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1、心房颤动抗栓治疗进展The Epidemiology of AF in China and other Countries5.5%5.4%50 yrs,USA(CHS),single ECG 65 yrs,UK,single ECG 60 yrs,Netherlands,single ECG&medical record 50 yrs,UK,single ECG 55 yrs,Netherlands,single ECG 35 yrs,USA,medical record 50 yrs,UK,single ECG Review results 60 yrs,Australia,triennia
2、l survey 40 yrs,Japan,single ECG 60 yrs,Hong Kong,single ECG 35 yrs,main land,China,single ECG 35 yrs,Denmark,single ECG25-64 yrs,west German,single ECG 15 yrs,India,single ECG 0.1%5.1%3.7%3.0%2.8%2.4%1.5%1.3%1.3%0.77%0.60%0.28%Patients with AF In China 8 millionThe Epidemic of Atrial FibrillationIn
3、creasing prevalence of risk factors for AF:n Older agen Systemic hypertensionn Heart failuren Valvular heart diseasen Diabetes mellitusn ObesityPrevalence of Stroke in Patients with NV AF Stratified by Age years0510152025Prevalence(%)3040 40 49 6069 50-59 7079 80HU D,et al.Chin J Intern Med,2003;42:
4、157-161Combined Endpoint Combined Endpoint Occurrence(%)Occurrence(%)Follow-up（m）0 6 12 18 2402015105Aspirin(150-160mg)Warfarin(INR2.0-3.0)RRR 36%13.0%8.4%Net Clinical OutcomeThe Randomized Prospective Trial compared aspirin with adjusted dose warfarin in NVAF Patients P=0.01The Covalent Group,Inc.T
5、he optimal intensity of anticoagulation4.0INREmbolic Hemorrhage 43.53.02.52.01.51.00.50INR 2-3The Absolute Incidence of Bleeding Balancing Risk and Benefitn Improve risk stratificationn Improve anticoagulation controln Minimize use of concomitant antiplatelet therapyn New antithrombotic therapiesBal
6、ancing Risk and Benefitn Improve risk stratificationRelative Distribution of Patients by applying differentrisk stratification schemesThe stratification schemes were applied to a stratified random sample of 1000 patients was selected from Stroke Prevention in Atrial Fibrillation III participants22,2
7、3Balancing Risk and Benefitn Improve risk stratificationn Improve anticoagulation controlVariable Dose Responsen Drug interference Most potent:Amiodarone(inhibits R-and S-enantiomers)Most under-appreciated:Paracetamol(touted interference with enzymes of the vitamin K cycle)n Dietary vitamin KThis pa
8、thway illustrates genes thought to mediate the eVects of warfarin.It also depicts a simpli-Wed representation of the biotransformation of warfarin and vitamin KAssociation of warfarin dose with genes involved in its action and metabolismVKORC1 Related to Dose of WarfarinJ.Med.Genet.published online
9、12 Apr 2006;Patients with homozygous of the dose of warfarin doubled（27mg/w 47mg/w）Pie chart showing the known sources of variability in warfarin dose needed for a stable INR.Each estimate is based on a summary analysis of partial r2 values from multivariate regression analysis reported in six studi
10、es that included genotyping on both CYP2C9 and VKORC1Factors Contribute to Stable Dose WarfarinOBJECTIONS TO GENETIC TESTING:Warfarinn 1.Considered costly,inconvenient.(Coverage by CMS just shifts costs.)n 2.Slows down prescribing warfarin.n 3.Not proven to be as good or superior to the current stan
11、dard of care(“educated guess”approach)which is getting better.n 4.Will genetic profiling improve maintenance dosing?If so,how?n 5.Can Anticoag Clinics/POC testing improve warfarin anticoagulation more than rapid turnaround genetic testing?n 6.Novel anticoagulantsfixed dose,no coagulation monitoringM
12、odels of AC Management Routine medical care or usual care(UC)1 Anticoagulation clinic care(ACC)1 Point-of-care(POC)testing2 Provider testing and dosing Patient self-testing(PST),but Dosing by provider Patient self-management(PSM),with Dosing by patientBalancing Risk and Benefitn Improve risk stratif
13、icationn Improve anticoagulation controln Minimize use of concomitant antiplatelet therapyRecommendation of patients with indications of long-term oral anticoagulation after PCIBalancing Risk and Benefitn Improve risk stratificationn Improve anticoagulation controln Minimize use of concomitant antip
14、latelet therapyn New antithrombotic therapies左心耳堵闭术取代药物抗凝？PLAATO WatchmanNew anticoagulants新型抗凝药物特性Rivaroxaban Apixaban Dabigatran Etexilate目标 a因子 a因子 凝血酶用药途径 口服 口服 口服前体药 无 无 无生物利用度(%)80 50 6峰浓度时间3 3 2半衰期9 9-14 14-17给药次数 每日一次 每日两次 每日一次或两次药物相互作用 CYP3A4和P-糖蛋白抑制剂CYP3A4和P-糖蛋白抑制剂质子泵抑制剂肾脏清除66 25 80妊娠的安全性
15、否 否 否拮抗药物 无 无 无Comparison of idraparinux with vitamin K antagonists forprevention of thromboembolism-Kaplan-Meierfirst confirmed symptomatic recurrent stroke or non-CNS systemic embolismFirst clinically relevant bleeding during the randomised treatment periodLancet 2008;371:31521stop after randomisa
16、tion of 4576 patients,mean follow-up period of 107 新型抗凝药物-利伐沙班低危因素 中危因素 高危因素年龄65-75岁女性甲亢冠心病 卒中、TIA动脉栓塞风湿性瓣膜病人工瓣膜置换年龄75岁高血压糖尿病心力衰竭LVEF35%或FS25%ACC/AHA心房颤动指南2006结 论 n心房颤动是卒中的重要危险因素。n中高危房颤患者，监测下调整剂量华法林（INR 2.0-3.0），中国人同样适用；但多数AF患者没有进行抗凝治疗。n房颤抗栓策略选择：血栓/出血的平衡。n新型抗凝药物可能是未来抗凝的方向，简便、无需监测。n长期抗凝治疗管理，建立抗凝门诊。抗凝
17、治疗的管理nn抗凝门诊 1nn患者手提式自我监测仪 2,3nn计算机辅助 4,51 Arch Intern Med 1998;158:1641-72 Thromb Haemost 2000;839:661-53 Lancet 2000;356:97-1024 Lancet 1998;352:1505-95 Thromb Haemost 2000;83:849-52严重出血的发生率13559名房颤病人颅内出血的发生率J Am Geriatr Soc 2006;54:1231-1236年龄服华法林事件数（n）率（95%CI）未服华法林事件数（n）率（95%CI）服华法林未服华法林 年事件发生率（%
18、）血栓栓塞和出血事件与INR4.0INR血栓栓塞 出血43.53.02.52.01.51.00.50接受华法林治疗的房颤病人发生严重出血的危险因素：HEMORR2HAGESAm Heart J 2006;151:713-719肝、肾疾病 1酒精滥用 1恶性肿瘤 1老年 1血小板计数减少 1再次出血危险 2高血压 1贫血 1遗传因素-额外的跌倒危险 1中风 1ACC/AHA心房颤动指南2006类推荐n 除孤立性房颤和有禁忌证外，所有房颤患者均建议服用抗栓药物以预防血栓栓塞。（A）n 抗栓药物的选择根据卒中和出血的绝对危险，对患者的相对危险和获益。（A）n 监测INR频率：初始用药时至少每周一次，
19、稳定后每月一次。（A）n 因手术需要中断抗凝治疗超过1周以上的高危患者，给与普通肝素或低分子肝素替代，尽管这些替代治疗的疗效还不确定。（b C）芬兰6家医院2003-2004调查European Heart Journal(2007)28,726732房颤患者进行PCI的抗栓治疗Gregory Y.H.Lip and Manas Karpha Chest 2006;130;1823-1827INR异常升高的处理建议INR 5 9 20减量或停用一次停用1-2次 VK1 1-2.5mg#VK1 2-5mg停用VK1 3-5mg 严重出血/严重过量 静脉VK1（10mg）新鲜血浆或浓缩凝血酶原VK1/12小时*出血危险因素：近期出血病史，酗酒，肝肾功能不全，应用阿司匹林或其他非甾体抗炎药#急诊手术或拔牙，快速逆转 治疗与研究方向