Medical Examination Center, Inagi Municipal Hospital, Tokyo, Japan.
Institute for Health Outcomes and Process Evaluation Research (iHope International), Kyoto, Japan.
Am J Nephrol. 2017;46(6):439-447. doi: 10.1159/000482013. Epub 2017 Nov 21.
Does the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers individually or as a combination confer a survival benefit in hemodialysis patients? The answer to this question is yet unclear.
We performed a case-cohort study using data from the Mineral and Bone Disorder Outcomes Study for Japanese CKD stage 5D patients (MBD-5D), a 3-year multicenter prospective case-cohort study, including 8,229 hemodialysis patients registered from 86 facilities in Japan. All patients had secondary hyperparathyroidism, a condition defined as a parathyroid hormone level ≥180 pg/mL and/or receiving vitamin D receptor activators. We compared all-cause mortality rates between those receiving ACEI, ARB, and their combination and non-users with interaction testing. We used marginal structural Poisson regression (causal model) to estimate the causal effect and interaction adjusted for possible time-dependent confounding. Cardiovascular mortality was also evaluated.
Among 3,762 randomly sampled subcohort patients, those taking ACEI, ARB, and their combination at baseline accounted for 4.0, 31.6, and 3.8%, respectively. Over 3 years, 1,226 all-cause and 462 cardiovascular deaths occurred. Compared to non-users, ARB-alone users had a lower all-cause mortality rate (adjusted incident rate ratio [aIRR] 0.62, 95% CI 0.50-0.76), whereas ACEI-alone users showed a statistically similar rate (aIRR 1.01, 95% CI 0.57-1.77). On the contrary, combination users had a greater mortality rate (aIRR 2.56, 95% CI 1.22-5.37), showing significant interaction (p = 0.03). Analysis for cardiovascular mortality showed similar results.
Among hemodialysis patients with secondary hyperparathyroidism, unlike ACEI use, ARB use was associated with greater survival than non-use. Conversely, combination use was associated with greater mortality. Controlled trials are warranted to verify the causality factors of these associations.
血管紧张素转换酶抑制剂和血管紧张素受体阻滞剂单独或联合使用是否能给血液透析患者带来生存获益？这个问题的答案尚不清楚。
我们使用日本慢性肾脏病 5 期 5D 患者的矿物质和骨代谢紊乱结局研究（MBD-5D）的数据进行了病例对照研究，这是一项为期 3 年的多中心前瞻性病例对照研究，共纳入了来自日本 86 个中心的 8229 名血液透析患者。所有患者均患有继发性甲状旁腺功能亢进症，定义为甲状旁腺激素水平≥180pg/mL 和/或正在接受维生素 D 受体激动剂治疗。我们通过交互检验比较了接受 ACEI、ARB 和联合治疗的患者与未使用者的全因死亡率。我们使用边缘结构泊松回归（因果模型）来估计因果效应，并调整了可能的时变混杂因素的交互作用。还评估了心血管死亡率。
在随机抽取的 3762 名亚队列患者中，基线时接受 ACEI、ARB 和联合治疗的患者分别占 4.0%、31.6%和 3.8%。在 3 年期间，发生了 1226 例全因死亡和 462 例心血管死亡。与未使用者相比，单独使用 ARB 的患者全因死亡率较低（调整后的发病率比[aIRR]0.62，95%CI0.50-0.76），而单独使用 ACEI 的患者死亡率相似（aIRR1.01，95%CI0.57-1.77）。相反，联合用药组死亡率更高（aIRR2.56，95%CI1.22-5.37），且存在显著交互作用（p=0.03）。心血管死亡率分析得到了类似的结果。
在患有继发性甲状旁腺功能亢进症的血液透析患者中，与 ACEI 不同，ARB 的使用与非使用相比与更高的生存率相关。相反，联合使用与更高的死亡率相关。需要进行对照试验来验证这些关联的因果因素。
