华法林对房颤相关AMI的慢性肾病患者有益

《美国医学会杂志》(JAMA)3月4日在线发表的一项瑞典前瞻性全国队列研究显示，在所有严重程度类别的慢性肾病(CKD)患者中，华法林治疗可降低偶发性急性心肌梗死(MI)伴房颤后的死亡、复发性MI和缺血性卒中(复合终点)的发生率。在1年随访期间，华法林在提供该获益的同时并不导致出血风险增加(JAMA 2014 March 4 [doi:10.1001/jama.2014.1334])。 

这项研究由卡罗林斯卡研究所分子医学中心的Juan Jesus Carrero医生及其同事进行，入组24,317例患者。约半数的患者患有3期或3期以上CKD。仅22%在出院时被给予华法林。

随访期间，发生9,002起复合终点事件：3,551起死亡、4,573起复发性MI和878起缺血性卒中。在所有CKD严重程度类别中，使用华法林的患者的死亡、MI和缺血性卒中发生率分别比未使用华法林的患者低5.8%、2.2%和1.8%。然而，华法林组出血事件相对风险并不显著高于非华法林组，不管CKD严重程度如何。

这些研究结果驳斥了一些既往观察性研究的结果，后者显示华法林治疗导致重度CKD患者的死亡或卒中风险增加，进而促使修订治疗指南。具有讽刺意味的是，CKD患者预防性使用华法林的潜在获益最大，因为他们的肾功能不全使其发生卒中和死亡的风险增加。

该研究获瑞典战略研究基金会支持。Carrero医生声明无潜在经济利益冲突。其他研究者声明与多家药企存在联系。

随刊述评：研究结果可能不宜外推

斯坦福大学肾病科的Wolfgang C. Winkelmayer医生和心血管内科的Mintu P. Turakhia医生表示，这项瑞典研究的结果可能不适用于其他国家发生急性MI伴房颤的CKD患者，因为瑞典卫生保健系统提供的INR控制质量优于其他国家，治疗窗内时间(time in therapeutic range，TTR)为77%。相比之下，美国的平均TTR仅为66%，并且该国在44个参加一项大型国际研究的国家中排名第16位。另一项研究显示，在具有抗凝诊所网络的美国卫生保健系统中，在使用华法林的最初6个月内，平均TTR仅为48%，此后为61%。

除非瑞典卫生保健系统达到的优异INR控制质量可被复制，否则华法林的获益可能会明显降低并可能造成伤害。开展进一步研究以定义CKD患者中的净临床获益的TTR阈值，对于治疗实践具有关键意义。

Winkelmayer医生是JAMA的副主编，并且是Acumen等多家公司的顾问。Turakhia医生与吉利德科学公司等多家公司存在联系(JAMA 2014;311:913-4)。

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By: MARY ANN MOON, Cardiology News Digital Network

Warfarin therapy decreased the composite endpoint of death, recurrent myocardial infarction, and ischemic stroke after an incident acute MI with atrial fibrillation among patients who had chronic kidney disease of all severities, according to a report published online March 4 in JAMA.

In a prospective nationwide cohort study involving 24,317 such patients in Sweden, warfarin provided this benefit without raising the risk of bleeding during 1 year of follow-up. Approximately half of the study participants had CKD of stage 3 or higher. Only 22% were given warfarin at hospital discharge, said Juan Jesus Carrero, Ph.D., of the Center for Molecular Medicine, Karolinska Institutet, Stockholm, and his associates.

During follow-up, there were 9,002 composite endpoint events: 3,551 deaths, 4,573 recurrent MIs, and 878 ischemic strokes. Across all categories of CKD severity, patients taking warfarin had 5.8% fewer deaths, 2.2% fewer MIs, and 1.8% fewer ischemic strokes than those not taking warfarin. Yet the relative risk of bleeding events was not significantly higher with warfarin, regardless of the severity of CKD, the investigators said (JAMA 2014 March 4 [doi:10.1001/jama.2014.1334]).

These findings refute the results of some earlier observational studies in which warfarin therapy raised the risk of death or stroke in severe CKD, which prompted a modification of treatment guidelines. Ironically, patients with CKD potentially have the most to gain from using prophylactic warfarin, since their renal dysfunction puts them at additional risk of stroke and death, Dr. Carrero and his colleagues noted.

This study was supported by the Swedish Foundation for Strategic Research. Dr. Carrero reported no potential financial conflicts of interest; his associates reported ties to numerous industry sources.

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Findings may not apply elsewhere

The findings by Carrero and colleagues may not apply to patients with CKD who develop acute MI with atrial fibrillation if they don’t have the distinct advantage of residing in Sweden, a country in which the health care system provides better quality of INR control than any other – with a TTR (time in therapeutic range) of 77%, said Dr. Wolfgang C. Winkelmayer and Dr. Mintu P. Turakhia.

In contrast, the mean TTR in the United States was only 66%, and this country ranked 16th out of 44 countries participating in a large international study. Another study showed that mean TTR in U.S. health care systems with anticoagulation clinic networks was only 48% in the first 6 months of warfarin use and 61% thereafter, they noted.

"Unless the excellent quality of INR control achieved by the Swedish Health Care system can be replicated, the benefit of warfarin is likely to be markedly attenuated and possibly could cause harm. Future work that defines the TTR threshold of net clinical benefit in CKD will be critical to inform practice," they said.

Dr. Winkelmayer is in the division of nephrology and the department of health research and policy at Stanford University, Palo Alto, Calif. He is an associate editor at JAMA. Dr. Turakhia is in the division of cardiovascular medicine at Stanford and the Veterans Affairs Palo Alto Health Care System. Dr. Winkelmayer reported serving as an adviser or consultant to Acumen, Amgen, GlaxoSmithKline, Keryx, Medgenics, Medtronic, and Mitsubishi Tanabe; Dr. Turakhia reported ties to Gilead Sciences, iRhythm, Medtronic, Precision Health Economics, and St. Jude Medical. These remarks were taken from their editorial accompanying Dr. Carrero’s report (JAMA 2014;311:913-4).