Cardiovascular and renal safety outcomes of hypoxia-inducible factor prolyl-hydroxylase inhibitor roxadustat for anemia patients with chronic kidney disease: a systematic review and meta-analysis

This systematic review and meta-analysis were conducted to evaluate the cardiac and kidney-related adverse effects of roxadustat for the treatment of anemia in CKD patients. 18 trials with a total of 8806 participants were identified for analysis. We employed a fixed-effects model for analysis. The pooled result revealed no significant difference in the risk of occurrence of cardiac disorders when comparing CKD patients receiving roxadustat with the placebo (RR = 1.049; CI [0.918 to 1.200]) or ESA (RR = 1.066; CI [0.919 to 1.235]), in both dialysis-dependent (DD) (RR = 1.094; CI [0.925 to 1.293]) or non-dialysis-dependent (NDD) (RR = 1.036; CI [0.916 to 1.171]) CKD patients. No significant difference was observed in the risk of kidney-related adverse events when comparing roxadustat with the placebo (RR = 1.088; CI [0.980 to 1.209]) or ESA (RR = 0.968; CI [0.831 to 1.152]), in DD (RR = 2.649; CI [0.201 to 34.981]) or NDD (RR = 1.053; CI [0.965 to 1.149]) CKD patients. A high risk of hyperkalemia was observed in the roxadustat group in DD (RR = 0.939; CI [0.898 to 0.981]). Incidence of hypertension was higher in the roxadustat for NDD patients (RR = 1.198; CI [1.042 to 1.377]), or compared to the placebo (RR = 1.374; CI [1.153 to 1.638]). In summary, the risk of cardiac or kidney-related events observed in the roxadustat was not significantly increase whether in DD or NDD patients. However, attention must be paid to the occurrence of hyperkalemia for DD patients and hypertension in NDD patients using roxadustat.

本系统评价与Meta分析旨在评估罗沙司他（roxadustat）治疗慢性肾脏病（CKD, Chronic Kidney Disease）患者贫血时的心脏及肾脏相关不良反应。研究最终纳入18项试验，共计8806名受试者用于分析。本研究采用固定效应模型开展统计分析。合并分析结果显示：与安慰剂或促红细胞生成素类药物（ESA, Erythropoiesis-Stimulating Agents）相比，接受罗沙司他治疗的CKD患者发生心脏疾病的风险无显著差异——与安慰剂组比较的相对风险（RR, Relative Risk）为1.049，置信区间（CI, Confidence Interval）为[0.918, 1.200]；与ESA组比较的RR为1.066，CI为[0.919, 1.235]。该结果在依赖透析（DD）亚组（RR=1.094，CI=[0.925, 1.293]）与非依赖透析（NDD）亚组（RR=1.036，CI=[0.916, 1.171]）中均一致。在肾脏相关不良事件方面，罗沙司他组与安慰剂组（RR=1.088，CI=[0.980, 1.209]）或ESA组（RR=0.968，CI=[0.831, 1.152]）的不良事件风险无显著差异；该结果在DD亚组（RR=2.649，CI=[0.201, 34.981]）与NDD亚组（RR=1.053，CI=[0.965, 1.149]）中亦无统计学意义。在依赖透析亚组中，罗沙司他组的高钾血症（hyperkalemia）风险存在统计学关联（RR=0.939；CI=[0.898, 0.981]）。非依赖透析患者使用罗沙司他时，高血压（hypertension）发生率更高：相较于该亚组自身对照的RR为1.198，CI=[1.042, 1.377]；相较于安慰剂组的RR为1.374，CI=[1.153, 1.638]。综上，无论在依赖透析还是非依赖透析的CKD患者中，罗沙司他相关的心脏或肾脏不良事件风险均无显著升高。但临床应用罗沙司他时，需警惕依赖透析患者的高钾血症，以及非依赖透析患者的高血压发生风险。