benefits generated by antihypertensive treatment increased with earlier initiation of the pharmacological management of hypertension and lower blood pressure targets, as endorsed by the current American College of Cardiology/American Heart Association (ACC/AHA) guideline.…”