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.
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.
复制标题
DOI：
10.1016/s0140-6736(21)01921-8
复制
发表时间：
2021-09-18
期刊：
影响因子：
--
通讯作者：
Blood Pressure Lowering Treatment Trialists' Collaboration
中科院分区：
文献类型：
--
作者：
Blood Pressure Lowering Treatment Trialists' Collaboration
药物降压对70岁及以上人群心血管结局的影响尚不确定，尤其是当血压未显著升高时。我们在按年龄和基线血压分层的患者组中比较了降压治疗对主要心血管事件风险的影响。我们使用来自随机对照试验的个体参与者水平数据进行了荟萃分析，这些随机对照试验比较了药物降压与安慰剂或其他类别的降压药物，或更多与更少的强化治疗策略，每个治疗组至少有1000人-年的随访。排除既往有心力衰竭史的受试者。数据来自降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（收缩压<120 mm Hg至≥170 mm Hg，舒张压<70 mm Hg至≥ 110 mm Hg，以10 mm Hg为增量）。我们使用固定效应一步法，并应用考克斯比例风险模型，按试验分层，分析数据。主要结局定义为致死性或非致死性卒中、致死性或非致死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终点。我们纳入了来自51项随机临床试验的358707名参与者的数据。参与者随机分组时的年龄范围为21岁至105岁（中位数65岁[IQR 59-75]），42 960（12.0%）例受试者年龄小于55岁，128 437（35.8%）例受试者年龄为55-64岁，128 506（35.8%）例受试者年龄为65-74岁，75-84岁54016人（15.1%），85岁及以上4788人（1.3%）。各年龄组收缩压每降低5 mm Hg，主要心血管事件风险的风险比为0.82（95% CI 0.76 - 0.88）在年龄小于55岁的个体中，0.91（0.88 - 0.95）55-64岁者，0.91（0.88 - 0.95）65-74岁者，0.91 75-84岁组（0·87-0·96），85岁及以上组（0·99）（0·87-1·12）（校正后的相互作用系数=0·050）。对于舒张压降低3 mm Hg，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，且在老年组中更大（校正的相互作用p = 0.024）。我们没有发现任何年龄组中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。药物降压对老年人有效，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时收缩压或舒张压水平而异，低于120/70 mm Hg。因此，无论年龄大小，药物降压都应被视为一种重要的治疗选择，并从国际指南中删除与年龄相关的血压阈值。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。
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. 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. 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. 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. British Heart Foundation, National Institute of Health Research Oxford Biomedical Research Centre, Oxford Martin School.