抗痛风老药或可治疗心脏病

旧金山——在美国心脏病学会(ACC)2013年会上报告的2项研究结果显示，抗高尿酸血症老药别嘌呤醇有望用于2种新的心血管适应证：预防心衰患者房颤和减少2型糖尿病患者左室肥大。

迈阿密大学的Fernando E. Hernandez博士报告称，别嘌呤醇是一种黄嘌呤氧化酶抑制剂，用于抗痛风治疗。该药物可能用于减少心衰患者房颤发生率的依据是，血清尿酸已经成为心衰患者死亡的独立标志物和新发房颤的预测因素。黄嘌呤氧化酶不仅是对心肌功能有不良影响的活性氧的来源，而且还是黄嘌呤转化为尿酸的催化剂。

在Hernandez博士报告的这项队列研究中，共纳入603例迈阿密退伍军人事务部心衰医院住院患者，其中103例患者服用别嘌呤醇，500例未使用别嘌呤醇，两组患者的年龄、冠心病发病率、中位左室射血分数、左心房大小等基线特征匹配良好，并按照指南建议使用ACE抑制剂和β受体阻滞剂。

结果显示，在长达5年的随访期间，别嘌呤组和对照组患者新发房颤率分别为184例/1,000(人·年)和252例/1,000(人·年)。校正潜在混淆因素细微差异后的Cox比例风险分析显示，服用别嘌呤醇与房颤风险降低47%呈独立相关(P=0.04)。但研究者强调，这一令人兴奋的结果尚需前瞻性随机试验加以证实。

苏格兰邓迪大学的Benjamin R. Szwejkowski博士在另外一项报告中指出，左室肥大(LVH)常见于2型糖尿病患者，是导致心血管就疾病发病率和死亡率增加的原因。鉴于LVH在一定程度上可能与氧化应激相关，而别嘌呤醇可抑制黄嘌呤氧化酶减少氧化应激，有可能导致LVH消退，研究者开展了一项随机、双盲、安慰剂对照临床试验，入组66例超声心动图显示伴有LVH的2型糖尿病患者，随机给予600 mg/d别嘌呤醇或安慰剂治疗，共治疗9个月。主要终点指标为心脏MRI 检测的9个月左心室重量变化。

结果显示，别嘌呤组左心室重量下降明显，平均减少2.65g，而对照组增加1.21g。同样，别嘌呤醇组平均左室重量指数显著下降1.32 g/m2 ，而对照组增加0.65 g/m2 。但两组患者血流介导的舒张功能在随访期间均未见明显变化。研究者认为，别嘌呤醇或许可有效减少伴有LVH的2型糖尿病患者的心血管风险。

Szwejkowski 博士和Hernandez博士均报告无相关利益冲突。

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By: BRUCE JANCIN, Cardiology News Digital Network

SAN FRANCISCO – The venerable antihyperuricemic agent allopurinol has shown early promise for two novel cardiovascular applications: prevention of atrial fibrillation in the setting of heart failure and reduction of left ventricular hypertrophy in patients with type 2 diabetes.

Allopurinol is a xanthine oxidase inhibitor and antigout drug. The rationale for the drug’s use in reducing the incidence of atrial fibrillation in patients with heart failure lies in the observation that serum uric acid has emerged as an independent marker of mortality and a predictor of new-onset atrial fibrillation in heart failure. Xanthine oxidase is not only a source of reactive oxygen species that adversely affect myocardial function, but it also catalyzes the conversion of xanthine to uric acid, Dr. Fernando E. Hernandez explained at the annual meeting of the American College of Cardiology.

He presented a retrospective cohort study involving 603 patients enrolled in the Miami Veterans Affairs heart failure clinic. The 103 on allopurinol, and the 500 who were not, matched up well in terms of baseline characteristics including age, prevalence of coronary artery disease, median left ventricular ejection, left atrial size, and use of guideline-recommended ACE inhibitors and beta-blockers.

During up to 5 years of follow-up, the incidence of new-onset atrial fibrillation was 184 cases/1,000 person-years in the allopurinol users compared with 252/1,000 person-years in controls. In a Cox proportional hazards analysis adjusted for small differences in potential confounders, the use of allopurinol was independently associated with a 47% reduction in the risk of atrial fibrillation (P = .04), reported Dr. Hernandez of the University of Miami.

This intriguing finding needs to be confirmed in randomized prospective trials, he noted.

In a separate presentation, Dr. Benjamin R. Szwejkowski noted that left ventricular hypertrophy (LVH) is common in patients with type 2 diabetes and contributes to their elevated risk of cardiovascular morbidity and mortality.

Based on their hypothesis that LVH is related in part to oxidative stress and reducing that stress via xanthine oxidase inhibition using allopurinol can cause LVH regression, the investigators conducted a randomized, double-blind placebo-controlled clinical trial. Sixty-six patients with type 2 diabetes and echocardiographic evidence of LVH were randomized to allopurinol at 600 mg/day or placebo for 9 months.

The primary study endpoint was change in left ventricular mass between baseline and 9 months, as measured by cardiac MRI. Allopurinol resulted in a significant mean 2.65-g reduction in LV mass, while in the control group LV mass increased by 1.21 g. Similarly, LV mass indexed to body surface area fell significantly by 1.32 g/m2 in the allopurinol group while increasing by 0.65 g/m2 in the placebo arm, reported Dr. Szwejkowski of the University of Dundee(Scotland).

"Allopurinol may be a useful therapy to reduce cardiovascular risk in type 2 diabetic patients with LVH," according to the cardiologist.

Flow-mediated dilatation didn’t change significantly over time in either study group.

Dr. Szwejkowski and Dr. Hernandez reported having no relevant financial conflicts.