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 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 should, therefore, be considered an important treatment option regardless of age, with the removal of age-related blood-pressure thresholds from international guidelines.

Funding

British Heart Foundation, National Institute of Health Research Oxford Biomedical Research Centre, Oxford Martin School.

中文翻译：

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降压药物治疗预防心血管疾病和死亡的年龄分层和血压分层效果：个体参与者级别的数据荟萃分析

 背景

药物降压对 70 岁及以上人群心血管结局的影响尚不确定，特别是在血压没有大幅升高的情况下。我们比较了按年龄和基线血压分层的患者组中降压治疗对主要心血管事件风险的影响。

 方法

我们使用来自药物降压与安慰剂或其他类别降压药物的随机对照试验的个体参与者水平数据，或者更多与更少强化治疗策略之间的数据进行了荟萃分析，其中至少有 1000每个治疗组的随访人年数。有心力衰竭病史的参与者被排除在外。数据来自降血压治疗试验者合作组织。我们汇总了数据，并将参与者分为基线年龄组（<55 岁、55-64 岁、65-74 岁、75-84 岁和 ≥85 岁）和血压类别（从 <120 mm 开始按 10 mm Hg 递增） Hg 至 ≥170 mm Hg 收缩压和从 <70 mm Hg 至 ≥110 mm Hg 舒张压）。我们使用固定效应一阶段方法并应用 Cox 比例风险模型（通过试验分层）来分析数据。主要结局被定义为致命性或非致命性中风、致命性或非致命性心肌梗死或缺血性心脏病、或导致死亡或需要住院的心力衰竭的复合结果。

 发现

我们纳入了来自 51 项随机临床试验的 358,707 名参与者的数据。随机分组参与者的年龄范围为 21 岁至 105 岁（中位数 65 岁 [IQR 59–75]），其中 42 960 名 (12·0%) 参与者年龄小于 55 岁，128 437 名 (35·8%) 年龄为 55 岁–64 岁，128 506 (35·8%) 65–74 岁，54 016 (15·1%) 75–84 岁，以及 4788 (1·3%) 85 岁及以上。每个年龄组的收缩压每降低 5 mm Hg，发生主要心血管事件的风险比在 55 岁以下的个体中为 0·82 (95% CI 0·76–0·88)，在 55 岁以下的个体中为 0·91 (95% CI 0·76–0·88)。 55-64岁的人为0·88-0·95)，65-74岁的人为0·91(0·88-0·95)，65-74岁的人为0·91(0·87-0·96) 75-84 岁的人群为 0·99 (0·87–1·12)，85 岁及以上的人群为 0·99 (0·87–1·12)（调整后的 p_交互作用=0·050）。舒张压每降低 3 毫米汞柱，就会观察到类似的比例风险降低模式。主要心血管事件的绝对风险降低因年龄而异，且老年组的降低幅度更大（调整后的p_相互作用=0·024）。我们没有发现任何年龄组不同基线血压类别的相对治疗效果存在任何有临床意义的异质性的证据。

 解释

药物降压对老年有效，没有证据表明预防主要心血管事件的相对风险降低因随机分组的收缩压或舒张压水平而异，低至低于 120/70 mm Hg。因此，无论年龄如何，药物降压都应被视为重要的治疗选择，国际指南中删除了与年龄相关的血压阈值。

 资金

英国心脏基金会、国家健康研究所牛津生物医学研究中心、牛津马丁学院。