Pharmacological blood-pressure lowering for the prevention of cardiovascular disease and death across the full spectrum of chronic kidney disease severity: an individual-participant data meta-analysis.

We investigated the effect of blood-pressure-lowering treatment on the risk of major cardiovascular disease and death across the full spectrum of CKD stages and by key clinical subgroups.

我们研究了降压治疗对整个CKD阶段谱系以及关键临床亚组中主要心血管疾病和死亡风险的影响。

Methods

We conducted a one-stage meta-analysisof individual-participant data from RCTs in which participants were randomly assigned to a blood-pressure-lowering therapy versus a comparator.

我们进行了一项单阶段的随机对照试验(RCTs)个体参与者数据的荟萃分析，其中参与者被随机分配到降压治疗与对照组。

We used RCTs collated in the Blood Pressure Lowering Treatment Trialists' Collaboration dataset, published at any time in any language, which were eligible for inclusion if they had at least 1000 person-years of follow-up per arm, baseline blood-pressure and creatinine measurements, and time-to-event outcomes; those with unclear randomisation procedures or restricted to heart failure or acute care settings were excluded.

我们使用了血压降低治疗试验者合作组织数据集中整理的RCTs，这些研究可以是任何时间、任何语言发表的，如果它们每组至少有1000人年以上的随访时间、基线血压和肌酐测量以及时间到事件的结果；那些随机化程序不明确或仅限于心力衰竭或急性护理环境的研究被排除在外。

Participants with a documented history of heart failure or extreme creatinine values were excluded.

记录有心力衰竭病史或极端肌酐值的参与者被排除在外。

No age criteria were applied.

没有应用年龄标准。

The primary outcome was major cardiovascular events, defined as a composite of fatal or non-fatal stroke, ischaemic heart disease, or hospitalisation for, or death from, heart failure.

主要结果是重大心血管事件，定义为致命或非致命性中风、缺血性心脏病，或因心力衰竭住院或死亡的复合终点。

Relative treatment effects were estimated with a stratified Cox proportional hazards model.

使用分层Cox比例风险模型估计相对治疗效果。

Heterogeneity of treatment effects was evaluated across prespecified subgroups defined by CKD status, CKD stage (1-5), diabetes, proteinuria, and baseline blood pressure.

通过预先设定的亚组评估了治疗效果的异质性，这些亚组根据慢性肾脏病（CKD）状态、CKD分期（1-5）、糖尿病、蛋白尿和基线血压定义。

A stratified network meta-analysiswas performed to examine whether treatment effects differed by defined subgroups within each of five principal antihypertensive drug classes.

进行了分层的网络荟萃分析，以检查在五种主要降压药物类别中，治疗效果是否因定义的亚组而异。

The systematic reviewwas registered in PROSPERO (CRD42018099283).

该系统评价已在PROSPERO注册（CRD42018099283）。

Results

From 52 RCTs (363 684 participants), a total of 285 124 participants from 46 randomised trials met the eligibility criteria; 116 145 (40·7%) were women, 168 979 (59·3%) were men, 59 185 (20·7%) had CKD at baseline, and 86 067 (30·2%) had type 2 diabetes.

在52项随机对照试验（363,684名参与者）中，共有来自46项随机试验的285,124名参与者符合纳入标准；其中116,145名（40.7%）为女性，168,979名（59.3%）为男性，59,185名（20.7%）在基线时患有慢性肾脏病（CKD），86,067名（30.2%）患有2型糖尿病。

During a median follow-up of 4·4 years (IQR 3·2-5·1), a 5 mm Hg reduction in systolic blood pressure reduced the risk of major cardiovascular disease in individuals with CKD (hazard ratio[HR] 0·91 [95% CI 0·87-0·94]) and without CKD (0·90 [0·88-0·93]; pinteraction>0·99).

在中位随访4.4年（四分位数范围3.2-5.1）期间，收缩压降低5毫米汞柱可降低慢性肾脏病（CKD）患者（风险比[HR] 0.91 [95% 置信区间 0.87-0.94]）和非CKD患者（HR 0.90 [95% CI 0.88-0.93]）主要心血管疾病的风险（pinteraction>0.99）。

Furthermore, these observed relative risk reductions were consistent across all CKD stages, including severe stages 4-5 (pinteraction>0·99).

此外，这些观察到的相对风险降低在所有CKD阶段中是一致的，包括严重的4-5期（pinteraction>0.99）。

Similar treatment effects were observed by proteinuria status and across blood-pressure categories, down to <120/70 mm Hg.

通过蛋白尿状态和不同血压类别观察到相似的治疗效果，直至血压降至<120/70毫米汞柱。

However, the relative treatment effect in individuals with CKD was notably attenuated among those with coexisting diabetes (HR 0·96 [95% CI 0·90-1·02]) compared with those without (0·88 [0·84-0·93]; pinteraction=0·044).

然而，与没有糖尿病的患者相比，患有慢性肾脏病（CKD）且伴有糖尿病的患者相对治疗效果显著减弱（HR 0·96 [95% 置信区间 0·90-1·02]），而没有糖尿病的患者为（0·88 [0·84-0·93]；pinteraction=0·044）。

The stratified analysis within each drug class showed that the class-specific effects of antihypertensive agents versus placebo on cardiovascular disease risk remained unchanged across the investigated subgroups.

在每个药物类别内的分层分析显示，抗高血压药物与安慰剂相比对心血管疾病风险的类别特定效应在所研究的亚组中保持不变。

interpretation

In the context of cardiovascular risk reduction, the relative benefit of blood-pressure lowering in patients with CKD is similar to that in individuals without CKD, with consistent efficacy across all CKD stages, blood-pressure thresholds, and proteinuria status.

在心血管风险降低的背景下，慢性肾脏病患者的降压相对益处与无慢性肾脏病的个体相似，且在所有慢性肾脏病阶段、血压阈值和蛋白尿状态下的疗效一致。

However, notably, this relative benefit is attenuated in patients with CKD and concomitant diabetes, underscoring the requirement for adapted therapeutic strategies in this high-risk subgroup.

然而，值得注意的是，这种相对益处在患有慢性肾脏病（CKD）并伴有糖尿病的患者中减弱，强调了在这一高风险亚组中需要适应性治疗策略。

Moreover, the class-specific effects of principal antihypertensives in CKD mirror those observed in the broader population, independent of CKD stage or proteinuria status.

此外，主要降压药物在CKD中的类别特异性效应与在更广泛人群中的观察结果相似，与CKD阶段或蛋白尿状态无关。

funding

British Heart Foundation.

英国心脏基金会。