Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial.
Cinacalcet, dialysate calcium concentration, and cardiovascular events in the EVOLVE trial.
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DOI：
10.1111/hdi.12382
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发表时间：
2016-07
期刊：
影响因子：
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通讯作者：
Middleton JP
中科院分区：
文献类型：
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作者：
Pun PH;Abdalla S;Block GA;Chertow GM;Correa-Rotter R;Dehmel B;Drüeke TB;Floege J;Goodman WG;Herzog CA;London GM;Mahaffey KW;Moe SM;Parfrey PS;Wheeler DC;Middleton JP
在接受血液透析的患者中，钙调节异常与心血管事件风险增加有关。西那卡塞通过其对甲状旁腺激素分泌的影响降低血清钙浓度，并被假设可降低心血管事件的风险。在观察性队列研究中，低透析液钙浓度处方和观察到的较大血清-透析液钙梯度与透析机构内或透析围透析期心脏骤停的风险较高相关。我们进行了这项研究，以检查在评价盐酸西那卡塞治疗降低心血管事件（EVOLVE）试验的参与者中与透析液钙和血清-透析液梯度相关的风险。在EVOLVE中，3883例血液透析患者以1：1的比例随机接受西那卡塞或安慰剂治疗。透析液钙的给药由主治医生决定。我们检查了基线透析液钙浓度或血清-透析液钙梯度是否改变了西那卡塞对以下裁定终点的影响：1）主要复合终点（死亡或首次非致命性心肌梗死、因不稳定型心绞痛住院、心力衰竭或外周血管事件）; 2）心血管死亡;和3）猝死。在EVOLVE中，与北美相比，欧洲和拉丁美洲使用较高透析液钙浓度的情况更为普遍。西那卡塞组血清钙浓度显著下降;两组透析液钙浓度变化不频繁。基线透析液钙浓度或血清-透析液钙梯度与检查的终点之间无相关性。基线透析液钙和血清-透析液钙梯度均未显著改变西那卡塞对检查结局的影响。西那卡塞对心血管死亡和主要心血管事件的影响不受透析液钙处方和血清-透析液钙梯度的影响。
Among patients receiving hemodialysis, abnormalities in calcium regulation have been linked to an increased risk of cardiovascular events. Cinacalcet lowers serum calcium concentrations through its effect on parathyroid hormone secretion and has been hypothesized to reduce the risk of cardiovascular events. In observational cohort studies, prescriptions of low dialysate calcium concentration and larger observed serum–dialysate calcium gradients have been associated with higher risks of in-dialysis facility or peri-dialytic sudden cardiac arrest. We performed this study to examine risks associated with dialysate calcium and serum-dialysate gradients among participants in the Evaluation of Cinacalcet Hydrochloride Therapy to Lower Cardiovascular Events (EVOLVE) trial. In EVOLVE, 3883 hemodialysis patients were randomized 1:1 to cinacalcet or placebo. Dialysate calcium was administered at the discretion of treating physicians. We examined whether baseline dialysate calcium concentration or the serum–dialysate calcium gradient modified the effect of cinacalcet on the following adjudicated endpoints: 1) primary composite endpoint (death or first non-fatal myocardial infarction, hospitalization for unstable angina, heart failure or peripheral vascular event); 2) cardiovascular death; and 3) sudden death. In EVOLVE, use of higher dialysate calcium concentrations was more prevalent in Europe and Latin America compared to North America. There was a significant fall in serum calcium concentration in the cinacalcet group; dialysate calcium concentrations were changed infrequently in both groups. There was no association between baseline dialysate calcium concentration or serum–dialysate calcium gradient and the endpoints examined. Neither the baseline dialysate calcium nor the serum–dialysate calcium gradient significantly modified the effects of cinacalcet on the outcomes examined. The effects of cinacalcet on cardiovascular death and major cardiovascular events are not altered by the dialysate calcium prescription and serum-dialysate calcium gradient.