Falk Jamie M, Froentjes Liesbeth, Kirkwood Jessica Em, Heran Balraj S, Kolber Michael R, Allan G Michael, Korownyk Christina S, Garrison Scott R
College of Pharmacy, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.
Department of Family Medicine, University of Alberta, Edmonton, Canada.
Cochrane Database Syst Rev. 2024 Dec 17;12(12):CD011575. doi: 10.1002/14651858.CD011575.pub3.
This is an update of the original Cochrane review, published in 2017. Eight out of 10 major antihypertensive trials in adults, 65 years of age or older, attempted to achieve a target systolic blood pressure (BP) of < 160 mmHg. Collectively, these trials demonstrated cardiovascular benefit for treatment, compared to no treatment, for older adults with BP > 160 mmHg. However, an even lower BP target of < 140 mmHg is commonly applied to all age groups. Yet the risk and benefit of antihypertensive therapy can be expected to vary across populations, and some observational evidence suggests that older adults who are frail might have better health outcomes with less aggressive BP lowering. Current clinical practice guidelines are inconsistent in target BP recommendations for older adults, with systolic BP targets ranging from < 130 mmHg to < 150 mmHg. The 2017 review did not find compelling evidence of a reduction in any of the primary outcomes, including all-cause mortality, stroke, or total serious cardiovascular adverse events, comparing a lower BP target to a higher BP target in older adults with hypertension. It is important to update this review to explore if new evidence exists to determine whether older adults might do just as well, better, or worse with less aggressive pharmacotherapy for hypertension.
To assess the effects of a less aggressive blood pressure target (in the range of < 150 to 160/95 to 105 mmHg), compared to a conventional or more aggressive BP target (of < 140/90 mmHg or lower) in hypertensive adults, 65 years of age or older.
For this update, Cochrane Hypertension's Information Specialist searched the following databases for randomised controlled trials up to June 2024: Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE Ovid, and Embase Ovid, and the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov for ongoing trials. We also contacted authors of relevant papers requesting information on further published and unpublished work. The searches had no language restrictions.
We included randomised trials of hypertensive older adults (≥ 65 years) that spanned at least one year, and reported the effect on mortality and morbidity of a higher or lower systolic or diastolic BP treatment target. Higher BP targets ranged from systolic BP < 150 to 160 mmHg or diastolic BP < 95 to 105 mmHg; lower BP targets were 140/90 mmHg or lower, measured in an ambulatory, home, or office setting.
Two authors independently screened and selected trials for inclusion, assessed risk of bias and certainty of the evidence, and extracted data. We combined data for dichotomous outcomes using the risk ratio (RR) with 95% confidence interval (CI). For continuous outcomes, we used mean difference (MD). Primary outcomes were all-cause mortality, stroke, institutionalisation, and serious cardio-renal vascular adverse events. Secondary outcomes included cardiovascular mortality, non-cardiovascular mortality, unplanned hospitalisation, each component of cardiovascular serious adverse events separately (including cerebrovascular disease, cardiac disease, vascular disease, and renal failure), total serious adverse events, total minor adverse events, withdrawals due to adverse effects, systolic BP achieved, and diastolic BP achieved.
With the addition of one new trial, we included four trials in this updated review (16,732 older adults with a mean age of 70.3 years). Of these, one trial used a combined systolic and diastolic BP target and compared a higher target of < 150/90 mmHg to a lower target of < 140/90 mmHg, and two trials utilised a purely systolic BP target, and compared a systolic BP < 150 mmHg (1 trial) and a systolic BP < 160 mmHg (1 trial), to a systolic BP < 140 mmHg. The fourth and newest trial also utilised a systolic BP target, but also introduced a lower limit for systolic BP. It compared systolic BP in the target range of 130 to 150 mmHg to a lower target range of 110 to 130 mmHg. The evidence shows that treatment to the lower BP target over two to four years may result in little to no difference in all-cause mortality (RR 1.14, 95% CI 0.95 to 1.37; 4 studies, 16,732 participants; low-certainty evidence), but the lower BP target does reduce stroke (RR 1.33, 95% CI 1.06 to 1.67; 4 studies, 16,732 participants; high-certainty evidence), and likely reduces total serious cardiovascular adverse events (RR 1.25, 95% CI 1.09 to 1.45; 4 studies, 16,732 participants; moderate-certainty evidence). Adverse effects were not available from all trials, but the lower BP target likely does not increase withdrawals due to adverse effects (RR 0.99, 95% CI 0.74 to 1.33; 3 studies, 16,008 participants; moderate-certainty evidence).
AUTHORS' CONCLUSIONS: When comparing a higher BP target, in the range of < 150 to 160/95 to 105 mmHg, to a lower BP target of 140/90 or lower, over two to four years of follow-up, there is high-certainty evidence that the lower BP target reduces stroke, and moderate-certainty evidence that the lower BP target likely reduces serious cardiovascular events. The effect on all-cause mortality is unclear (low-certainty evidence), and the lower BP target likely does not increase withdrawals due to adverse effects (moderate-certainty evidence). Although additional research is warranted in those who are 80 years of age and older, and those who are frail (in whom risks and benefits may differ), conventional BP targets may be appropriate for the majority of older adults.
这是2017年发表的原始Cochrane系统评价的更新版。在针对65岁及以上成年人的10项主要抗高血压试验中,有8项试图将收缩压(BP)目标值降至<160 mmHg。总体而言,这些试验表明,与未治疗相比,对于收缩压>160 mmHg的老年人,治疗具有心血管益处。然而,目前普遍将<140 mmHg的更低血压目标应用于所有年龄组。然而,抗高血压治疗的风险和益处可能因人群而异,一些观察性证据表明,身体虚弱的老年人血压降低幅度较小可能会有更好的健康结果。目前的临床实践指南对于老年人的血压目标建议并不一致,收缩压目标范围从<130 mmHg到<150 mmHg。2017年的系统评价未发现有令人信服的证据表明,在高血压老年患者中,较低血压目标与较高血压目标相比,在任何主要结局方面有所降低,包括全因死亡率、中风或总的严重心血管不良事件。更新此系统评价以探索是否有新证据来确定老年患者采用不太积极的高血压药物治疗效果是否一样好、更好或更差,这一点很重要。
评估与常规或更积极的血压目标(<140/90 mmHg或更低)相比,不太积极的血压目标(收缩压<150至160 mmHg和舒张压<95至105 mmHg)对65岁及以上高血压成年人的影响。
对于此次更新,Cochrane高血压组的信息专家检索了以下数据库以获取截至2024年6月的随机对照试验:Cochrane高血压专业注册库、CENTRAL、MEDLINE Ovid、Embase Ovid以及美国国立卫生研究院正在进行的试验注册库ClinicalTrials.gov以获取正在进行的试验。我们还联系了相关论文的作者,索取有关进一步已发表和未发表研究的信息。检索无语言限制。
我们纳入了跨度至少一年的高血压老年患者(≥65岁)随机试验,并报告了较高或较低收缩压或舒张压治疗目标对死亡率和发病率的影响。较高血压目标范围为收缩压<150至160 mmHg或舒张压<95至105 mmHg;较低血压目标为140/90 mmHg或更低,在动态、家庭或办公室环境中测量。
两位作者独立筛选并选择纳入试验,评估偏倚风险和证据的确定性,并提取数据。我们使用风险比(RR)及95%置信区间(CI)合并二分法结局的数据。对于连续性结局,我们使用均值差(MD)。主要结局为全因死亡率、中风、入住机构和严重的心肾血管不良事件。次要结局包括心血管死亡率、非心血管死亡率、非计划住院、心血管严重不良事件的各个组成部分(包括脑血管疾病、心脏病、血管疾病和肾衰竭)、总的严重不良事件、总的轻微不良事件、因不良反应退出研究、达到的收缩压和达到的舒张压。
新增一项试验后,本次更新的系统评价纳入了四项试验(16,732名老年患者,平均年龄70.3岁)。其中,一项试验使用了收缩压和舒张压联合目标,比较了较高目标<150/90 mmHg与较低目标<140/90 mmHg,两项试验采用了单纯收缩压目标,分别比较了收缩压<150 mmHg(一项试验)和收缩压<160 mmHg(一项试验)与收缩压<140 mmHg。第四项也是最新的试验也采用了收缩压目标,但还引入了收缩压下限。它比较了目标范围为130至150 mmHg的收缩压与较低目标范围为110至130 mmHg的收缩压。证据表明,在两到四年内将血压降至较低目标可能在全因死亡率方面几乎没有差异(RR 1.14,95% CI 0.95至1.37;4项研究,16,732名参与者;低确定性证据),但较低血压目标确实可降低中风发生率(RR 1.33,95% CI 1.06至1.67;4项研究,16,732名参与者;高确定性证据),并可能降低总的严重心血管不良事件(RR 1.25,95% CI 1.09至1.45;4项研究,16,732名参与者;中度确定性证据)。并非所有试验都提供了不良反应数据,但较低血压目标可能不会增加因不良反应而退出研究的比例(RR 0.99,95% CI 0.74至1.33;3项研究,16,008名参与者;中度确定性证据)。
在两到四年的随访中,将较高血压目标(收缩压<150至160 mmHg和舒张压<95至105 mmHg)与较低血压目标140/90或更低进行比较时,有高确定性证据表明较低血压目标可降低中风发生率,有中度确定性证据表明较低血压目标可能降低严重心血管事件。对全因死亡率的影响尚不清楚(低确定性证据),且较低血压目标可能不会增加因不良反应而退出研究的比例(中度确定性证据)。尽管80岁及以上老年人以及身体虚弱者(其风险和益处可能不同)仍需进一步研究,但常规血压目标可能适用于大多数老年人。