Rolofylline, an Adenosine A(sub 1)-Receptor Antagonist, in Acute Heart Failure.
Rolofylline, an Adenosine A(sub 1)-Receptor Antagonist, in Acute Heart Failure.
复制标题
DOI：
10.1056/nejmoa0912613
复制
发表时间：
2010-10-07
影响因子：
158.5
通讯作者：
Dittrich, Howard C.
中科院分区：
文献类型：
--
作者：
Massie, Barry M.;O'Connor, Christopher M.;Dittrich, Howard C.
背景：肾功能恶化，这是与不良后果，往往发生在急性心力衰竭患者。实验和临床研究表明，可能涉及腺苷介导的反调节反应。我们测试的假设，即使用rolofylline，腺苷A（分1）受体拮抗剂，将改善呼吸困难，降低肾功能恶化的风险，并导致更有利的临床病程在急性heartful.Methods：我们进行了一项多中心，双盲，安慰剂对照试验，涉及急性心力衰竭与肾功能受损住院患者。在24小时内，2033例患者被随机分配，以2：1的比例，每天静脉注射罗洛茶碱（30 mg）或安慰剂，最多3天。主要终点是治疗成功、治疗失败或患者临床状况无变化;该终点根据生存率、心力衰竭状态和肾功能变化定义。次要终点是治疗后发展的持续性肾功能损害和60天的死亡率或再入院的心血管或肾脏causes.Results：罗洛茶碱，与安慰剂相比，没有提供一个好处的主要终点（优势比，0.92; 95%可信区间，0.78至1.09; P=0.35）。持续性肾损害发生率在罗洛茶碱组为15.0%，安慰剂组为13.7%（P=0.44）。到60天，罗洛茶碱组和安慰剂组患者因心血管或肾脏原因死亡或再入院的比例相似（分别为30.7%和31.9%; P=0.86）。不良事件发生率总体相似，但是，只有在rolofylline组的患者有癫痫发作，一个已知的潜在不良反应的A（1分）-受体拮抗剂conclusions：Rolofylline没有一个有利的影响方面的主要临床复合终点，也没有改善肾功能或60天的结果。在急性心力衰竭伴肾功能不全的治疗中没有显示出希望。（由默克的子公司NovaCardia资助; ClinicalTrials.gov编号，NCT 00328692和NCT 00354458。新英格兰医学杂志2010;363：1419-28。
Background: Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A(sub 1)-receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure.Methods: We conducted a multicenter, double-blind, placebo-controlled trial involving patients hospitalized for acute heart failure with impaired renal function. Within 24 hours after presentation, 2033 patients were randomly assigned, in a 2:1 ratio, to receive daily intravenous rolofylline (30 mg) or placebo for up to 3 days. The primary end point was treatment success, treatment failure, or no change in the patient's clinical condition; this end point was defined according to survival, heart-failure status, and changes in renal function. Secondary end points were the post-treatment development of persistent renal impairment and the 60-day rate of death or readmission for cardiovascular or renal causes.Results: Rolofylline, as compared with placebo, did not provide a benefit with respect to the primary end point (odds ratio, 0.92; 95% confidence interval, 0.78 to 1.09; P=0.35). Persistent renal impairment developed in 15.0% of patients in the rolofylline group and in 13.7% of patients in the placebo group (P=0.44). By 60 days, death or readmission for cardiovascular or renal causes had occurred in similar proportions of patients assigned to rolofylline and placebo (30.7% and 31.9%, respectively; P=0.86). Adverse-event rates were similar overall; however, only patients in the rolofylline group had seizures, a known potential adverse effect of A(sub 1)-receptor antagonists.Conclusions: Rolofylline did not have a favorable effect with respect to the primary clinical composite end point, nor did it improve renal function or 60-day outcomes. It does not show promise in the treatment of acute heart failure with renal dysfunction. (Funded by NovaCardia, a subsidiary of Merck; ClinicalTrials.gov numbers, NCT00328692 and NCT00354458.)N Engl J Med 2010;363:1419-28.