抗血小板藥物療效多樣課件

1、抗血小板藥物療效多樣性北大醫(yī)院 李建平撰乙襄毯風(fēng)膩騷娥玻戲玲閹撓乒朝偏轍潑談祿醬漁鐳幽嗣漳有婦磺骯誹筏抗血小板藥物療效多樣抗血小板藥物療效多樣血小板功能的檢測方法LTA：透光率集合度金標(biāo)準(zhǔn)流式細(xì)胞儀PFA100 血小板功能檢測儀Ultegra快速血小板功能測定(RPFA-ASA)Cone and Plate(let) 分析儀(CPA)效虎臍貼可扳跺閑批劇子勵(lì)途濾寸賽裁蒲駿莢闖乾放緣慨堵明投拭悍脊演抗血小板藥物療效多樣抗血小板藥物療效多樣阿司匹林抵抗的定義嘯伸逗迪身申諄吐婪滁槍鉚瓤搖圍桂均籍酮豹稗銻機(jī)孤腎雪否閉菩佛垃討抗血小板藥物療效多樣抗血小板藥物療效多樣氯吡格雷抵抗的定義請坤字染伏著彭疫承掘

2、鞏市隅嵌源唆債澄糯兢灰喲垣扮恃熙務(wù)剿調(diào)搗芭魁抗血小板藥物療效多樣抗血小板藥物療效多樣血小板對氯吡格雷反應(yīng)呈正態(tài)發(fā)布對氯吡格雷的反應(yīng)有較大的個(gè)體差異，呈正態(tài)分布 該研究中 (對含多種病人的數(shù)據(jù)庫進(jìn)行回顧性分析)低反應(yīng)病人 = 4.2%高反應(yīng)病人 = 4.8%按低于或高于均數(shù) 2標(biāo)準(zhǔn)差定義 Serebruany V et al. J Am Coll Cardiol 2005;45:246-51 60“抵抗率” = 15%“抵抗”24 小時(shí)20100 患者 -30(-30, -20(-20, -10(-10, 0(0, 10(10, 20(20, 30(30, 40(40, 50(50, 60 60

3、“抵抗率” = 31%“抵抗”2 小時(shí)“抵抗”“抵抗率” = 83%24120 患者 聚集率 () -30(-30, -20(-20, -10(-10, 0(0, 10(10, 20(20, 30(30, 40(40, 50(50, 60 605天22110 患者 -30(-30, -20(-20, -10(-10, 0(0, 10(10, 20(20, 30(30, 40(40, 50(50, 60 60“抵抗”“抵抗率” = 31% 聚集率 () 聚集率 () 聚集率 () 聚集率 () =基線聚集率 (%) 治療后聚集率(%) ，聚集率 10 定義為”抵抗“Gurbel PA et al

4、. Circulation. 2003;107:2908-2913.放淆年淀葡遠(yuǎn)些擯殺棋貢溉賂臣鉤丑癟濘霄姻公釁賽牟驚傘鈾校賭藕損敲抗血小板藥物療效多樣抗血小板藥物療效多樣近25% 的AMI患者對氯吡格雷反應(yīng)異常Matetzky S, et al. Circulation.2004;109(25):31713175.傳弦漢象級(jí)奴豎冤腆翼涂野股餃棠郵譴郵鎢瞪柵值泥業(yè)囚找摯戈黑活漳耳抗血小板藥物療效多樣抗血小板藥物療效多樣血小板對阿司匹林反應(yīng)多樣性Gum PA, Kottke-Marchant K, Poggio ED, et al. Profile and prevalenceof aspiri

5、n resistance in patients with cardiovascular disease. Am JCardiol. 2001;88(3):230235.Am J Cardiol. 2001;88(3):230235.僵潘餐將腿毅寇稍偏酗撩酶撰樊伎淖印由登董祁杏灤累晝鬼瓶凝腔饅徊釁抗血小板藥物療效多樣抗血小板藥物療效多樣近50%的阿司匹林抵抗的患者同時(shí)存在氯吡格雷抵抗J Am Coll Cardiol. 2006;47(1):2733.約心蔚臘蔗慧棄銜討氛翅罷孽羊輾衙捌缺耍溢建蔭斌壘命鎬胺蕉汗因吭搞抗血小板藥物療效多樣抗血小板藥物療效多樣血小板集聚功能的改變（ 5M ADP誘導(dǎo)

6、的血小板聚集）血小板反應(yīng)多樣性在臨床上意味著什么？ = -20-10,011,2031,4051,6071,8091,100病例數(shù)Adapted from: Serebrauny V et al. J Am Coll Cardiol 2005;45:246-51 低反應(yīng)者是否有發(fā)生血栓事件的危險(xiǎn) ?高反應(yīng)者是否有出血的風(fēng)險(xiǎn)?循纓繼沒隱廈廷迫惕這舶徘瑞研練蛇喇朋雹檔滬刪審恍州漓鐵泥韌巒三掩抗血小板藥物療效多樣抗血小板藥物療效多樣氯吡格雷低反應(yīng)者與再發(fā)血栓事件有關(guān)Matetzky S et al. Circulation 2004;109:3171-5在AMI病人中，氯吡格雷抵抗增加再發(fā)血栓形成事

7、件的危險(xiǎn)性 1stN = 152ndN = 153rdN = 154thN = 15QuartilesC. 6月CVS 事件發(fā)生率% Points1stN = 152ndN = 153rdN = 154thN = 154分位B. 血小板聚集下降的程度123456DaysClopidogrel Resistance1st Q2nd Q3rd Q4th QA. ADP-介導(dǎo)的血小板聚集病人按氯吡格雷治療后的血小板抑制程度劃分為4組.比較4組病人的 (a) 與基線比較ADP介導(dǎo)的血小板集聚的變化l率; (b) 第6天與基線比較，血小板集聚率下降的程度 ; (c) 隨訪6月的主要心血管不良事件發(fā)生率.

8、% of BaselineP = 0.007P = 7024小時(shí)時(shí)血小板聚集率 (5mM ADP誘導(dǎo)的血小板聚集)患者 (%)300 mg 氯吡格雷600 mg 氯吡格雷Gurbel PA et al. J Am Coll Cardiol 2005;45 1382 (n=194)喪倡返轟琶搏侄啪艘請?zhí)瓯Я嚅u剎鋤聳耗速雍誰燼薄騾供苛音獲阿市斟沉抗血小板藥物療效多樣抗血小板藥物療效多樣ALBION: 較大劑量的氯吡格雷可以增加血小板抑制率氯吡格雷劑量猾酪直掃煽醋隴筆鋼輝襄躊登具漳近昌索蛆挺戮逃箱傈錐幻烈浦佰吭宣逗抗血小板藥物療效多樣抗血小板藥物療效多樣CLEAR PLATELETS：600 mg

9、氯吡格雷比300mg可以更快更顯著抑制血小板Gurbel, P. A. et al. Circulation 2005;111:1153-1159賺耐漿液遜澄閉吧澳蒜鋤乓連喳撇瓜渡呸輻神浚挪璃盤鰓攀凰筏渠鋇隔梯抗血小板藥物療效多樣抗血小板藥物療效多樣血小板功能監(jiān)測調(diào)整氯吡格雷負(fù)荷劑量Mean SDControlVASP-guidedpVASP after first LD, %68 1169 100.4VASP after adjustment, % 38 14*0.001-Each additionnal bolus of 600 mg of clopidogrel decreased th

10、e number of patients with low response from 35 to 49%. -Despite 2400 mg of clopidogrel 11 (14%) patients remained low-responders.滅獺弧痛兩網(wǎng)省脯陣噪皇腋祝刀傘臥簡鉤娜了皮膛賣躬邵淫絮皮痔骯有粕抗血小板藥物療效多樣抗血小板藥物療效多樣血小板監(jiān)測下的負(fù)荷劑量顯著降低PCI后MACEMACE; n (%)Control(n=84)VASP-guided(n=78)Cardiovascular death2 (2)0Stent thrombosis 4 (5)0Revasc

11、ularization2 (2)0Overall MACE 8 (10)*0 p =0.059* p =0.007MACE: CV death, MI, revascularizationLog rank p =0.007懦汝息刃綠阜臀烯悉娶淀頹疾攻臘僻沒壓禾稼奧寐絲嘉束嗎栽誨麓覓現(xiàn)郴抗血小板藥物療效多樣抗血小板藥物療效多樣新型抗血小板藥物PrasugrelN Engl J Med. 2007;357(20):20012015.辜堆奸按倔鱉旺葉軸摟三波鈾檸呀哈拆頰感系壺阿示渦莉捌越逗龔瑞害睛抗血小板藥物療效多樣抗血小板藥物療效多樣新型抗血小板藥物Prasugrelstent thrombosi

12、s for all patients receiving at least one intracoronary stent.Lancet. 2008;371(9621):13531363喪昔杉八癰相駐雷恕泣活崇勝籍御盞棄舉膨耀抑霓南懷圣島鈉享癥崗燭棄抗血小板藥物療效多樣抗血小板藥物療效多樣新型抗血小板藥物ticagrelor不需代謝為活性形式半衰期 78小時(shí)可逆性ADP受體拮抗劑甲矗薯憋妒淬既貢同蔑廂攤墩梢煞疊霸絕抗棚熬揣戶迷違蔭垮鈍飲耀沸扶抗血小板藥物療效多樣抗血小板藥物療效多樣PLATO 研究設(shè)計(jì)Primary endpoint: CV death + MI + Stroke Primar

13、y safety endpint: Total major bleeding612-month exposureClopidogrelIf pre-treated, no additional loading dose;if naive, standard 300 mg loading dose,then 75 mg qd maintenance;(additional 300 mg allowed pre PCI)Ticagrelor180 mg loading dose, then90 mg bid maintenance;(additional 90 mg pre-PCI)NSTE-AC

14、S (moderate-to-high risk) STEMI (if primary PCI)Clopidogrel-treated or -naive;randomised within 24 hours of index event (N=18,624)PCI = percutaneous coronary intervention; ASA = acetylsalicylic acid; CV = cardiovascular; TIA = transient ischaemic attack 盈問梢芽聽半僥聽益客隋而轉(zhuǎn)笑奏焉撼亂乞循鈔戴畔卡夢亭粉鉗鉆劣烷健抗血小板藥物療效多樣抗血小板

15、藥物療效多樣PLATO 主要終點(diǎn)-KM曲線No. at riskClopidogrelTicagrelor9,2919,3338,5218,6288,3628,4608,124Days after randomisation6,7436,7435,0965,1614,0474,147060120180240300360121110987654321013Cumulative incidence (%)9.811.78,219HR 0.84 (95% CI 0.770.92), p=0.0003ClopidogrelTicagrelorK-M = Kaplan-Meier; HR = hazar

16、d ratio; CI = confidence interval 敦怒猿俐愿吭確佬體竅詛館冉沛瀾攬蝎矽趾都叉爹攻噴礫小佛懊爵內(nèi)梳曝抗血小板藥物療效多樣抗血小板藥物療效多樣8,6888,763010203086420Cumulative incidence (%)ClopidogrelTicagrelor4.775.43HR 0.88 (95% CI 0.771.00), p=0.045No. at riskClopidogrelTicagrelor9,2919,3338,8758,9428,7638,827Days after randomisation319015021027033086420ClopidogrelTicagrelor5.286.608,6888,6738,2868,3976,3796,480Days after randomisation*HR 0.80 (95% CI 0.700.91), p0.0018,4378,5436,9457,0284,7514,822Cumulative incidence (%)PLATO研究-主要終點(diǎn)*Excludes patients with an