JAMA：新型药物或可有效降低高钾血症相关的致死性心律失常风险

  近日，刊登在JAMA上的研究论文中，来自圣路加中美心血管学院(Saint Luke's Mid America Heart and Vascular Institute)的研究人员评估了药物锆环硅酸盐治疗高钾血症患者的有效性及安全性。
  高钾血症是一种常见的电解质紊乱障碍，其会引发患者出现潜在的危及生命的心律失常，而且同慢性肾脏疾病、心力衰竭及糖尿病直接相关，目前针对高钾血症患者并没有有效的疗法。锆环硅酸盐是一种可以“诱骗”机体肠道中钾的制剂，此前研究中，这种锆环硅酸盐可以在服用48小时内降低机体的钾水平，而本文研究中研究者评估了服用该制剂后28里机体的一些表现。
  在3期临床阶段，研究者首先在开放性研究的前48小时对258名高钾血症病人进行每日三次的锆环硅酸盐治疗，其中237名患者机体的钾水平恢复到了正常状态，这些患者又随即服用锆环硅酸盐，其中45名患者以5g的量服用，51名患者以10g量服用，56名患者以15g服用，最后85名患者以安慰剂服用治疗，患者连续进行28天药物的服用。
  结果显示，锆环硅酸盐不仅可以使得患者机体的钾水平恢复至正常水平，还可以使得不同程度高钾血症患者机体正常的钾水平保持长达4周；这种降钾水平在所有的病人亚群中都是一致的，锆环硅酸盐服用后24小时内84%病人的机体钾水平都会恢复正常，而在疗法起初的48小时内98%的患者钾水平都会恢复正常。相比安慰剂组来讲，三种不同治疗剂量的锆环硅酸盐均可以使得大部分高钾血症患者机体的钾水平恢复正常，而且可以维持长达28天。
  研究者Bradley S. Dixon表示，未来还需要更多的研究来评估锆环硅酸盐进行长期治疗的安全性和有效性；而以锆环硅酸盐开发的疗法或许是一种治疗轻度高钾血症的有效疗法。（转化医学网360zhyx.com）
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转化医学网推荐的原文摘要：

Zirconium Cyclosilicate for Treatment of Hyperkalemia
JAMA     doi:10.1001/jama.2014.15736
Bradley S. Dixon, MD1,2
Hyperkalemia is a commonly encountered clinical problem and has been reported in up to 10% of hospitalized patients, with 10% to 38% of those episodes associated with medications that block the renin-angiotensin-aldosterone system (RAAS).1 Mortality has been shown to be increased in patients with hyperkalemia even after accounting for other comorbidities.2

Effect of Sodium Zirconium Cyclosilicate on Potassium Lowering for 28 Days Among Outpatients With Hyperkalemia
The HARMONIZE Randomized Clinical Trial
JAMA          doi:10.1001/jama.2014.15688
Mikhail Kosiborod, MD1,2; Henrik S. Rasmussen, MD, PhD3; Philip Lavin, PhD4; Wajeh Y. Qunibi, MD5; Bruce Spinowitz, MD6; David Packham, MD7; Simon D. Roger, MD8; Alex Yang, MD9; Edgar Lerma, MD10,11; Bhupinder Singh, MD3
Importance  Hyperkalemia is a common electrolyte abnormality that may be difficult to manage because of a lack of effective therapies. Sodium zirconium cyclosilicate is a nonabsorbed cation exchanger that selectively binds potassium in the intestine.
Objective  To evaluate the efficacy and safety of zirconium cyclosilicate for 28 days in patients with hyperkalemia.
Design, Setting, and Participants  HARMONIZE was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating zirconium cyclosilicate in outpatients with hyperkalemia (serum potassium ≥5.1 mEq/L) recruited from 44 sites in the United States, Australia, and South Africa (March-August 2014).
Interventions  Patients (n = 258) received 10 g of zirconium cyclosilicate 3 times daily in the initial 48-hour open-label phase. Patients (n = 237) achieving normokalemia (3.5-5.0 mEq/L) were then randomized to receive zirconium cyclosilicate, 5 g (n = 45 patients), 10 g (n = 51), or 15 g (n = 56), or placebo (n = 85) daily for 28 days.
Main Outcomes and Measures  The primary end point was mean serum potassium level in each zirconium cyclosilicate group vs placebo during days 8-29 of the randomized phase.
Results  In the open-label phase, serum potassium levels declined from 5.6 mEq/L at baseline to 4.5 mEq/L at 48 hours. Median time to normalization was 2.2 hours, with 84% of patients (95% CI, 79%-88%) achieving normokalemia by 24 hours and 98% (95% CI, 96%-99%) by 48 hours. In the randomized phase, serum potassium was significantly lower during days 8-29 with all 3 zirconium cyclosilicate doses vs placebo (4.8 mEq/L [95% CI, 4.6-4.9], 4.5 mEq/L [95% CI, 4.4-4.6], and 4.4 mEq/L [95% CI, 4.3-4.5] for 5 g, 10 g, and 15 g; 5.1 mEq/L [95% CI, 5.0-5.2] for placebo; P < .001 for all comparisons). The proportion of patients with mean potassium <5.1 mEq/L during days 8-29 was significantly higher in all zirconium cyclosilicate groups vs placebo (36/45 [80%], 45/50 [90%], and 51/54 [94%] for the 5-g, 10-g, and 15-g groups, vs 38/82 [46%] with placebo; P < .001 for each dose vs placebo). Adverse events were comparable between zirconium cyclosilicate and placebo, although edema was more common in the 15-g group (edema incidence: 2/85 [2%], 1/45 [2%], 3/51 [6%], and 8/56 [14%] patients in the placebo, 5-g, 10-g, and 15-g groups). Hypokalemia developed in 5/51 (10%) and 6/56 patients (11%) in the 10-g and 15-g zirconium cyclosilicate groups, vs none in the 5-g or placebo groups.
Conclusions and Relevance  Among outpatients with hyperkalemia, open-label sodium zirconium cyclosilicate reduced serum potassium to normal levels within 48 hours; compared with placebo, all 3 doses of zirconium cyclosilicate resulted in lower potassium levels and a higher proportion of patients with normal potassium levels for up to 28 days. Further studies are needed to evaluate the efficacy and safety of zirconium cyclosilicate beyond 4 weeks and to assess long-term clinical outcomes.
Trial Registration  clinicaltrials.gov Identifier: NCT02088073