Givertz Michael M, Anstrom Kevin J, Redfield Margaret M, Deswal Anita, Haddad Haissam, Butler Javed, Tang W H Wilson, Dunlap Mark E, LeWinter Martin M, Mann Douglas L, Felker G Michael, O'Connor Christopher M, Goldsmith Steven R, Ofili Elizabeth O, Saltzberg Mitchell T, Margulies Kenneth B, Cappola Thomas P, Konstam Marvin A, Semigran Marc J, McNulty Steven E, Lee Kerry L, Shah Monica R, Hernandez Adrian F
From Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.M.G.); Duke University Medical Center, Durham, NC (K.J.A., G.M.F., C.M.O., S.E.M., K.L.L., A.F.H.); Mayo Clinic, Rochester, MN (M.M.R.); Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX (A.D.); Ottawa Heart Institute, Ontario, Canada (H.H.); Emory University, Atlanta, GA (J.B.); Cleveland Clinic, OH (W.H.W.T.); MetroHealth Campus of Case Western Reserve University, Cleveland, OH (M.E.D.); University of Vermont, Burlington (M.M.L.); Washington University, St. Louis, MO (D.L.M.); Hennepin County Medical Center, Minneapolis, MN (S.R.G.); Morehouse School of Medicine, Atlanta, GA (E.O.O.); Christiana Care Health System, Newark, DE (M.T.S.); University of Pennsylvania, Philadelphia (K.B.M., T.P.C.); Tufts Medical Center, Boston, MA (M.A.K.); Massachusetts General Hospital, Boston (M.J.S.); and National Heart, Lung, and Blood Institute, Bethesda, MD (M.R.S.).
Circulation. 2015 May 19;131(20):1763-71. doi: 10.1161/CIRCULATIONAHA.114.014536. Epub 2015 Apr 14.
Oxidative stress may contribute to heart failure (HF) progression. Inhibiting xanthine oxidase in hyperuricemic HF patients may improve outcomes.
We randomly assigned 253 patients with symptomatic HF, left ventricular ejection fraction ≤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 end point at 24 weeks was based on survival, worsening HF, and patient global assessment. Secondary end points included change in quality of life, submaximal exercise capacity, and left ventricular ejection fraction. Uric acid levels were significantly reduced with allopurinol in comparison with 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% versus 46%, unchanged 42% versus 34%, improved 13% versus 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, left ventricular ejection fraction did not change in either group or between groups. Rash occurred more frequently with allopurinol (10% versus 2%, P=0.01), but there was no difference in serious adverse event rates between the groups (20% versus 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 left ventricular ejection fraction at 24 weeks.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00987415.
氧化应激可能促使心力衰竭（HF）病情进展。抑制高尿酸血症HF患者的黄嘌呤氧化酶可能改善预后。
在一项双盲、多中心试验中，我们将253例有症状的HF患者、左心室射血分数≤40%且血清尿酸水平≥9.5mg/dL的患者随机分配接受别嘌醇（目标剂量，每日600mg）或安慰剂治疗。24周时的主要复合终点基于生存率、HF恶化情况及患者整体评估。次要终点包括生活质量变化、次极量运动能力及左心室射血分数。与安慰剂相比，别嘌醇使尿酸水平显著降低（12周和24周时的治疗差异分别为-4.2[-4.9, -3.5]mg/dL和-3.5[-4.2, -2.7]mg/dL，P均<0.0001）。24周时，别嘌醇治疗组和安慰剂治疗组患者的临床状况无显著差异（病情恶化分别为45%对46%，无变化分别为42%对34%，改善分别为13%对19%；P=0.68）。在12周和24周时，两组间堪萨斯城心肌病问卷评分变化或6分钟步行距离无显著差异。24周时，两组及组间的左心室射血分数均未改变。别嘌醇组皮疹发生率更高（10%对2%，P=0.01），但两组严重不良事件发生率无差异（20%对15%，P=0.36）。
在射血分数降低且尿酸水平升高的高危HF患者中，使用别嘌醇抑制黄嘌呤氧化酶在24周时未能改善临床状况、运动能力、生活质量或左心室射血分数。
