中国科技论文统计源期刊 中文核心期刊  
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《乌利希期刊指南》
WHO《西太平洋地区医学索引》来源期刊  
日本科学技术振兴机构数据库(JST)
第七届湖北十大名刊提名奖  
HERALD OF MEDICINE, 2018, 37(5): 559-562
doi: 10.3870/j.issn.1004-0781.2018.05.012
达比加群酯与华法林对扩张型心肌病患者的抗凝疗效比较*
Comparison of Anticoagulant Treatment Effect Between Dabigatran Etexilate and Warfarin in Patients with Dilated Cardiomyopathy
武丽萍1, 胡立禄1,, 杜鹃2, 贾国渠1, 陈巍1

摘要: 目的 比较达比加群酯与华法林对窦性心律左心功能不全扩张型心肌病患者抗凝治疗的有效性及安全性。方法 将符合入组标准的扩张型心肌病患者127例分为3组:对照组(42例,安慰药,po)、达比加群酯组(45例,150 mg,bid,po)及华法林组(40例,2.5 mg·d-1,po),规律门诊随访21个月。结果 对照组、达比加群酯组和华法林组血栓栓塞事件发生率分别为21.4%,0.0%,5.4%(P<0.01);出血事件发生率分别为2.3%,2.9%,18.9%(P<0.01)。达比加群酯组血栓栓塞事件发生率与华法林组差异无统计学意义(P>0.05),总出血事件发生率低于华法林组(P<0.05)。结论 抗凝治疗可有效降低窦性心律左心功能不全扩张型心肌病患者血栓栓塞事件发生率,且达比加群酯的不良反应事件发生率低于华法林。
关键词: 达比加群酯 ; 华法林 ; 心肌病 ; 扩张型 ; 抗凝治疗

Abstract:
Objective To compare the effectiveness and safety of the anticoagulant therapy between dabigatran etexilate and warfarin for patients with sinus arrhythmia in dilated cardiomyopathy Methods Total 127 patients with dilated cardiomyopathy who met the criteria of this research were divided into three groups, including the control group (42 patients, placebo, po), dabigatran etexilate group (45 patients, 150 mg,bid,po) and warfarin group (40 patients, 2.5 mg·d-1,po). Regular clinical follow-up lasted for 21 months. Results The incidence of thromboembolic events in the control group, dabigatran etexilate group and the warfarin group was 21.4%, 0.0%, 5.4% (P<0.01), and the incidence of bleeding events was 2.3%, 2.9% and 18.9% (P<0.01). There was no statistical difference of the incidence of thromboembolism between dabigatran etexilate group and warfarin group (P>0.05), and the incidence of total bleeding in dabigatran etexilate group was lower than that in warfarin group(P<0.05) Conclusion Anticoagulant therapy can effectively reduce the incidence of thromboembolic patients suffering from dilated cardiomyopathy with sinus rhythm and left ventricular dysfunction. Furthermore, as to the incidence rate of adverse events, dabigatran etexilate is lower than warfarin.
Key words: Dabigatran etexilate ; Warfarin ; Cardiomyopathy ; dilated ; Anticoagulation therapy

扩张型心肌病( dilated cardiomyopathy,DCM)是一类既有遗传因素又有非遗传因素所导致的复合型心肌疾病,其特征为进行性的心室扩大和收缩功能障碍。DCM是最常见类型的心肌病,发病率为1/2 500[1],为非缺血因素所致的充血性心力衰竭及心源性猝死的主要原因[2]

研究显示,伴有左心室射血分数<35%的窦性心律的DCM患者的栓塞事件率为4%[3]。但对该群体是否应予长期抗凝治疗却存在争议[4]。2013年10月—2015年5月,笔者观察了华法林及达比加群酯在窦性心律左心功能不全DCM患者抗凝治疗中的有效性及安全性,报道如下。

1 资料与方法
1.1 临床资料

入选我院住院部及门诊部确诊的DCM患者127例。诊断标准:排除继发性心肌损伤基础上的超声心动图提示①左心室射血分数<45%和(或)左心室短轴缩短速率<25%;②左心室舒张期末内径>2.7 cm·(m2)-1,体表面积(m2)=0.006 1×身高(cm)+0.012 8×体质量(kg)-0.152 9[5,6]。入选标准①年龄<75周岁;②合并高血压、糖尿病等高危因素,需行冠状动脉造影或冠脉血管成像检查前提下排除缺血性心肌病可能;③24 h动态心电图排除合并心律失常患者;④超声心动图提示左心室或双心室扩张,射血分数<35%的DCM患者,无相关心脏瓣膜损伤证据。排除标准:①预期生存期<2年的患者。②过敏体质或有药物禁忌史。③6个月内有颅内出血、消化道溃疡、生殖道出血者。④肝功能丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)高于正常值上限3倍者。⑤内生肌酐清除率(creatinine clearance rate,Ccr)<50 mL·min-1者。⑥可疑及确诊的出血性疾病、血小板减少症等。研究方案经我院伦理委员会批准,以上入选患者均签署知情同意书。结合患者个人意愿、经济及全身综合情况选择抗凝药物,对相关事项匹配(确保3组在性别、年龄、吸烟饮酒、合并危险因素等方面差异无统计学意义,若有则重新调整入组例数,必要时增减各组入组例数),最终入选对照组(42例)、达比加群酯组(45例)、华法林组(40)例。3组在性别、年龄、合并危险因素及吸烟饮酒等方面均差异无统计学意义(P>0.05)。

1.2 治疗方法

对照组给予安慰药(每片100 mg,含柠檬酸35 mg,华神药业有限公司)200 mg·d-1,不进行国际标准化比值(INR)监测,每个月常规随访1次至试验结束;达比加群酯组服用达比加群酯(德国勃林格殷格翰公司,批准文号:国药准字 J20130064)150 mg,bid,不进行INR监测,每个月常规随访1次至试验结束;华法林组初始剂量为华法林钠片(齐鲁制药有限公司,批准文号:国药准字H37021314,规格:每片2.5 mg)2.5 mg·d-1,连续用药5~7 d后根据INR调整剂量,随后每周测定INR1次,直至INR稳定波动在2.0~3.0,予维持剂量,调整监测INR时间为每个月1次,直至试验结束,各组均规律门诊随访21个月[7]。常规随访内容包括:系统心脏检查、24 h动态心电图、心脏彩超及相关实验室检查等。由心血管内科和神经内科医师共同对患者整体评估后决定是否行头颅CT、磁共振(MRI)或外周血管检查。

1.3 观察指标

血栓栓塞事件,包括缺血性脑卒中及非中枢神经系统栓塞事件:急性心肌梗死、全身各部位血栓栓塞、外周血管血栓形成等。②不良事件,包括严重出血(出血性脑卒中、消化道大出血、大咯血及其他大出血引起的重度贫血:一次出血量≥300 mL,血红蛋白下降>20 g·L-1);轻微出血(鼻出血、牙龈出血、皮肤瘀斑及瘀点、结膜下出血、肉眼血尿、咯血、血痰、黑便、阴道出血等)。

1.4 统计学方法

所有数据采用SPSS19.0版统计分析软件,计量资料以均数±标准差( x ¯ ±s)表示,若数据服从正态分布且方差齐,则多组间比较采用单因素方差分析及q检验,否则采用秩和检验。计数资料比较采用R×C列联表的χ2检验,若1/5以上的格子理论频数<5或有一个理论频数<1,则改用R×C表的Fisher确切概率法,以P<0.05为差异有统计学意义。多组间的两两比较则分割R×C列联表,对每个四格表行χ2检验或Fisher确切概率法。以P<0.016 7为差异有统计学意义。

2 结果
2.1 一般情况

21个月规律随访途中,华法林组有3例因不愿频繁抽血而停药退出,达比加群酯组有11例因经济原因而停药退出,总计14例退出。最终113例进入分析,对照组42例,达比加群酯组34例,华法林组37例,见表1。华法林达标维持剂量为(3.25±0.70) mg。

2.2 血栓栓塞事件

随访期间,113例患者共发生血栓栓塞事件11例(9.7%),其中对照组9例,达比加群酯组0例,华法林组2例,3组间总血栓栓塞事件发生率差异有统计学意义(P<0.01),但达比加群酯组总血栓栓塞事件发生率与华法林组差异无统计学意义(P=0.268),见表2。

3组患者一般资料比较

Comparison of baseline data among three groups of patients x¯±s

组别 例数 年龄/
身高/
cm
体质量/
kg
高血压病 糖尿病 吸烟史 饮酒史 ALT AST Ccr/
(μmol·L-1)
(U·L-1)
对照组 42 19 23 61.95±9.14 161.66±10.83 65.07±15.23 13 5 19 26 23.50±12.21 23.23±12.39 76.85±14.64
达比加群酯组 34 16 18 62.59±8.72 165.11±10.79 62.23±12.44 8 2 15 17 26.64±13.02 29.23±15.04 86.55±14.15
华法林组 37 20 17 60.41±9.12 160.89±11.22 66.83±8.48 10 3 17 20 23.43±11.73 23.54±11.72 83.10±14.35

3组血栓栓塞事件发生情况及血栓栓塞事件发生率比较

Comparison of thromboembolic events and its incidence among three groups of patients 例

组别 例数 短暂性脑
缺血发作
腔隙性
脑梗死
合并症状的
缺血性脑卒中
卒中 体循环
栓塞
外周血管
血栓形成
总血栓栓塞事
件发生率/%
对照组 42 3 2 3 0 1 0 21.4
达比加群酯组 34 0 0 0 0 0 0 0.0*1
华法林组 37 1 1 0 0 0 0 5.4*1

Compared with control group,*1P<0.01

与对照组比较,*1P<0.01

2.3 不良反应

见表3。随访期间,对照组共发生轻微出血事件1例,无严重出血事件;达比加群酯组共发生严重出血事件1例;华法林组共发生出血事件9例,其中严重出血事件3例。3组间总出血事件发生率差异有统计学意义(P<0.01),且达比加群酯组总出血事件发生率低于华法林组(P<0.05),但3组间严重出血事件发生率差异无统计学意义(P>0.05)。

3组患者出血事件发生情况比较

Comparison of bleeding events and its incidence among three groups of patients 例

组别 例数 出血性
脑卒中
消化道
大出血
牙龈
出血
皮肤
瘀斑
黑便 血尿 总不良事件
发生率/%
对照组 42 0 0 1 0 0 0 2.4*1
达比加群酯组 34 0 1 0 0 0 0 2.9*1*2
华法林组 37 2 1 2 2 1 1 24.3

Compared with warfarin group,*1P<0.01, *2P<0.05

与华法林组比较,*1P<0.01,*2P<0.05

3 讨论

达比加群酯是新型口服抗凝药,在抗凝治疗过程中,无需常规监测凝血指标,亦无需根据INR进行剂量或服药间隔的调整[8,9,10,11]。达比加群酯抗凝治疗时心房颤动、栓塞事件发生率较华法林更低,且出血率与华法林比较差异无统计学意义 [12,13],系统性栓塞事件相对风险降低58%,全因死亡率降低11%[3]

SAVE试验发现,左心室射血分数每下降5%,心肌梗死患者卒中风险增加18%[14];另一项大规模临床试验证实,在630例心力衰竭患者中,心力衰竭后脑卒中患者死亡率较无卒中患者增加2.3倍[15]。BAKALLI等[16]研究指出,在窦性心律合并左心室射血分数<35%的DCM患者中,13%患者终将合并左心室血栓,而68%患者终会出现左心耳血栓。以上研究均为在正常窦性心律左心室功能不全的DCM患者中使用口服抗凝药提供了理论基础。KOBER等[17]研究结果证实,在以上患者中使用华法林可将栓塞事件率由4%降至1.2%,本研究结果与之类似,达比加群酯及华法林均可使此类患者的总血栓栓塞事件发生率降低,但达比加群酯组总血栓栓塞事件发生率与华法林组差异无统计学意义(P>0.05)。提示对于正常窦性心律的左心室功能不全DCM患者仍需进行抗凝治疗,且达比加群酯在降低患者系统性栓塞事件相对风险方面不亚于华法林。

一项抗凝治疗前瞻性随机试验纳入左心室射血分数 <35%的特发性DCM患者197例,随机接受华法林或安慰药,结果显示安慰药组主要血栓栓塞终点事件发生率为10%,华法林组为6%[18]。在WASH试验[19]中,279例低射血分数患者被随机分配到华法林、阿司匹林或安慰药组,结果显示华法林比阿司匹林在降低卒中率方面略有优势,但以增加出血率为代价。以上几项国际大型前瞻性随机试验虽或因样本量不足或因随访时间不足使结果可信度下降,但仍有一定指导意义,且本研究结果与此类似,提示无论新型抗凝药达比加群酯还是传统抗凝药华法林,虽用药过程中出血风险增加,但多为一般出血风险,整体用药评价安全;达比加群酯在正常窦性心律左心室功能不全的DCM患者血栓事件的预防方面安全性优于华法林。

本研究为患者自愿服药基础上进行的前瞻性研究,依从性及可靠度较好,入选样本虽非随机对照研究,但设计者对其均进行了相关事项匹配,结果可信度较高。但本研究仍存在样本较小、观察指标不够全面的局限性。

NIEMEIJER等[20]报道,心力衰竭诊断后第1个月,患者发生缺血性卒中的风险较前大大增加,但在6个月内降至与前无异。另一项研究中,初次诊断为心力衰竭的患者在30 d内发生缺血性脑卒中的风险较前增加17.4倍[3]。故未来期待在大样本量、多中心研究的随机临床试验中进一步细化入选患者的心力衰竭阶段,力争使不同阶段的心力衰竭患者在抗凝治疗中获益最大化,最终达到减少特殊患者群体(窦性心律左心功能不全的DCM患者)的栓塞事件目的,以期为DCM患者提供更为全面的一级预防措施。

The authors have declared that no competing interests exist.

参考文献

[1] XIE X,LI C,ZHOU B,et al.Associations between TIM1 polymorphisms and dilated cardiomyopathy in a Han Chinese population[J].Int Heart J,2016,57(6):742-746.
DOI:10.1536/ihj.16-119      URL    
[本文引用:1]
[2] LAKDAWALA N K,WINTERFIELD J R,FUNKE B H.Dilated cardiomyopathy[J].Circ Arrhythm Electrophysiol,2013,13(6):228-237.
[本文引用:1]
[3] MISCHIE A N,CHIONCEL V,DROC I,et al.Anticoagula-tion in patients with dilated cardiomyopathy,lowejection fraction,and sinus rhythm:back to the drawing board[J].Cardiovasc Ther,2013,31(5):298-302.
Heart failure patients present an important thrombo-embolic risk, including symptomatic or silent peripheral arterial embolism, pulmonary embolism, and stroke. Patients in sinus rhythm who have concomitant depressed (< 35%) left ventricular ejection fraction have a 4% rate of embolic events. Several prospective randomized trials of anticoagulation in this group of patients were either underpowered or had a short period of follow-up. Even though in two studies warfarin had a slight advantage over aspirin (in the WATCH and WARCEF trials), it was at the cost of an increased risk in major hemorrhage. To decrease bleeding rates and to improve anticoagulant effect, new treatment strategies have to be tested. Novel anticoagulants (dabigatran, rivaroxaban, and apixaban) seem to be a promising alternative.
DOI:10.1111/1755-5922.12019      PMID:23279759      URL    
[本文引用:3]
[4] 张健. 扩张型心肌病[J].中国实用内科杂志,2012,7(32):484-487.
[本文引用:1]
[5] 陈灏珠. 实用心脏病学[M].5版.上海:上海科学技术出版社,2016:1059.
[本文引用:1]
[6] HEINZMANN D,GAWAZ M,SEIZER P,et al.Risk strati-fication in dilated cardiomyopathy:is the arrhythmogenic substrate stable over time?[J].JACC Heart Fail,2017,5(5):394.
[本文引用:1]
[7] YAO X X,ABRAHAM A S,SANGARALINGHAM L R,et al.Effectiveness and safety of dabigatran,rivaroxaban,and apixaban versus warfarin in nonvalvular atrial fibrillation[J].J Am Heart Associ,2016,5(6):e003725.
Background The introduction of non???vitamin K antagonist oral anticoagulants has been a major advance for stroke prevention in atrial fibrillation; however, outcomes achieved in clinical trials may not translate to routine practice. We aimed to evaluate the effectiveness and safety of dabigatran, rivaroxaban, and apixaban by comparing each agent with warfarin. Methods and Results Using a large US insurance database, we identified privately insured and Medicare Advantage patients with nonvalvular atrial fibrillation who were users of apixaban, dabigatran, rivaroxaban, or warfarin between October 1, 2010, and June 30, 2015. We created 3 matched cohorts using 1:1 propensity score matching: apixaban versus warfarin (n=15??390), dabigatran versus warfarin (n=28??614), and rivaroxaban versus warfarin (n=32??350). Using Cox proportional hazards regression, we found that for stroke or systemic embolism, apixaban was associated with lower risk (hazard ratio [HR] 0.67, 95% CI 0.46???0.98, P=0.04), but dabigatran and rivaroxaban were associated with a similar risk (dabigatran: HR 0.98, 95% CI 0.76???1.26, P=0.98; rivaroxaban: HR 0.93, 95% CI 0.72???1.19, P=0.56). For major bleeding, apixaban and dabigatran were associated with lower risk (apixaban: HR 0.45, 95% CI 0.34???0.59, P<0.001; dabigatran: HR 0.79, 95% CI 0.67???0.94, P<0.01), and rivaroxaban was associated with a similar risk (HR 1.04, 95% CI 0.90???1.20], P=0.60). All non???vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial bleeding. Conclusions In patients with nonvalvular atrial fibrillation, apixaban was associated with lower risks of both stroke and major bleeding, dabigatran was associated with similar risk of stroke but lower risk of major bleeding, and rivaroxaban was associated with similar risks of both stroke and major bleeding in comparison to warfarin.
DOI:10.1161/JAHA.116.003725      PMID:27412905      URL    
[本文引用:1]
[8] HUANG C,SIU M,VU L,et al.Factors influencing doctors'selection of dabigatran in non-valvular atrial fibrillation[J].J Eval Clin Pract,2013,19(5):938-943.
This study was designed to examine the factors that influence doctors' decision in initiating or switching from warfarin to dabigratran.A survey questionnaire was sent to 181 doctors who were most likely to prescribe dabigatran (e.g. cardiologists and general internists) at the University of California, San Francisco Medical Center between November 2011 and February 2012. Survey participants were asked to complete an electronic or a paper version of the questionnaire, which consisted of 17 multiple-choice questions. Fisher's exact test and Cochran-Mantel-Haenszel test were used to compare survey responses between cardiologists and general internists.A total of 65 survey responses were received (35.9% response rate). There were 13 cardiologists and 51 general internists who participated in the study. Cost (25%), renal function (21%) and CHADS2 score (18%) were the three factors doctors considered most often to determine a patient's eligibility for dabigatran in warfarin-na茂ve patients. On the other hand, histories of unstable international normalized ratio (37%) and missed appointments (17%) along with cost (19%) were most often considered in patients on warfarin. Cardiologists had prescribed dabigatran more often and had a significantly higher level of comfort with prescribing the drug than general internists (P = 0.003; 77% vs. 27%).Cost was the most important factor influencing doctors' decision to prescribe dabigatran. Safety and effectiveness of dabigatran as well as patient preference were additional factors influencing their decision. General internists were less comfortable with prescribing dabigatran than cardiologists.
DOI:10.1111/j.1365-2753.2012.01886.x      PMID:22834964      URL    
[本文引用:1]
[9] 孙迪迪,杨玉玲,袁冬冬. 达比加群和华法林治疗静脉血栓的临床对照观察[J].中国医院药学杂志 ,2017,37(5): 466-468.
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[10] 黄年旭,李园,陈锦华,王鹏.1例华法林过敏换用达比加群酯抗凝治疗患者的药学监护[J].医药导报,2015, 34(9): 1172-1173.
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[11] 张怡,龙萍,吕冬莲.1例心房颤动伴短暂性脑缺血抗凝治疗的药学监护[J].医药导报,2016, 35(8): 896-899.
目的 通过1例短暂性脑缺血伴心房颤动(房颤)患者抗凝治疗的药学监护,探讨对该类患者抗凝治疗思维及用药监护要点。方法 1例老年女性患者因房颤致短暂性脑缺血入院,初始给予华法林抗凝治疗,期间华法林国际标准化比值波动明显,分析华法林敏感原因,更换抗凝策略为口服达比加群酯至出院。临床药师协助制订个体化抗凝方案并提供相关治疗建议及用药教育。结果 抗凝治疗过程中,根据患者情况制订个体化给药方案并随时调整,患者1个月后好转出院。结论 临床药师开展抗凝治疗药学监护有助于患者个体化安全用药,同时积累了新型口服抗凝药的临床使用经验。
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[12] CONNOLLY S J,EZEKOWITZ M D,YUSUF S,et al.Dabigatran versus warfarin in patients with atrial fibrillation[J].N Engl J Med,2009,361(6):1139-1151.
Background: Edoxaban is a direct oral factor Xa inhibitor with proven antithrombotic effects. The long-term efficacy and safety of edoxaban as compared with warfarin in patients with atrial fibrillation is not known. Methods: We conducted a randomized, double-blind, double-dummy trial comparing two once-daily regimens of edoxaban with warfarin in 21,105 patients with moderate-to-high-risk atrial fibrillation (median follow-up, 2.8 years). The primary efficacy end point was stroke or systemic embolism. Each edoxaban regimen was tested for noninferiority to warfarin during the treatment period. The principal safety end point was major bleeding. Results: The annualized rate of the primary end point during treatment was 1.50% with warfarin (median time in the therapeutic range, 68.4%), as compared with 1.18% with high-dose edoxaban (hazard ratio, 0.79; 97.5% confidence interval [CI], 0.63 to 0.99; P<0.001 for noninferiority) and 1.61% with low-dose edoxaban (hazard ratio, 1.07; 97.5% CI, 0.87 to 1.31; P=0.005 for noninferiority). In the intention-to-treat analysis, there was a trend favoring high-dose edoxaban versus warfarin (hazard ratio, 0.87; 97.5% CI, 0.73 to 1.04; P=0.08) and an unfavorable trend with low-dose edoxaban versus warfarin (hazard ratio, 1.13; 97.5% CI, 0.96 to 1.34; P=0.10). The annualized rate of major bleeding was 3.43% with warfarin versus 2.75% with high-dose edoxaban (hazard ratio, 0.80; 95% CI, 0.71 to 0.91; P<0.001) and 1.61% with low-dose edoxaban (hazard ratio, 0.47; 95% CI, 0.41 to 0.55; P<0.001). The corresponding annualized rates of death from cardiovascular causes were 3.17% versus 2.74% (hazard ratio, 0.86; 95% CI, 0.77 to 0.97; P=0.01), and 2.71% (hazard ratio, 0.85; 95% CI, 0.76 to 0.96; P=0.008), and the corresponding rates of the key secondary end point (a composite of stroke, systemic embolism, or death from cardiovascular causes) were 4.43% versus 3.85% (hazard ratio, 0.87; 95% CI, 0.78 to 0.96; P=0.005), and 4.23% (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.32). Conclusions: Both once-daily regimens of edoxaban were noninferior to warfarin with respect to the prevention of stroke or systemic embolism and were associated with significantly lower rates of bleeding and death from cardiovascular causes. (Funded by Daiichi Sankyo Pharma Development; ENGAGE AF-TIMI 48 ClinicalTrials.gov number, NCT00781391.)
DOI:10.1056/NEJMoa0905561      PMID:20042760      URL    
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[13] 吴玥,冯静,彭燕,. 新型抗凝药与华法林用于非瓣膜性房颤患者卒中防治的成本效果分析[J].中国医院药学杂志,2016,36(12):1003-1007.
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[14] LOH E,SUTTON M S,WUN C C,et al.Ventricular dysfu-nction and the risk of stroke after myocardial infarction[J].N Engl J Med,1997,336(4):251-257.
DOI:10.1056/NEJM199701233360403      URL    
[本文引用:1]
[15] FREUDENBERGER R S,HELLKAMP A S,HALPERIN J L,et al.Risk of thromboembolism in heart failure:an analysis from the sudden cardiac death in heart failure trial (SCD-HeFT)[J].Circulation,2007,115(20):2637-2641.
BACKGROUND -In patients with heart failure,rates of clinically apparent stroke range from 1.3% to 3.5% per year. Little is known about the incidence and risk factors in the absence of atrial fibrillation. In the Sudden Cardiac Death in Heart Failure Trial(SCD-HeFT),2521 patients with moderate heart failure were randomized to receive amiodarone,implanted cardioverter-defibrillators(ICDs),or placebo. METHODS AND RESULTS -We determined the incidence of stroke or peripheral or pulmonary embolism in patients with no history of atrial fibrillation(n=2114),predictors of thromboembolism and the relationship to left ventricular ejection fraction. Median follow-up was 45.5 months. Kaplan-Meier estimates(95% CIs) for the incidence of thromboembolism by 4 years were 4.0% (3.0% to 4.9% ),with 2.6% (1.1% to 4.1% ) in patients randomized to amiodarone,3.2% (1.8% to 4.7% ) in patients randomized to ICD,and 6.0% (4.0% to 8.0% ) in patients randomized to placebo(approximate rates of 0.7% ,0.8% ,and 1.5% per year,respectively). By multivariable analysis,hypertension(P=0.021) and decreasing left ventricular ejection fraction(P=0.023) were significant predictors of thromboembolism; treatment with amiodarone or ICD treatment was a significant predictor of thromboembolism-free survival(P=0.014 for treatment effect; hazard ratio95% CI versus placebo,0.570.33 to 0.99 for ICD; 0.440.24 to 0.80 for amiodarone). Inclusion of atrial fibrillation during follow-up in the multivariable model did not affect the significance of treatment assignment as a predictor of thromboembolism. CONCLUSIONS -In the SCD-HeFT patient cohort,which reflects contemporary treatment of patients with moderately symptomatic systolic heart failure,patients experienced thromboembolism events at a rate of 1.7% per year without antiarrhythmic therapy. Those treated with amiodarone or ICDs had lower risk of thromboembolism than those given placebo. Hypertension at baseline and lower ejection fraction were independent predictors of risk.
DOI:10.1111/j.1527-5299.2007.06240-2.x      PMID:17485579      URL    
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[16] BAKALLI A,GEORGIEVSKA-ISMAIL L,KOçINAJ D,et al.Prevalence of left chamber cardiac thrombi in patients with dilated left ventricle at sinus rhythm:the role of transesophageal echocardiography[J].J Clin Ultrasound,2013,41(1):38-45.
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[17] KOBER L,TORP-PEDERSEN C,MCMURRAY J J,et al.Increased mortality after dronedarone therapy for severe heart failure[J].N Engl J Med,2008,358(25):2678-2687.
Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone, but it does not contain iodine and thus does not cause iodine-related adverse reactions. Therefore, it may be of value in the treatment of patients with heart failure.In a multicenter study with a double-blind design, we planned to randomly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of dronedarone twice a day or placebo. The primary end point was the composite of death from any cause or hospitalization for heart failure.After inclusion of 627 patients (310 in the dronedarone group and 317 in the placebo group), the trial was prematurely terminated for safety reasons, at the recommendation of the data and safety monitoring board, in accordance with the board's predefined rules for termination of the study. During a median follow-up of 2 months, 25 patients in the dronedarone group (8.1%) and 12 patients in the placebo group (3.8%) died (hazard ratio in the dronedarone group, 2.13; 95% confidence interval [CI], 1.07 to 4.25; P=0.03). The excess mortality was predominantly related to worsening of heart failure--10 deaths in the dronedarone group and 2 in the placebo group. The primary end point did not differ significantly between the two groups; there were 53 events in the dronedarone group (17.1%) and 40 events in the placebo group (12.6%) (hazard ratio, 1.38; 95% CI, 0.92 to 2.09; P=0.12). More increases in the creatinine concentration were reported as serious adverse events in the dronedarone group than in the placebo group.In patients with severe heart failure and left ventricular systolic dysfunction, treatment with dronedarone was associated with increased early mortality related to the worsening of heart failure. (ClinicalTrials.gov number, NCT00543699.)
DOI:10.1056/NEJMoa0800456      PMID:18565860      URL    
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[18] COKKINOS D V,HARALABOPOULOS G C,KOSTIS J B,et al.Efficacy of antithrombotic therapy in chronic heart failure:the HELAS study[J].Eur J Heart Fail,2006,8(4):428-432.
Abstract Top of page Abstract 1.Introduction 2.Methods 3.Results 4.Discussion Appendix A. HELAS Committees and Investigators References Background: It is not clear if long-term antithrombotic treatment has a beneficial effect on the incidence of thromboembolism in chronic heart failure (CHF). The HELAS study (Heart failure Long-term Antithrombotic Study) is a multicentre, randomised, double-blind, placebo-controlled trial to evaluate antithrombotic treatment in patients with CHF. Methods: 197 HF patients (EF <35%) were enrolled. Patients with Ischaemic Heart Disease were randomised to receive either aspirin 325 mg or warfarin. Patients with Dilated Cardiomyopathy (DCM) were randomised to receive either warfarin or placebo. Results: Analysis of the data from 312 patient years showed an incidence of 2.2 embolic events per 100 patient years, with no significant difference between groups. The incidence of myocardial infarction, hospitalisation, exacerbation of heart failure, death and haemorrhage were not different between the groups. No peripheral or pulmonary emboli were reported. Echocardiographic follow-up for 2 years showed an overall increase in left ventricular ejection fraction from 28.2卤6 to 30.3-7 p <0.05, which was most obvious in patients with DCM taking warfarin (EF 26.8卤5.3 at baseline, 30.7卤10 at 2 years, p <0.05). Conclusions: (1) Overall embolic events are rare in heart failure regardless of treatment. (2) Treatment does not seem to affect outcome.
DOI:10.1016/j.ejheart.2006.02.012      PMID:16737850      URL    
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[19] CLELAND J G F,FINDLAY I,JAFRI S,et al.The warfarin/aspirin study in heart failure (WASH):a randomized trial comparing antithrombotic strategies for patients with heart failure[J].Am Heart J,2004,148(1):157-164.
The Warfarin/Aspirin Study in Heart failure (WASH) provides no evidence that aspirin is effective or safe in patients with heart failure. The benefits of warfarin for patients with heart failure in sinus rhythm have not been established. Antithrombotic therapy in patients with heart failure is not evidence based but commonly contributes to polypharmacy.
DOI:10.1016/j.ahj.2004.03.010      PMID:15215806      URL    
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[20] NIEMEIJER M N,LEENING M J,VAN DEN BERG M E,et al.Subclinical abnormalities in echocardiographic parameters and risk of sudden cardiac death in a general population:the rotterdam study[J].J Card Fail,2016,22(1):17-23.
Abstract BACKGROUND: Subclinical cardiac dysfunction has been associated with increased mortality, and heart failure increases the risk of sudden cardiac death (SCD). Less well known is whether subclinical cardiac dysfunction is also a risk factor for SCD. Our objective was to assess the association between echocardiographic parameters and SCD in a community-dwelling population free of heart failure. METHODS AND RESULTS: We computed hazard ratios (HRs) for left atrium diameter, left ventricular (LV) end-diastolic dimension, LV end-systolic dimension, LV mass, qualitative LV systolic function, LV fractional shortening, and diastolic function. During a median follow-up of 6.3 years in 4,686 participants, 68 participants died because of SCD. Significant associations with SCD were observed for qualitative LV systolic function and LV fractional shortening. For moderate/poor qualitative LV systolic function, the HR for SCD was 2.54 (95% confidence interval [CI] 1.10-5.87). Each standard deviation decrease in LV fractional shortening was associated with an HR of 1.36 (95% CI 1.09-1.70). CONCLUSIONS: Subclinical abnormalities in LV systolic function were associated with SCD risk in this general population. Although prediction of SCD remains difficult and traditional cardiovascular risk factors are of greatest importance, this knowledge might guide future directions to prevent SCD in persons with subclinical cardiac dysfunction. Copyright 2016 Elsevier Inc. All rights reserved.
DOI:10.1016/j.cardfail.2015.06.007      PMID:26093333      URL    
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关键词(key words)
达比加群酯
华法林
心肌病
扩张型
抗凝治疗

Dabigatran etexilate
Warfarin
Cardiomyopathy
dilated
Anticoagulation therapy

作者
武丽萍
胡立禄
杜鹃
贾国渠
陈巍

WI Liping
HU Lilu
DU Juan
JIA Guoqu
CHEN Wei