Malhotra Rakesh, Nguyen Hoang Anh, Benavente Oscar, Mete Mihriye, Howard Barbara V, Mant Jonathan, Odden Michelle C, Peralta Carmen A, Cheung Alfred K, Nadkarni Girish N, Coleman Ruth L, Holman Rury R, Zanchetti Alberto, Peters Ruth, Beckett Nigel, Staessen Jan A, Ix Joachim H
Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, La Jolla.
Imperial Valley Family Care Medical Group, El Centro, California.
JAMA Intern Med. 2017 Oct 1;177(10):1498-1505. doi: 10.1001/jamainternmed.2017.4377.
Trials in patients with hypertension have demonstrated that intensive blood pressure (BP) lowering reduces the risk of cardiovascular disease and all-cause mortality but may increase the risk of chronic kidney disease (CKD) incidence and progression. Whether intensive BP lowering is associated with a mortality benefit in patients with prevalent CKD remains unknown.
To conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to investigate if more intensive compared with less intensive BP control is associated with reduced mortality risk in persons with CKD stages 3 to 5.
Ovid MEDLINE, Cochrane Library, EMBASE, PubMed, Science Citation Index, Google Scholar, and clinicaltrials.gov electronic databases.
All RCTs were included that compared 2 defined BP targets (either active BP treatment vs placebo or no treatment, or intensive vs less intensive BP control) and enrolled adults (≥18 years) with CKD stages 3 to 5 (estimated glomerular filtration rate <60 mL/min/1.73 m2) exclusively or that included a CKD subgroup between January 1, 1950, and June 1, 2016.
Two of us independently evaluated study quality and extracted characteristics and mortality events among persons with CKD within the intervention phase for each trial. When outcomes within the CKD group had not previously been published, trial investigators were contacted to request data within the CKD subset of their original trials.
All-cause mortality during the active treatment phase of each trial.
This study identified 30 RCTs that potentially met the inclusion criteria. The CKD subset mortality data were extracted in 18 trials, among which there were 1293 deaths in 15 924 participants with CKD. The mean (SD) baseline systolic BP (SBP) was 148 (16) mm Hg in both the more intensive and less intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the more intensive arm and by 8 mm Hg to 140 mm Hg in the less intensive arm. More intensive vs less intensive BP control resulted in 14.0% lower risk of all-cause mortality (odds ratio, 0.86; 95% CI, 0.76-0.97; P = .01), a finding that was without significant heterogeneity and appeared consistent across multiple subgroups.
Randomization to more intensive BP control is associated with lower mortality risk among trial participants with hypertension and CKD. Further studies are required to define absolute BP targets for maximal benefit and minimal harm.
高血压患者试验表明,强化降压可降低心血管疾病风险和全因死亡率,但可能增加慢性肾脏病(CKD)发病及进展风险。强化降压是否与已患CKD患者的死亡率获益相关尚不清楚。
对随机临床试验(RCT)进行系统评价和荟萃分析,以研究与较低强度血压控制相比,强化血压控制是否与3至5期CKD患者的死亡风险降低相关。
Ovid MEDLINE、Cochrane图书馆、EMBASE、PubMed、科学引文索引、谷歌学术和clinicaltrials.gov电子数据库。
纳入所有比较两个明确血压目标(活性血压治疗与安慰剂或不治疗,或强化与较低强度血压控制)的RCT,且仅纳入3至5期CKD(估计肾小球滤过率<60 mL/min/1.73 m²)的成年人(≥18岁),或纳入1950年1月1日至2016年6月1日期间包含CKD亚组的试验。
我们两人独立评估研究质量,并提取每个试验干预阶段CKD患者的特征和死亡事件。当CKD组的结果此前未发表时,联系试验研究者索取其原始试验CKD亚组的数据。
每个试验活性治疗阶段的全因死亡率。
本研究确定了30项可能符合纳入标准的RCT。18项试验提取了CKD亚组的死亡率数据,其中15924例CKD参与者中有1293例死亡。强化组和较低强度组的平均(标准差)基线收缩压(SBP)均为148(16)mmHg。强化组SBP平均下降16 mmHg至132 mmHg,较低强度组下降8 mmHg至140 mmHg。与较低强度血压控制相比,强化血压控制使全因死亡风险降低14.0%(比值比,0.86;95%CI,0.76 - 0.97;P = 0.01),这一结果无显著异质性,且在多个亚组中似乎一致。
随机分配至强化血压控制与高血压合并CKD试验参与者的较低死亡风险相关。需要进一步研究来确定最大获益和最小伤害的绝对血压目标。