Department of Renal Medicine, Wollongong Hospital, Wollongong, NSW, Australia.
Renal and Metabolic Division, The George Institute for Global Health, University of New South Wales Medicine & Health, Sydney.
NEJM Evid. 2024 Sep;3(9):EVIDoa2300189. doi: 10.1056/EVIDoa2300189. Epub 2024 Aug 26.
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.
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.
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.
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.).
缺氧诱导因子（HIF）脯氨酰羟化酶抑制剂是一种治疗慢性肾脏病（CKD）贫血的口服药物。在本次系统评价和荟萃分析中，我们评估了 HIF 脯氨酰羟化酶抑制剂的长期安全性。
我们检索了 MEDLINE、Embase 和 Cochrane 数据库，以评估比较 HIF 脯氨酰羟化酶抑制剂与促红细胞生成素刺激剂（ESA）或安慰剂、随访时间大于或等于 48 周的随机试验。主要终点是主要不良心血管事件（MACE），定义为全因死亡、心肌梗死或卒中的复合终点。采用随机效应模型对治疗效果进行汇总。
共纳入 25 项试验，涉及 26478 名参与者。其中，13 项试验纳入了 13230 名透析依赖性 CKD 患者，12 项试验纳入了 13248 名非透析依赖性 CKD 患者。在透析依赖性 CKD 患者（风险比，0.99；95%置信区间[CI]，0.92 至 1.08）和非透析依赖性 CKD 患者（风险比，1.08；95%CI，0.95 至 1.22）中，HIF 脯氨酰羟化酶抑制剂和 ESA 对 MACE 的影响无差异。同样，在非透析依赖性 CKD 患者中，HIF 脯氨酰羟化酶抑制剂和安慰剂对 MACE（风险比，1.10；95%CI，0.96 至 1.27）的影响也无差异。在非透析依赖性 CKD 患者中，HIF 脯氨酰羟化酶抑制剂和 ESA 或安慰剂在 MACE 及心血管死亡的各个组成部分的差异均无统计学意义。在透析依赖性 CKD 中，HIF 脯氨酰羟化酶抑制剂的安全性与 ESA 相当。在非透析依赖性 CKD 中，在安慰剂对照试验中，与 HIF 脯氨酰羟化酶抑制剂相比，ESA 对照试验中透析通路血栓形成、静脉血栓栓塞、感染和高钾血症更为常见。
在透析依赖性 CKD 和非透析依赖性 CKD 成人中，HIF 脯氨酰羟化酶抑制剂与 ESA 的长期心血管安全性无差异。（PROSPERO 注册号，CRD42021278011。）
