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JAMA Intern Med:多学科讨论:强化降压能降低晚期慢性肾病患者死亡风险?

2017-10-27 何娜 环球医学

慢性肾病(CKD)是重大的公共卫生问题,影响全球约两亿人。2017年10月,发表在《JAMA Intern Med》的一项由美国、加拿大、意大利等国科学家进行的系统回顾和荟萃分析,比较了更强化和较低强度降压与3~5期CKD患者死亡风险之间的相关性。请看本期多学科讨论组临床药师各抒己见为您梳理本文看点——

慢性肾病(CKD)是重大的公共卫生问题,影响全球约两亿人。2017年10月,发表在《JAMA Intern Med》的一项由美国、加拿大、意大利等国科学家进行的系统回顾和荟萃分析,比较了更强化和较低强度降压与3~5期CKD患者死亡风险之间的相关性。请看本期多学科讨论组临床药师各抒己见为您梳理本文看点——

重要性高血压患者中进行的试验已经证实,强化降压会降低心血管疾病和全因死亡风险,但是会增加CKD的发生和进展风险。强化降压是否与CKD患者死亡获益相关是未知的。

目的:旨在进行一项随机临床试验的系统评价和荟萃分析,从而调查更强化vs较低强度血压控制是否与3~5期CKD患者死亡风险的降低相关。

数据来源:Ovid Medline、Cochrane图书馆、Embase、Pubmed、科学引文索引、Google学术、clinicaltrials.gov电子数据库。

研究选择:1950年1月1日~2016年6月1日,所有比较2个预先定义的血压目标(积极血压治疗vs安慰剂或不治疗,或更强化vs较低强度血压控制)并仅入组了成年(≥18岁)3~5期CKD(估计肾小球滤过率<60mL/min/1.73m2)患者或纳入了CKD亚组的随机临床试验。

数据采集和分析:两名研究者独立评估了研究质量并提取了每项试验干预期内的CKD患者的特征和死亡事件。当CKD组内的结局还没有进行过发表时,研究者与试验研究者进行沟通,请求他们提供原始试验的CKD亚组内的数据。

主要结局和测量:每项试验积极治疗阶段的全因死亡率。

结果:本研究鉴别出潜在符合入组标准的30项随机临床试验。CKD亚组的死亡数据在18项试验中提取,共有15924例CKD患者,发生了1293例死亡。两组基线的平均(SD)收缩压为148(16)mmHg。更强化组的平均收缩压降至132mmHg,降低了16mmHg,较低强化组降至140mmHg,降低了8mmHg。更强化vs较低强化的血压控制造成了全因死亡风险降低14.0%(比值比OR,0.86;95% CI,0.76~0.97;P=0.01),该结果在各亚组中无显着的异质性,并表现一致。

结论和意义
:在高血压合并CKD的试验患者中,随机分组到更强化血压控制组与较低的死亡风险相关。将来的研究需要定义绝对血压目标,从而使获益最大化,伤害最小化。

请看本期多学科讨论组临床药师各抒己见为您梳理本文看点——

在18项RCTs的系统评价和荟萃分析中,15924名患高血压且eGFR<60 mL/min/1.73 m2的参与者被随机分配到更强化vs较低强化降压组,更强化降压组的患者的全因死亡风险低14.0%。观察到达到两个治疗组之间SBP最大差异的研究中的死亡获益(P=0.06)。这些结果增加了或改善公共卫生政策、临床指南制定和CKD患者个体患者治疗的证据。

之前的Meta分析显示CKD患者强化降压可以降低心血管疾病的发生风险(26项研究,包含30925名参与者,HR 0.83;95% CI,0.76~0.90);心血管疾病这一结局指标很重要,是CKD患者的主要死亡原因之一,但死亡率的结局指标可以综合考虑多个临床结局,是“硬”终点,如可以平衡心血管获益和可能造成AKI和CKD进展的风险。这一研究得到死亡率降低14%与其他纳入所有患者强化降压降低死亡率的风险相似(9~11%),这提示我们强化降压对死亡风险的降低与患者是否合并CKD可能无关。

本研究存在一些局限性。首先,尽管尽了相当大的努力联系研究者,仍无法获得几项既往临床试验中CKD患者的死亡数据。因此,不得已排除了这些试验。18项共纳入约16000名CKD参与者的研究中,未发现异质性证据。尽管不确定,但此发现提供了信心——若将排除的研究纳入所得的结果是相似的。第二,缺乏CKD严重程度的数据,因此不能评估经CKD严重程度分层,更强化降压对死亡率的影响。纳入的试验的大多数个体为CKD 3期,研究者承认,更强化降压的风险和获益可能在更晚期CKD患者中存在差异。第三,单个试验之间,随机治疗组的基线BP和BP下降强度存在差异。同样,研究者不能提供CKD患者中最佳BP目标的估计值。研究者确认,CVD事件、CKD进展、AKI和ESRD可能是更强化降压和死亡率之间因果通路中的重要因素,无法评估这些终点。

专家点评:JNC8指南中推荐对于慢性肾功能不全的患者降压目标值为140/90mmHg,我国2014年高血压基层管理指南提到一般高血压患者降至140/90mmHg以下,慢性肾脏疾病患者的血压目标可以低一些。

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  8. 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    2017-10-27 明天会更好!

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