新型口服抗凝藥在房顫中的應(yīng)用

1、新型口服抗凝藥在房顫中的應(yīng)用 主要參考文獻(xiàn)：1.50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study.Lancet. 2015;386(9989):154-62.2.Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fi brillation: a Global Burden o

2、f Disease 2010Study. Circulation. 2014; 129: 83747.3.Prevalence and Risk Factors of Atrial Fibrillation in Chinese Elderly: Results from the Chinese Longitudinal Healthy Longevity Survey.Chin Med J (Engl). 2015;128(18):2426-32.4.An epidemiological study on the prevalence of atrial fibrillation in th

3、e Chinese population of mainland China.J Epidemiol 2008;18(5):209-16.5.Cardioembolic stroke in atrial fibrillation-rationale for preventive closure of the left atrial appendage. Korean Circ J. 2009;39(11):443-58.6. Percutaneous left atrial appendage occlusion for patients in atrial fibrillation subo

4、ptimal for warfarin therapy: 5-year results of the PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) Study.JACC Cardiovasc Interv. 2009;2(7):594-600.7.Percutaneous Left Atrial Appendage Transcatheter Occlusion) for prevention of cardioembolic stroke in non-anticoagulation eligible

5、atrial fibrillation patients: results from the European PLAATO study. EuroIntervention. 2010;6(2):220-6.8.Percutaneous closure of the left atrial appendage versus warfarin therapy for prevention of stroke in patients with atrial fibrillation: a randomised non-inferiority trial. Lancet. 2009;374(9689

6、):534-42.9.Safety of percutaneous left atrial appendage closure: results from the Watchman Left Atrial Appendage System for Embolic Protection in Patients with AF (PROTECT AF) clinical trial and the Continued Access Registry. Circulation. 2011;123(4):417-24.10. Left atrial appendage clip occlusion:

7、early clinical results. J Thorac Cardiovasc Surg. 2010;139(5): 1269-74.11.Blockage of a Mechanical Aortic Valve Leaflet with BioGlue: A Case Report.Heart Surg Forum. 2012;15(6):E310-2.12.Comparative validation of a novel risk score for predicting bleeding risk in anticoagulated patients with atrial

8、fibrillation: the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score. J Am Coll Cardiol. 2011;57(2):173-80.13.Patients with atrial fibrillation and a CHA2DS2-VASc score of 1: are they at low or hi

9、gh stroke risk? J Am Coll Cardiol. 2015; 65(14):1395-7.14.The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0-1: a nationwide cohort study.Thromb Haemost. 2012;107(6):1172-9. 主要參考文獻(xiàn)：15.How to Avoid Adverse Events Duri

10、ng Apixaban Therapy in Patients With Atrial Fibrillation.Circ J. 2015;79(12):2539-40.16.Risk of bleeding with 2 doses of dabigatran compared with warfarin in older and younger patients with atrial fibrillation: an analysis of the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial

11、.Circulation 2011;123(21):2363-72 17.Rationale and design of RE-LY: randomized evaluation of long-term anticoagulant therapy, warfarin, compared with dabigatran.Am Heart J. 2009;157(5):805-10, 810.e1-2. 18.Dabigatran versus warfarin in patients with atrial fibrillation.N Engl J Med. 2009;361(12):113

12、9-51. 19.Comparison of dabigatran versus warfarin in diabetic patients with atrial fibrillation: Results from the RE-LY trial.Int J Cardiol. 2015;196:127-31. 20.Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation.Stro

13、ke. 2013;44(7):1891-6. 21.The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study.Circulation. 2013;128(3):237-43. 22.Gastrointestinal Bleeding in Patients With Atrial Fibrillation Treated With Rivaroxaban or Warfarin: ROCKET AF Tr

14、ial.J Am Coll Cardiol. 2015;66(21):2271-81. 23.Rivaroxaban in the Prevention of Stroke and Systemic Embolism in Patients with Non-Valvular Atrial Fibrillation: Clinical Implications of the ROCKET AF Trial and Its Subanalyses.Am J Cardiovasc Drugs. 2015;15(6):395-401. 24.Apixaban In Patients With Atr

15、ial Fibrillation: Patient Characteristics Of The Latin America Cohort From A Multinational Clinical Trial.Value Health. 2015 ;18(7):A809.25.Stroke prevention with rivaroxaban in higher-risk populations with atrial fibrillation.Int J Clin Pract. 2015;69(7):743-56. 26.Efficacy and safety of rivaroxaba

16、n in real-life patients with atrial fibrillation.Expert Rev Cardiovasc Ther. 2015;13(4):341-53. 27.Digoxin use in patients with atrial fibrillation and adverse cardiovascular outcomes: a retrospective analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Ant

17、agonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).Lancet. 2015;385(9985):2363-70. 28.Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.N Engl J Med. 2011;365(10):883-91. 29.REal-LIfe Evidence of stroke prevention in patients with atrial Fibrillation

18、- The RELIEF study.Int J Cardiol. 2015;203:882-884. 主要內(nèi)容 房顫的流行病學(xué)資料房顫的危險(xiǎn)因素 房顫抗凝治療進(jìn)展NOACs在房顫中的應(yīng)用AF房顫的危害 主要內(nèi)容 房顫的流行病學(xué)資料房顫的危險(xiǎn)因素 房顫抗凝治療進(jìn)展NOACs在房顫中的應(yīng)用AF房顫的危害 房顫的流行病學(xué)資料全球房顫患病情況：Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fi brillation: a Global Burden of Disease 2010Study.

19、Circulation 2014; 129: 83747. 房顫的流行病學(xué)資料我國(guó)房顫患病情況：總體發(fā)病率3.5%Prevalence and Risk Factors of Atrial Fibrillation in Chinese Elderly: Results from the Chinese Longitudinal Healthy Longevity Survey.Chin Med J (Engl) 2015;128(18):2426-32. 主要內(nèi)容 房顫的流行病學(xué)資料房顫的危險(xiǎn)因素 房顫抗凝治療進(jìn)展NOACs在房顫中的應(yīng)用AF房顫的危害 房顫的危險(xiǎn)因素 Title in he

20、re先天性心臟病Title in here種族Title in here年齡1.房顫的發(fā)生與年齡明顯相關(guān)，年齡增長(zhǎng)是房顫發(fā)生的主要原因；2.男性房顫患者多于女性房顫患者，二者比例為1.1:0.8；3.房顫患者中白種人多于黑種人，二者比例為2.2:1.5；4.基礎(chǔ)心臟疾病或相關(guān)疾病：瓣膜病導(dǎo)致的房顫明顯減少，高血壓成為了房顫最常見的危險(xiǎn)因素 獨(dú)立危險(xiǎn)因素Title in here性別Title in here高血壓性心臟病Title in here心功能不全Title in here急性心梗Title in here瓣膜病50 year trends in atrial fibrillation

21、 prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study.Lancet 2015;386(9989):154-62. 主要內(nèi)容 房顫的流行病學(xué)資料房顫的危險(xiǎn)因素 房顫抗凝治療進(jìn)展NOACs在房顫中的應(yīng)用AF房顫的危害 房顫的危害 、 病人生活質(zhì)量下降治療困難，醫(yī)療費(fèi)用高血栓栓塞 心房擴(kuò)大、心力衰竭增加死亡率 心動(dòng)過速性心肌病Left atrial appendage clip occlusion: early clinical results. J Thor

22、ac Cardiovasc Surg. 2010;139(5): 1269-74. 陣發(fā)性房顫持續(xù)性房顫卒中的年發(fā)生率(%)卒中是房顫最常見的并發(fā)癥：非瓣膜性房顫卒中危險(xiǎn)約增加5倍瓣膜病房顫卒中風(fēng)險(xiǎn)約增加17倍卒中是房顫最嚴(yán)重的并發(fā)癥，致殘率高，房顫患者的主要死因；卒中亦可在無癥狀的房顫患者中發(fā)生；即便是接受節(jié)律控制，房顫患者仍然存在較高的卒中風(fēng)險(xiǎn)RACE II = Rate Control Efficacy in Permanent Atrial Fibrillation.Fuster V, et al. J Am Coll Cardiol. 2006;48(4):e149-e246. Ka

23、nnel WB, et al. Med Clin North Am. 2008;92(1):17-42. Page RL, et al. Circulation. 2003;107(8):1141-1145. Hart RG, et al. J Am Coll Cardiol. 2000; 35(1):183-187. Dulli DA, et al. Neuroepidemiology. 2003;22(2):118-123.LowRiskModerateRiskHighRisk1086420.Blockage of a Mechanical Aortic Valve Leaflet wit

24、h BioGlue: A Case Report.Heart Surg Forum. 2012;15(6):E310-2.房顫的危害房顫與卒中房顫抗凝治療核心策略 主要內(nèi)容 房顫的流行病學(xué)資料房顫的危險(xiǎn)因素 房顫抗凝治療進(jìn)展NOACs在房顫中的應(yīng)用AF房顫的危害 房顫抗凝治療進(jìn)展 推薦CHA2DS2-VASc評(píng)分系統(tǒng) 發(fā)現(xiàn)卒中“真正低?！被颊?在抗凝策略中的重要性降低卒中風(fēng)險(xiǎn)關(guān)注重點(diǎn)轉(zhuǎn)變 抗血小板治療新型口服抗凝藥強(qiáng)力推薦 非瓣膜病房顫患者卒中風(fēng)險(xiǎn)評(píng)估 非瓣膜病房顫患者卒中風(fēng)險(xiǎn)評(píng)估 危險(xiǎn)因素評(píng)分充血性心衰/左室功能不全（C） 1高血壓（H） 1年齡75歲（A） 1糖尿?。―） 1卒中/TIA/

25、血栓栓塞（S） 2 總 分 6危險(xiǎn)因素評(píng)分充血性心衰/左室功能不全（C） 1高血壓（H） 1年齡75歲（A） 2糖尿?。―） 1卒中/TIA/血栓栓塞（S） 2血管疾?。╒） 1年齡6574歲（A） 1 性別（女性）（Sc） 1 總 分 9CHADS2評(píng)分CHA2DS2-VASc評(píng)分The value of the CHA2DS2-VASc score for refining stroke risk stratification in patients with atrial fibrillation with a CHADS2 score 0-1: a nationwide cohort

26、study.Thromb Haemost. 2012;107(6):1172-9. 2分者：除外存在禁忌證者推薦OAC治療 主要內(nèi)容 房顫的流行病學(xué)資料房顫的危險(xiǎn)因素 房顫抗凝治療進(jìn)展NOACs在房顫中的應(yīng)用AF房顫的危害新型口服抗凝藥的優(yōu)點(diǎn) 達(dá)比加群酯依度沙班阿派沙班利伐沙班NOACs優(yōu)點(diǎn)：作用迅速，失效快口服劑量相對(duì)固定與食物、藥物相互作用小可預(yù)計(jì)抗凝效果腎臟清除率正常時(shí)勿需監(jiān)測(cè)凝血功能 NOACs在房顫中的應(yīng)用新型口服抗凝藥的藥理學(xué)性質(zhì)比較性質(zhì)達(dá)比加群利伐沙班阿哌沙班依度沙班靶點(diǎn)凝血酶Xa 因子Xa 因子Xa 因子前體藥物是否否否生物利用度6%80%60%50%給藥劑量b.i.d. q.

27、d. b.i.d.q.d.半衰期12-14 h7-11 h12 h9-11 h腎排泄80%33% (66%)25%35%監(jiān)測(cè)否否否否相互作用P-gp3A4/P-gp3A43A4/P-gp起效時(shí)間0.5-2h2-4h1-4h1-4h NOACs在房顫中的應(yīng)用 新型口服抗凝藥的作用機(jī)制XaIIaTF/VIIaXIXIXaVIIIaVaII 纖維蛋白纖維蛋白原TTP889TFPI(tifacogin)NAPc2口服直接Xa因子抑制劑利伐沙班阿哌沙班依度沙班DU-176bYM150注射間接Xa因子抑制劑磺達(dá)肝癸鈉Idraparinux直接凝血酶抑制劑達(dá)比加群APCsTM (ART-123) NOACs

28、在房顫中的應(yīng)用新型口服抗凝藥的相關(guān)期臨床試驗(yàn)藥物作用途徑期臨床試驗(yàn)對(duì)照組研究設(shè)計(jì)研究例數(shù)達(dá)比加群Dabigatran凝血酶抑制劑RELY華法林WarfarinNon-inferiority18113利伐沙班RivaroxabanXa因子拮抗劑ROCKE-AF華法林WarfarinNon-inferiority14264阿哌沙班ApixabanXa因子拮抗劑ARISTOTLE華法林WarfarinNon-inferiority18000依度沙班EdoxabanXa因子拮抗劑ENGAGE華法林WarfarinNon-inferiority16500 NOACs在房顫中的應(yīng)用 直接凝血酶抑制劑達(dá)比加

29、群酯（Dabigatran）商品名：泰畢全劑型：110mg、150mg口服前體藥物強(qiáng)效、可逆性、直接凝血酶抑制劑起效迅速可預(yù)測(cè)抗凝效果較少發(fā)生藥物相互作用，無藥物食物相互作用無需進(jìn)行常規(guī)凝血監(jiān)測(cè) 達(dá)比加群酯在房顫中的應(yīng)用 Dabigatran Compared to Warfarin in 18113 Patients with Atrial Fibrillation at Risk of Stroke達(dá)比加群150mg bid、110mg bid與經(jīng)INR調(diào)整的華法林進(jìn)行非劣效比較其他6%拉美5%亞洲15%北美36%歐洲38%44個(gè)國(guó)家,951個(gè)中心,18113例 達(dá)比加群酯的RE-LY研究

30、 達(dá)比加群酯在房顫中的應(yīng)用RE-LY研究設(shè)計(jì) Atrial fibrillation 1 Risk FactorAbsence of contra-indications951 centers in 44 countriesWarfarinadjusted (INR 2.0-3.0)N=6000Dabigatran Etexilate 110 mg BIDN=6000Dabigatran Etexilate 150 mg BIDN=6000Blinded Event Adjudication.OpenBlinded 達(dá)比加群酯在房顫中的應(yīng)用RDabigatran versus warfarin

31、 in patients with atrial fibrillation.N Engl J Med. 2009;361(12):1139-51. 達(dá)比加群酯150mg顯著降低卒中或全身性栓塞風(fēng)險(xiǎn)年0.00.51.01.52.02.50.010.020.030.050.04累積危險(xiǎn)比0.00華法林達(dá)比加群酯110mgBID達(dá)比加群酯150mgBIDRR 0.90(95% CI: 0.741.10)P0.001 (NI)P=0.29 (Sup)RR 0.65(95% CI: 0.520.81)P0.001 (NI)P0.001 (Sup)RRR 35% 達(dá)比加群酯在房顫中的應(yīng)用Dabigatra

32、n versus warfarin in patients with atrial fibrillation.N Engl J Med. 2009;361(12):1139-51. 達(dá)比加群酯150mg顯著降低缺血性卒中風(fēng)險(xiǎn)缺血性卒中或未明確卒中(100患者-年)n:159/6015111/6076143/6022達(dá)比加群酯110 mg BID達(dá)比加群酯150 mg BID華法林00.51.01.52.01.34%0.92%1.21%RR 1.11 (95% CI: 0.88-1.39)P=0.35 (Sup)RR 0.76 (95% CI: 0.590.97)24%P=0.03 (Sup)

33、達(dá)比加群酯在房顫中的應(yīng)用Dabigatran versus warfarin in patients with atrial fibrillation.N Engl J Med. 2009;361(12):1139-51. 達(dá)比加群酯150mg顯著降低血管性死亡風(fēng)險(xiǎn)血管性死亡(100患者-年)n:289/6015274/6076317/6022達(dá)比加群酯110 mg BID達(dá)比加群酯150 mg BID華法林00.51.01.52.02.43%2.28%2.69%RR 0.90 (95% CI: 0.771.06)P=0.21 (Sup)RR 0.85 (95% CI: 0.720.99)P=

34、0.04 (Sup)15%2.53.0 達(dá)比加群酯在房顫中的應(yīng)用Dabigatran versus warfarin in patients with atrial fibrillation.N Engl J Med. 2009;361(12):1139-51. 亞洲人群卒中或全身性栓塞結(jié)果達(dá)比加群酯150mg bid達(dá)比加群酯110mg bid華法林933923926Subjects at riskDE 150mg bidDE 110mg bid華法林906888886875866858697683664420401382237216198061218243000.020.040.060.0

35、80.10月累積危險(xiǎn)比 達(dá)比加群酯150mg bid HR 0.45 (95% CI: 0.280.72)RRR 55% 達(dá)比加群酯在房顫中的應(yīng)用Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation.Stroke. 2013;44(7):1891-6. 04.0HR 0.57 (p= 0.0079)(95% CI: 0.380.84)2.0% / 年HR 0.57( p= 0.07

36、05)(95% CI: 0.380.85)3.0達(dá)比加群酯150mg bid(39/933)達(dá)比加群酯110mg bid(39/923)華法林(66/926)21.0亞洲人群中兩種劑量達(dá)比加群酯均顯著降低大出血風(fēng)險(xiǎn)43% 達(dá)比加群酯在房顫中的應(yīng)用Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation.Stroke. 2013;44(7):1891-6. 達(dá)比加群酯的RELY-ABLE研究The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study.Circulation. 2013 ;128(3):237-43. 達(dá)比加群酯在房顫中的應(yīng)用 Discovery