心房颤动抗栓治疗进展课件

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1、心房颤动抗栓治疗进展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 resul

2、ts 60 yrs, Australia, triennial 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 ECG0.1%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

3、million心房颤动抗栓治疗进展The Epidemic of Atrial FibrillationIncreasing prevalence of risk factors for AF:nOlder agenSystemic hypertensionnHeart failurenValvular heart diseasenDiabetes mellitusnObesity心房颤动抗栓治疗进展Prevalence of Stroke in Patients with NVAF Stratified by Age years0510152025Prevalence (%)30404049

4、606950-59707980HU D, et al. Chin J Intern Med, 2003; 42: 157-161心房颤动抗栓治疗进展Efficacy of Warfarin in Atrial Fibrillation心房颤动抗栓治疗进展Combined Endpoint Combined Endpoint Occurrence (%)Occurrence (%)Follow-up（m）0612182402015105Aspirin (150-160mg)Warfarin (INR2.0-3.0)RRR 36 %13.0%8.4%Net Clinical OutcomeThe

5、Randomized Prospective Trial compared aspirin with adjusted dose warfarin in NVAF Patients P=0.01心房颤动抗栓治疗进展The optimal intensity of anticoagulation4.0INREmbolic Hemorrhage 43.53.02.52.01.51.00.50INR 2-3心房颤动抗栓治疗进展心房颤动抗栓治疗进展Anticoagulation of AF in Real-life 10090807060504030201053.5%9.8%37.0%43.7%8.9

6、%47.3%No antithromboticWarfarinaspirinEligible* (n=3944) Ineligible (n=562)*patients with at least one high-moderate risk factors according to ACC/AHA guideline 2006心房颤动抗栓治疗进展心房颤动抗栓治疗进展The Absolute Incidence of Bleeding 心房颤动抗栓治疗进展Hemorrhage of in-hospital patients with NVAF in ChinaHu D, et al. 2004

7、 Chin J Intern Med P=0.001 WARFARIN ASPIRIN NO1.4%6.33.3%MINOR（5.3%）MAJOR（1%）%987654321心房颤动抗栓治疗进展心房颤动抗栓治疗进展The Dilemma of Anticoagulation ManagementnWarfarin has a narrow therapeutic window of effectiveness and safety.nMany factors influence a patients stability in that window.nFrequent monitoring i

8、s required to maintain patients in the therapeutic window.nMonitoring is labor intensive and complex.nPhysicians avoid warfarin use because of its complexity.心房颤动抗栓治疗进展Balancing Risk and BenefitnImprove risk stratificationnImprove anticoagulation controlnMinimize use of concomitant antiplatelet ther

9、apynNew antithrombotic therapies心房颤动抗栓治疗进展Balancing Risk and BenefitnImprove risk stratification心房颤动抗栓治疗进展心房颤动抗栓治疗进展Relative Distribution of Patients by applying differentrisk stratification schemesThe stratification schemes were applied to a stratified random sample of 1000 patients was selected fr

10、om Stroke Prevention in Atrial Fibrillation III participants22,23心房颤动抗栓治疗进展Balancing Risk and BenefitnImprove risk stratificationnImprove anticoagulation control心房颤动抗栓治疗进展Variable Dose ResponsenDrug interference Most potent:Amiodarone (inhibits R- and S-enantiomers)Most under-appreciated:Paracetamol

11、 (touted interference with enzymes of the vitamin K cycle)nDietary vitamin K心房颤动抗栓治疗进展This pathway 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 invol

12、ved in its action and metabolism心房颤动抗栓治疗进展VKORC1 Related to Dose of WarfarinJ. Med. Genet. published online 12 Apr 2006;Patients with homozygous of the dose of warfarin doubled（27mg/w 47mg/w）心房颤动抗栓治疗进展GENOTYPE VS STANDARD WARFARIN DOSING Couma-Gen Trial (N=206)nRapid turnaround CYP2C9 and VKORC1 tes

13、ting vs. “empiric”nPrimary endpoint: TTR nSmaller and fewer dosing changes with genetic testingnNo difference in TTRCirculation 2007; 116: 2563-2570心房颤动抗栓治疗进展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 p

14、artial r2 values from multivariate regression analysis reported in six studies that included genotyping on both CYP2C9 and VKORC1Factors Contribute to Stable Dose Warfarin心房颤动抗栓治疗进展OBJECTIONS TO GENETIC TESTING: Warfarinn1. Considered costly, inconvenient. (Coverage by CMS just shifts costs.)n2. Slo

15、ws down prescribing warfarin.n3. Not proven to be as good or superior to the current standard of care (“educated guess” approach)which is getting better.n4. Will genetic profiling improve maintenance dosing? If so, how?n5. Can Anticoag Clinics/ POC testing improve warfarin anticoagulation more than

16、rapid turnaround genetic testing?n6. Novel anticoagulantsfixed dose, no coagulation monitoring心房颤动抗栓治疗进展Models 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

17、by provider Patient self-management (PSM), with Dosing by patient心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展Balancing Risk and BenefitnImprove risk stratificationnImprove anticoagulation controlnMinimize use of concomitant antiplatelet therapy心房颤动抗栓治疗进展心房颤动抗栓治疗进展Recommendation of patients with indications of lon

18、g-term oral anticoagulation after PCI心房颤动抗栓治疗进展Balancing Risk and BenefitnImprove risk stratificationnImprove anticoagulation controlnMinimize use of concomitant antiplatelet therapynNew antithrombotic therapies心房颤动抗栓治疗进展左心耳堵闭术取代药物抗凝？左心耳堵闭术取代药物抗凝？PLAATO Watchman心房颤动抗栓治疗进展New anticoagulants心房颤动抗栓治疗进展

19、新型抗凝药物特性特性RivaroxabanRivaroxabanApixabanApixabanDabigatran Dabigatran EtexilateEtexilate目目标标aa因子因子aa因子因子凝血凝血酶酶用用药药途径途径口服口服口服口服口服口服前体前体药药无无无无无无生物利用度生物利用度(%)(%)808050506 6峰峰浓浓度度时间时间3 33 32 2半衰期半衰期9 99-149-1414-1714-17给药给药次数次数每日一次每日一次每日两次每日两次每日一次或两次每日一次或两次药药物相互作用物相互作用CYP3A4CYP3A4和和P-P-糖蛋白抑糖蛋白抑制制剂剂CYP3A

20、4CYP3A4和和P-P-糖蛋白糖蛋白抑制抑制剂剂质质子子泵泵抑制抑制剂剂肾脏肾脏清除清除666625258080妊娠的安全性妊娠的安全性否否否否否否拮抗拮抗药药物物无无无无无无心房颤动抗栓治疗进展Comparison of idraparinux with vitamin K antagonists forprevention of thromboembolism-Kaplan-Meierfirst confirmed symptomatic recurrent stroke or non-CNS systemic embolismFirst clinically relevant blee

21、ding during the randomised treatment periodLancet 2008; 371: 31521stop after randomisation of 4576 patients, mean follow-up period of 107 心房颤动抗栓治疗进展新型抗凝药物-利伐沙班心房颤动抗栓治疗进展心房颤动抗栓治疗进展低危因素 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心房颤动抗栓治疗进展结 论 n心房颤动是卒中的重

22、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。心房颤动抗栓治疗进展心房颤动抗栓治疗进展抗凝治疗的管理抗凝治疗的管理n n抗凝门诊 1n n患者手提式自我监测仪 2,3n n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;3

23、52:1505-95 Thromb Haemost 2000;83:849-52心房颤动抗栓治疗进展严重出血的发生率心房颤动抗栓治疗进展13559名房颤病人名房颤病人颅内出血的发生率颅内出血的发生率J Am Geriatr Soc 2006;54:1231-1236年龄年龄服华法林事件数（服华法林事件数（n）率（率（95%CI）未服华法林事件数（未服华法林事件数（n）率（率（95%CI）服华法林服华法林未服华法林未服华法林 年事件发生率（年事件发生率（%）心房颤动抗栓治疗进展血栓栓塞和出血事件与INR4.0INR血栓栓塞血栓栓塞 出血出血43.53.02.52.01.51.00.50心房颤动抗

24、栓治疗进展接受华法林治疗的房颤病人发生严重出接受华法林治疗的房颤病人发生严重出血的危险因素：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1心房颤动抗栓治疗进展ACC/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，稳定后每月一次。（A）n因手术需要中断抗凝治疗

25、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）心房颤动抗栓治疗进展芬兰6家医院2003-2004调查European Heart Journal (2007) 28, 726732心房颤动抗栓治疗进展心房颤动抗栓治疗进展房颤患者进行PCI的抗栓治疗Gregory Y. H. Lip and Manas Karpha Chest 2006;130;1823-1827心房颤动抗栓治疗进展INR异常升高的处理建议INR 5 9 20减量或减量或停用一次停用一次停用停用1-2次次 VK1 1-2.5mg #VK1 2-5mg停用停用VK1 3-5mg

26、严重出血严重出血/严重过量严重过量 静脉静脉VK1（10mg）新鲜血浆或浓缩新鲜血浆或浓缩凝血酶原凝血酶原VK1/12小时小时*出出血血危危险险因因素素：近近期期出出血血病病史史，酗酗酒酒，肝肝肾肾功功能能不不全全，应应用用阿阿司司匹匹林林或或其其他非甾体抗炎药他非甾体抗炎药#急诊手术或拔牙，快速逆转急诊手术或拔牙，快速逆转 心房颤动抗栓治疗进展治疗与研究方向心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展Moderate-risk factorsHigh-risk factorsage 75previous strokehypertensi

27、onmitral valve stenosisHeart failure prosthetic heart valve diabetes Preventing ThromboembolismRisk categoryrecommended therapyNo risk factorsASA 81-325mg QDOne moderate risk factorASA 81-325 QDor warfarinAny high-risk factorOr 1 moderate-risk factorWarfarin心房颤动抗栓治疗进展ACTIVE研究设计Documented AF + 1 risk

28、 factor:Age 75, Hypertension, Prior stroke/TIA, LVEF45, PAD, Age 55-74 + CAD or diabetesACTIVE WClopidogrel+ASA vs. OAC Contra-indications to OAC or UnwillingACTIVE AClopidogrel+ASA vs. ASANo Exclusion criteria for ACTIVE IACTIVE IIrbesartan vs placebo6500 patients7500 patients9000 patientsClopidogr

29、el 75mg +ASA 75-100 mg OAC (INR 2.0 3.0)心房颤动抗栓治疗进展ACTIVE W - 主要终点Stroke, Non-CNS Systemic Embolism, MI & Vascular DeathCumulative Hazard Rates 年年# at RiskC+A 3335 3149 2387 916OAC 3371 3220 2453 9113.93 %/year5.64 %/yearRR = 1.45P = 0.0002心房颤动抗栓治疗进展ACTIVE W结果- 严重出血Cumulative Hazard Rates # at RiskC+

30、A 3335 3172 2403 914OAC 3371 3212 2423 9012.4 %/year2.2 %/yearRR = 1.06P = 0.67心房颤动抗栓治疗进展ACTIVE W主要终点 OutcomeRate per 100 patient yearsC+A vs. OACOACC+ARR95% CIp主要终点主要终点3.935.641.451.19-1.770.0002 卒中卒中 1.402.441.751.27-2.410.0006 MI0.550.841.540.91-2.600.11 非中枢神经栓塞非中枢神经栓塞0.100.485.131.75-15.00.0028

31、血管死亡血管死亡2.572.851.110.85-1.440.45总死亡3.803.801.000.80-1.251.00心房颤动抗栓治疗进展n高危房颤患者，三氟醋柳酸联合华法林优于单独抗凝或抗血小板，尤其是极高危AF患者（血栓栓塞事件），出血无显著差异。n联合抗凝治疗中，为减少出血可适当降低抗凝治疗强度，但INR1.8-1.9无效。n三氟醋柳酸（triflusal）600mg相当于阿司匹林300mg，但出血明显减少。NASPEAF 研究结论心房颤动抗栓治疗进展新型抗凝药物新型抗凝药物TFPI (tifacogin)FondaparinuxIdraparinuxRivaroxabanLY517

32、717YM150DU-176bXimelagatranDabigatranORALPARENTERALDX-9065aXaIIaTF/VIIaXIXIXaVIIIaVaIIFibrinFibrinogenATAPC (drotrecogin alfa)sTM (ART-123)Adapted from Weitz & Bates. J Thromb Haemost 2005TTP889心房颤动抗栓治疗进展直接凝血酶抑制剂ximelagtran心房颤动抗栓治疗进展-AMADEUS研究 -idraparinux 心房颤动抗栓治疗进展达比加群RELY心房颤动抗栓治疗进展新型抗凝药物存在的问题新型抗凝

33、药物存在的问题nAmadeus研究是近期第3个替代华法林失败的研究。第一个研究是SPORTIF，该研究显示直接凝血酶抑制剂ximelagatran与华法林同样有效且出血并发症降低，但是其肝脏毒性大。ACTIVE-W研究显示华法林优于双重抗血小板治疗，同时证实即使强化的抗血小板治疗也不能有效预防心房的血栓栓塞。在Amadeus研究中idraparinux组出血发生率较高，提示正确药物的正确剂量十分重要。心房颤动抗栓治疗进展2% 华法林华法林60% 无抗凝无抗凝阿司匹林阿司匹林38%中国心房颤动抗栓治疗现状胡大一等。中华内科杂志，2004；孙艺红等。中华内科杂志，2004；43：258-260 9

34、.64%华法林华法林90.36% 非抗凝非抗凝人群流调人群流调 住院病人住院病人心房颤动抗栓治疗进展VKORC1基因多态性与华法林的初始剂量相关基因多态性与华法林的初始剂量相关J. Med. Genet. published online 12 Apr 2006;1542 G/G 、 2255C/C 及1173C/C纯合子患者的华法林周剂量倍增27mg to 47mg心房颤动抗栓治疗进展华法林的个体差异基因多态性http:/心房颤动抗栓治疗进展围手术期抗凝围手术期抗凝高危 肝素 15000U bid 低分子肝素100U/kg 术前24小时停用 静脉滴注（1300U/h）至术前5小时停用 术前

35、术后*术后12小时同时给予肝素与华法林持续45天直至INR达标*术后出血高危，肝素和低分子肝素推迟24小时或更长的时间。对牙科操作，可以用氨甲环酸、氨基乙酸漱口，不需要停用抗凝药物。 中危 术前45天停用华法林 使INR3 x ULNALT 3 x ULN6.56.50.70.7P0.001P0.001心房颤动抗栓治疗进展主要终点：卒中和栓塞(Intention-to-Treat)-3-3-2-2-1-100112233Treatment duration (moTreatment duration (mo)Cumulative event rate (%)Cumulative event r

36、ate (%)WarfarinWarfarinXimelagatranXimelagatran56 events =56 events =2.3%/yr2.3%/yr4040 events = events =1.6%/yr1.6%/yrXimelagatranXimelagatranBetterBetterWarfarinWarfarinBetterBetterEvent rate difference (%)Event rate difference (%)SuperioritySuperiorityNon-inferiorityRR 29%RR 29%AR 0.7%AR 0.7%心房颤动

37、抗栓治疗进展有效抗凝有效抗凝出血并发症出血并发症INR（2.0-3.0）积极治疗高血压和糖尿病积极治疗高血压和糖尿病心房颤动抗栓治疗进展心房颤动抗栓治疗进展Adverse EventsHemorrhage EventEventraterate(%/yr)(%/yr)WarfarinWarfarinXimelagatranXimelagatran0.20.20.50.51.81.81.31.329.529.525.525.5P=NSP=NSP=NSP=NSP=0.007P=0.007心房颤动抗栓治疗进展Combined Major Adverse EventsOn-Treatment Analy

38、sisEventEventraterate(%/yr)(%/yr)4.64.66.16.1RRR = 25%RRR = 25%P=0.022P=0.022Primary events + major bleeding + deathPrimary events + major bleeding + death心房颤动抗栓治疗进展紧急复律心房颤动复律择期复律UFH IV（C） 持续75 岁高血压糖尿病LA血栓收缩压1.76 (1.08-2.89)1.52 (1.28-1.80)1.39 (1.11-1.76)1.71 (1.21-2.28)123452.77 (1.25-6.13)HU D, e

39、t al. Chin J Intern Med, 2003; 42: 157-161心房颤动抗栓治疗进展低分子量肝素n半寿期较长n可预测性良好的生物利用度（皮下注射高于90%）和清除率（可以每日使用一次或两次）n根据体重调整的抗血栓反应n采用固定剂量而不必进行实验室监测，除非发生了以下特殊情况，如：肥胖、肾功能不全或者妊娠。n低分子量肝素引起血小板减少症的危险性低于肝素。n院外自行注射低分子量肝素是一个很有前途的方法，与择期心律转复联合使用可以减少患者费用。 心房颤动抗栓治疗进展Pre-Randomization Anti-thrombotic MedicationsOAC (%)(n = 3

40、371 )C+A (%)(n = 3335)ASA26.230.1Clopidogrel2.32.6OAC78.075.7心房颤动抗栓治疗进展心房颤动抗栓治疗进展入选情况6706 pts from 522 centers in 31 countriesArgentina301France103Russia257Australia216Germany581Singapore25Austria12Greece 99South Africa98Belgium141Hong Kong30Spain77Brazil246Italy166Sweden125Canada1100Malaysia45Switz

41、erland46Chile 75Mexico71Taiwan40Czech Republic233Netherlands375Turkey17Denmark56Norway77United Kingdom294Finland53Poland641United States 1074Portugal33心房颤动抗栓治疗进展急性房颤导致卒中的溶拴治疗n理论上，房颤时脱落的陈旧血栓栓塞对溶拴药物的效果不好。由于房颤时缺血性卒中的面积大，合并出血的发生率高nNINDS研究亚组分析 t-PA治疗房颤患者的急性卒中n115例急性卒中（ct 证实）3小时内溶栓nt-PA 0.9mg/kg 最大剂量为100m

42、gn安慰剂双盲对照n评价6个月后的功能状态n所有患者均较优，没有关于房颤的亚组分析心房颤动抗栓治疗进展心源性栓塞卒中的特点n心源性卒中的可能性n发生在不同血管床的多发梗塞n既往有体循环栓塞病史n不明原因的脑梗塞心房颤动抗栓治疗进展血栓栓塞性卒中n患病率高n多发性梗死、面积大n易发生出血性卒中n神经功能缺失症状重n死亡率高心房颤动抗栓治疗进展缺血性卒中的急性期治疗心房颤动抗栓治疗进展房颤患者卒中急性期抗凝n房颤患者最初房颤患者最初2周内缺血性卒中的复发率约为周内缺血性卒中的复发率约为5。n临临床床研研究究（IST和和CAST）中中未未发发现现房房颤颤患患者者和和窦窦性性心律患者对抗栓治疗反映有明

43、显区别。心律患者对抗栓治疗反映有明显区别。n肝肝素素在在卒卒中中急急性性期期抗抗凝凝减减少少缺缺血血性性卒卒中中再再发发的的作作用用还还不不确确定定。IST亚亚组组分分析析和和HAEST研研究究的的结结果果不不一一致致，但总体卒中的再发率和功能恢复没有改善。但总体卒中的再发率和功能恢复没有改善。n抗抗凝凝治治疗疗在在减减少少缺缺血血事事件件复复发发的的获获益益被被同同时时增增加加出出血血抵消。抵消。心房颤动抗栓治疗进展缺血性卒中的急性期抗凝Circulation 2007;115;478-534 心房颤动抗栓治疗进展急性期华法林应用的时机n在EAFT研究中，大约100例在缺血性卒中和TIA后的

44、2周内开始口服华法林，并且没有继发出血。（未包括大面积致残，易出血的卒中）n因通常继发出血出现在卒中发生后的12小时到4天，当患者临床和神经系统稳定后尽早开始应用，通常23天，710天可达到稳定的INR。心房颤动抗栓治疗进展nACCP指南建议：应用任何抗凝药物前，均应该经CT或MRI扫描证实确定没有颅内出血并评价缺血的范围。n对梗塞面积大，临床症状恶化，不明原因头痛，常规复查头部CT。 n没有颅内出血并且梗塞范围较小的房颤患者，只要患者血压正常，可以应用华法林，并使INR维持在2-3。n颅内出血患者长期应用华法林？急性期华法林应用的时机心房颤动抗栓治疗进展心室附壁血栓n通常STEMI伴LV附壁

45、血栓，华法林抗凝3个月（INR 2-3）；n3个月时随访超声心动图，附壁血栓仍然存在（新形成、血栓扩大、活动），需延长抗凝治疗。n联合抗血小板?心房颤动抗栓治疗进展感染性心内膜炎n赘生物、感染组织、心腔内的血栓。n急性IE，发生率22-43%。n高危人群，细菌病源学超声发现大赘生物（10mm），形态，原位二尖瓣，活动，密度低二尖瓣多于主动脉瓣n预防病因治疗：迅速和有效的抗生素治疗抗血小板药物能减少赘生物体积没有抗凝治疗的适应证正在应用口服抗凝治疗者，改用肝素心房颤动抗栓治疗进展其他心源性卒中的预防n主动脉弓动脉粥样硬化病变相关的卒中患者，抗血小板治疗。（1C+）n原因不明缺血性卒中患者，如果合

46、并卵圆孔未闭，推荐抗血小板治疗；（1C+）n 有TIA或卒中病史的二尖瓣脱垂患者，建议抗血小板治疗。（1C+） n人工瓣膜置换术后，华法林抗凝（INR2.5-3.5），根据瓣膜的位置和种类。ACCP 2004抗栓和溶栓指南心房颤动抗栓治疗进展Risk factors for AF patients on warfarin：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1心房颤动抗栓治疗进展NHLBI Randomized ControlledTria

47、l: 2008-2011nPrimary Endpoint:nPercent of Time in Therapeutic Range (PTTR)nHypothesis:n60% PTTR in standard arm versusn 72% PTTR in Genetics Plus ClinicalnNomogram arm心房颤动抗栓治疗进展RISK FACTORS FOR ANELEVATED INR(Its not all Genetics)nAdvanced Age (one-third dose)nAbnormal Liver FunctionnDecreased Vitam

48、in K Intake (NPO, diarrhea, antibiotics)nAlcohol in BingesnChange in Warfarin PreparationnDrug-drug and drug-food interactions心房颤动抗栓治疗进展BRIDGING TRIAL (N=1,293)nProspective cohort; all receiving long-term warfarin; average age: 72 years; mostly AF patientsn 80% had warfarin held 5 daysn 0.7% had thr

49、omboembolism; none had been bridged; 0.4% rate when warfarin was held 5 daysn Of those bridged, 3.7% had major bleed.n(Garcia DA, et al. Arch Intern Med2008; 168: 63-69)心房颤动抗栓治疗进展RISK FACTORS FOR AFnOlder agen Systemic hypertensionn Heart failuren Valvular heart diseasen Diabetes mellitusn Obesity心房

50、颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展Comparison of 12 Risk Stratification Schemes to PredictStroke in Patients With Nonvalvular Atrial Fibrillation(Stroke. 2008;39:000-000.)心房颤动抗栓治疗进展Is There a Critical Value of Daily Atrial Tachyarrhythmia Is There a Critical Value of

51、 Daily Atrial Tachyarrhythmia Burden from Device Diagnostics that Raises Stroke Burden from Device Diagnostics that Raises Stroke Risk?Risk? The TRENDS Study The TRENDS StudyTaya V. Glotzer, Emile G. Daoud, D. George Wyse, Daniel E. Singer, Michael Ezekowitz, Christopher Hilker, Clayton Miller, Dong

52、feng Qi, Paul D. Ziegler. Taya V. Glotzer MDClinical Assistant Professor of MedicineHackensack University Medical Center心房颤动抗栓治疗进展ResultsThe median value for maximum daily burden in all 30-day windows with non-zero AT/AF was 5.5hAll 30 dayWindows (100%)Zero AT/AF BurdenWindows (76%76%)Any AT/AF Burd

53、en Windows (24%24%)Low AT/AF BurdenWindows: Median Burden Value (12%)High AT/AF BurdenWindows: Median Burden Value (12%) 5.5h 5.5h 5.5h心房颤动抗栓治疗进展ResultsAnnualized TE Event RatesAnnualized RateAnnualized Rate (Excluding TIAs)Zero Burden1.1%/Year0.5%/YearLow Burden 5.5 hours2.4%/Year1.8%/Year心房颤动抗栓治疗进

54、展心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展心房颤动抗栓治疗进展华法林的个体差异基因多态性http:/心房颤动抗栓治疗进展华法林维持剂量与体重的关系77例瓣膜置换术后患者中华心血管病杂志2005年2月第33卷第2期心房颤动抗栓治疗进展Dayi Hu, MD, FACC, FHRS Department of CardiologyPeking University Peoples HospitalManagement of AF:A Worldwide Perspective The Chinese Approach心

55、房颤动抗栓治疗进展Balancing Risk and Benefitn? Lower target intensity心房颤动抗栓治疗进展心房颤动抗栓治疗进展VKORC1 gene in Chinese population唐和年，等，中国优生与遗传杂志2007年第15卷第3期心房颤动抗栓治疗进展Per-patient % out-of range INRsAnderson JL et al. Circulation 2007; 116: 2563-2570心房颤动抗栓治疗进展Benefits vs Barriers of POCTBenefits of POCSimplifies anti

56、coagulation management1 Immediate and accurate INR results2 Provider communicates results and dosage adjustments directly to patient2 May improve patient outcomes Face-to-face instruction may improve quality of care Improves business and office efficiency by avoiding2,3 Venous draw Proper handling o

57、f sample Sending to central laboratory for testingAllows more frequent testing Longer TTR may improve patient outcomes Ability to detect INR changes may allowdetection prior to clinically significant event Enhances patient involvement in own care Provides consistency of instrumentationand reagentsBa

58、rriers to PST/PSMLack of physician awareness oracceptance1,2 Fear it will lead to unintendedself-management3 Implementation of PST/PSM3 Reimbursement3心房颤动抗栓治疗进展Hospitalized Patients with AF in China: Causes and Associated ConditionIdiopathic AFRVDCHFCAD Advanced age040%50%60%30%20%10%58.1%40.3%Hyper

59、tensioncaidiomyopathy34.8%33.1%23.9%7.4%5.4%4.1%DiabetesCAD: coronary artery disease; CHF: congestive heart failure; RVD: rheumatic valve disease Chinese J Cardiol, 2003；31：913-916心房颤动抗栓治疗进展Prevalence of Stroke in Chinese Patients with AF %12.95%24.81%17.5%Hu D, 2004Qi W, 200305%10%15%20%25%Hu D, 20

60、04Hu D, et al. 2004 Chin J Intern Med; in press. Random sample of populationQi W, et al. 2003 Chin J Cardiol; 31: 913-916. Case-control study. Hospitalized patientsHu D, et al. 2003 Chin J Intern Med; 42: 157-161. Case-control study. Hospitalized patients心房颤动抗栓治疗进展Risk Factors for Stroke in Chinese

61、with Non Vascular AF: A Case-control StudyAGE 76 yrsHypertensionDiabetesLA thrombiSBP1.76 (1.08-2.89)1.52 (1.28-1.80)1.39 (1.11-1.76)1.71 (1.21-2.28)123452.77 (1.25-6.13)HU D, et al. Chin J Intern Med, 2003; 42: 157-161心房颤动抗栓治疗进展Variable Dose ResponsenGenetic polymorphisms:cytochrome P450 CYP2C9 and

62、 VKORC1 (vitamin K epoxide reductase complex 1)nDisease States, e.g., CHF, malignancynPharmacodynamic changes with aging心房颤动抗栓治疗进展 Age Age 40-8040-80ASPIRIN150-160mgWARFARININR 2.0-3.0Secondary endpoit: lacunar infarction, peripheral arteries embolism, TIA, silent stroke, acute myocardial infarction

63、,serious bleeding NVAF PatientsRandomizeRandomize(n =828)(n =828)Primary endpoint: Death or ISStudy DesignOpen labelThe Randomized Clinical Trial Compared Aspirin with Dose- adjusted Warfarin in NVAF Patients 18 hospitals from 7 provinces in China心房颤动抗栓治疗进展Results Adverse Events- HemorrhageEvent Rat

64、e (% )Event Rate (% )MajorMajorBleedingBleedingMajor + MinorMajor + MinorBleedingBleedingP0.05P0.056.86%6.86%2.44%2.44%0.0%0.0%1.49%1.49%0.0%0.0%0.89%0.89%ICHICH心房颤动抗栓治疗进展CYP2C9n9 trials, n=2775nLow dose and high bleeding risk Gene Doses reduced*（mg/d） Risk of bleeding (OR)CYP2C9*2 0.85(0.601.11) 17

65、% 1.91 (1.163.17) CYP2C9*3 1.92 (1.372.47 ) 37% 1.77 (1.072.91CYP2C9*2/*3 1.47 (1.241.71) 27% 2.26 (1.363.75) HuGEnet systematic review and meta-analysis, Genet Med 2005:7(2):97104.心房颤动抗栓治疗进展心源性栓塞的常见病因q 心房颤动q 二尖瓣狭窄或机械瓣膜置换q卵园口未闭q 近期心肌梗死q 左室附壁血栓q 心房粘液瘤q 扩张性心肌病q 感染性心内膜炎或 非细菌性心内膜炎q主动脉斑块心房颤动抗栓治疗进展Miyasak

66、a et al，JACC Vol. 49, No. 9, 2007心房颤动抗栓治疗进展心房颤动患病率中国及其他地区5.5%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, Aus

67、tralia, triennial 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 ECG0.1%5.1%3.7%3.0%2.8%2.4%1.5%1.3%1.3%0.77%0.60%0.28%8 百万百万 中国房颤患者中国房颤患者心房颤动抗栓治疗进展2008心房颤动抗栓治疗进展