背景:缺氧诱导因子(HIF)脯氨酸酰羟化酶抑制剂是一种口服治疗慢性肾脏病(CKD)贫血的药物。在这篇系统综述和荟萃分析中,我们评估了HIF丙基羟化酶抑制剂的长期安全性.
方法:我们搜索了MEDLINE,Embase,和Cochrane数据库,用于比较HIF丙基羟化酶抑制剂与红细胞生成刺激剂(ESA)或安慰剂的随机试验,随访时间大于或等于48周。主要结局是主要不良心血管事件(MACE),定义为全因死亡的复合物,心肌梗塞,或中风。使用随机效应模型汇集治疗效应。
结果:纳入了25项试验,涉及26,478名参与者。其中,13项试验招募了13,230名透析依赖性CKD参与者,12项试验纳入了13,248名非透析依赖性CKD参与者。没有证据表明HIF丙基羟化酶抑制剂和ESA对透析依赖性CKD患者的MACE有不同的影响(风险比,0.99;95%置信区间[CI],0.92至1.08)或患有非透析依赖性CKD的人(风险比,1.08;95%CI,0.95至1.22)。同样,没有证据表明HIF丙基羟化酶抑制剂和安慰剂对MACE有不同的影响(风险比,1.10;95%CI,0.96至1.27)在非透析依赖性CKD患者中。对于MACE和心血管死亡的单个组分,观察到HIF丙基羟化酶抑制剂与ESA或安慰剂之间缺乏差异。在透析依赖性CKD中,HIF脯氨酸酰羟化酶抑制剂对其他结果的安全性与ESA相当。在非透析依赖性CKD中,透析通路血栓形成,静脉血栓栓塞,感染,在安慰剂对照试验中,使用HIF脯氨酸酰羟化酶抑制剂时发生高钾血症的频率更高,但在ESA对照试验中没有发生.
结论:没有证据表明在透析依赖性CKD成人和非透析依赖性CKD成人中,HIF脯氨酸酰羟化酶抑制剂和ESA的长期心血管安全性存在差异。(PROSPERO注册号,CRD42021278011。).
BACKGROUND: Hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitors are an oral treatment for anemia of chronic kidney disease (CKD). In this systematic review and meta-analysis, we assessed long-term safety of HIF prolyl hydroxylase inhibitors.
METHODS: We searched MEDLINE, Embase, and Cochrane databases for randomized trials comparing HIF prolyl hydroxylase inhibitors with an erythropoiesis-stimulating agent (ESA) or placebo with greater than or equal to 48 weeks of follow-up. The primary outcome was major adverse cardiovascular event (MACE), defined as a composite of all-cause death, myocardial infarction, or stroke. Treatment effects were pooled using random-effects models.
RESULTS: Twenty-five trials involving 26,478 participants were included. Of these, 13 trials enrolled 13,230 participants with dialysis-dependent CKD, and 12 trials enrolled 13,248 participants with nondialysis-dependent CKD. There was no evidence that HIF prolyl hydroxylase inhibitors and ESA had different effects on MACE in people with dialysis-dependent CKD (risk ratio, 0.99; 95% confidence interval [CI], 0.92 to 1.08) or people with nondialysis-dependent CKD (risk ratio, 1.08; 95% CI, 0.95 to 1.22). Similarly, there was no evidence that HIF prolyl hydroxylase inhibitors and placebo had different effects on MACE (risk ratio, 1.10; 95% CI, 0.96 to 1.27) in people with nondialysis-dependent CKD. The lack of difference between HIF prolyl hydroxylase inhibitors and ESA or placebo was observed for individual components of MACE and cardiovascular death. Safety of HIF prolyl hydroxylase inhibitors for other outcomes was comparable with ESA in dialysis-dependent CKD. In nondialysis-dependent CKD, dialysis access thrombosis, venous thromboembolism, infections, and hyperkalemia occurred more frequently with HIF prolyl hydroxylase inhibitors in placebo-controlled trials but not in ESA-controlled trials.
CONCLUSIONS: There was no evidence of a difference in the long-term cardiovascular safety profile of HIF prolyl hydroxylase inhibitors and ESA in adults with dialysis-dependent CKD and adults with nondialysis-dependent CKD. (PROSPERO registration number, CRD42021278011.).