Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) Study.
Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) Study.
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DOI：
10.1161/circulationaha.114.014536
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发表时间：
2015-05-19
期刊：
影响因子：
37.8
通讯作者：
NHLBI Heart Failure Clinical Research Network
中科院分区：
文献类型：
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作者：
Givertz MM;Anstrom KJ;Redfield MM;Deswal A;Haddad H;Butler J;Tang WH;Dunlap ME;LeWinter MM;Mann DL;Felker GM;O'Connor CM;Goldsmith SR;Ofili EO;Saltzberg MT;Margulies KB;Cappola TP;Konstam MA;Semigran MJ;McNulty SE;Lee KL;Shah MR;Hernandez AF;NHLBI Heart Failure Clinical Research Network
氧化应激可能导致心力衰竭（HF）进展。抑制高尿酸血症HF患者的黄嘌呤氧化酶可改善预后。在一项双盲、多中心试验中，我们将253例有症状的HF、左心室射血分数（LVEF）≤ 40%、血清尿酸水平≥9.5 mg/dL的患者随机分为别嘌呤醇组（目标剂量，每日600 mg）或安慰剂组。24周时的主要复合终点基于生存率、HF恶化和患者总体评估。次要终点包括生活质量、次极量运动能力和LVEF的变化。与安慰剂组相比，别嘌呤醇组的尿酸水平显著降低（治疗差异，第12周和第24周分别为-4.2 [-4.9，-3.5] mg/dL和-3.5 [-4.2，-2.7] mg/dL，P均<0.0001）。第24周时，别嘌呤醇组和安慰剂组患者的临床状态无显著差异（分别为恶化45% vs. 46%，不变42% vs. 34%，改善13% vs. 19%; P=0.68）。在第12周和第24周，两组之间的堪萨斯城心肌病问卷评分或6分钟步行距离的变化无显著差异。在24周时，两组或两组之间的LVEF均未发生变化。别嘌呤醇组皮疹发生率更高（10% vs. 2%，P=0.01），但两组严重不良事件发生率无差异（20% vs. 15%，P=0.36）。在射血分数降低和尿酸水平升高的高危HF患者中，别嘌呤醇抑制黄嘌呤氧化酶未能改善24周时的临床状态、运动能力、生活质量或LVEF。
Oxidative stress may contribute to heart failure (HF) progression. Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes. We randomized 253 patients with symptomatic HF, left ventricular ejection fraction (LVEF) ≤40%, and serum uric acid levels ≥9.5 mg/dL to receive allopurinol (target dose, 600 mg daily) or placebo in a double-blind, multicenter trial. The primary composite endpoint at 24 weeks was based on survival, worsening HF, and patient global assessment. Secondary endpoints included change in quality of life, submaximal exercise capacity, and LVEF. Uric acid levels were significantly reduced with allopurinol compared to placebo (treatment difference, −4.2 [−4.9, −3.5] mg/dL and −3.5 [−4.2, −2.7] mg/dL at 12 and 24 weeks, respectively, both P<0.0001). At 24 weeks, there was no significant difference in clinical status between the allopurinol- and placebo-treated patients (worsened 45% vs. 46%, unchanged 42% vs. 34%, improved 13% vs. 19%, respectively; P=0.68). At 12 and 24 weeks, there was no significant difference in change in Kansas City Cardiomyopathy Questionnaire scores or 6-minute walk distances between the 2 groups. At 24 weeks, LVEF did not change in either group or between groups. Rash occurred more frequently with allopurinol (10% vs. 2%, P=0.01), but there was no difference in serious adverse event rates between the groups (20% vs. 15%, P=0.36). In high-risk HF patients with reduced ejection fraction and elevated uric acid levels, xanthine oxidase inhibition with allopurinol failed to improve clinical status, exercise capacity, quality of life, or LVEF at 24 weeks.