唐熠達(dá)-血小板功能檢測(cè)20160110-version03

1、 NATIONAL CENTER FOR CARDIOVASCULAR DISEASES , CHINA FUWAI HOSPITAL, CHINESE ACADEMY OF MEDICAL SCIENCE 382: 61423 17項(xiàng)以西方人群為主的近期研究 標(biāo)準(zhǔn)化血小板功能檢測(cè)，排除了較老的LTA檢測(cè) Relative risk of stent thrombosis according to platelet reactivity levels. Dniel Aradi et al. Eur Heart J 2015;36:1762-1771 Relative risk of bleed

2、ing events according to platelet reactivity levels. Dniel Aradi et al. Eur Heart J 2015;36:1762-1771 Relative risk of mortality according to platelet reactivity levels. Dniel Aradi et al. Eur Heart J 2015;36:1762-1771 Interaction analysis according to subgroups. 檢測(cè)方法 檢測(cè)方法 藥物 藥物 疾病狀態(tài) 疾病狀態(tài) 影響氯吡格雷反應(yīng)的因素

3、 外在因素 劑量：不同劑量的效應(yīng)不同，對(duì)于中代謝型患者 藥物與藥物之間的反應(yīng)（例如：他汀類） 不同的藥物吸收度 不同的活性代謝產(chǎn)物清除率 內(nèi)在因素 P2Y12受體的數(shù)目或結(jié)合力不同 內(nèi)生ADP水平升高 其他血小板激活途徑活性升高 ? ? ?. 患者是否應(yīng)該區(qū)別對(duì)待？ 不同風(fēng)險(xiǎn)患者治療策略有所不同？ 東亞人群與白種人群是否存在風(fēng)險(xiǎn)差異？ Racial/ethnic differences in the risk for intracranial hemorrhage (ICH) Shen AY, J Am Coll Cardiol, 2007 Ethnic variation in advers

4、e cardiovascular outcomes and bleeding complications (CHARISMA) study. (Am Heart J 2009;157:658-65.) Asian-Americans and Caucasian-Americans with STEMI receiving reperfusion therapy in the National Registry of Myocardial Infarction. Rajendra H . Am J Cardiology,2012 發(fā)生顱內(nèi)出血（ICH）的風(fēng)險(xiǎn)存在種族差異 18 867名確診AF的

5、住院患者（78.5%白種人、8%黑種人、9.5%西班牙裔 、3.9%亞裔） 在所有種族中華法林均與ICH風(fēng)險(xiǎn)增加有關(guān)，但在非白種人中風(fēng)險(xiǎn)更高 Shen AY, J Am Coll Cardiol,2007 年 無(wú)ICH事件的可能性 人種/種族 白種人 黑人 西班牙裔 亞裔 Rajendra H . Am J Cardiology ,2012 國(guó)家心肌梗死注冊(cè)研究中接受再灌注治療的STEMI亞裔與高加索裔 美國(guó)人（n=90 317） 再灌注策略再灌注策略 大出血（大出血（%） 纖溶劑纖溶劑纖溶劑纖溶劑+GP IIb/IIIa 高加索裔美國(guó)人高加索裔美國(guó)人亞裔美國(guó)人亞裔美國(guó)人 CHARISMA研究

6、中出血并發(fā)癥的種族差異 在一項(xiàng)當(dāng)代關(guān)于抗血小板治療的試驗(yàn)中確定種族因素是否是心血管事件 及出血并發(fā)癥的一個(gè)獨(dú)立預(yù)測(cè)因素 12 502名（80.1%）白人、486名（3.1%）黑人、775名（5.0%）亞裔 和1613名（10.3%）西班牙裔患者 研究顯示種族并非是主要復(fù)合心血管事件的一個(gè)顯著獨(dú)立預(yù)測(cè)因素 亞裔（校正風(fēng)險(xiǎn)比2.21）與黑人（校正風(fēng)險(xiǎn)比3.06）較西班牙裔患者發(fā) 生中度出血并發(fā)癥的可能性更大 發(fā)生率(%) 伯爾尼/鹿特丹 注冊(cè)研究 j-Cypher (日本注冊(cè)研究) AMC (韓國(guó)中心注冊(cè)研究) 0 13 0.0 1 2 3 5 4 2 1.7% 2.3% 2.9% 0.5%0.6

7、% 0.5% 0.8% 1.0% 0.7% 1.2% RCTs 亞洲數(shù)據(jù)顯示東亞人群的支架血栓發(fā)生率較白種人群更低 東亞/中國(guó)人群缺血事件相對(duì)較低，出血風(fēng)險(xiǎn)相對(duì)較高 基于西方人群制定的血小板功能學(xué)指標(biāo)是否適用？ 對(duì)存在HPR患者進(jìn)行強(qiáng)化治療是否增加出血風(fēng)險(xiǎn)？ 利用血栓彈力圖（TEG）指標(biāo)預(yù)測(cè)臨床事件 31mm 治療范圍治療范圍 1 month 293 planned bypass surgery Measurements: Thrombelastography mapping: TEG Hemostasis System ADP-induced platelet-fibrin clot str

8、ength MAADP ADP inhibition rate and AA inhibition rate Statistics: Receiver operating characteristic curve (ROC) analysis for identifying the best discriminatory level of MAADP associated with ischemic and bleeding events Univariate and multivariate Cox survival analysis was performed to evaluate th

9、e predicting value of new cut-offs. Methods Ischemic and bleeding events in total population No.Incidence Ischemic events 4757.58% cardiac death410.65% stent thrombosis, 80.12% myocardial infarction1171.87% ischemic stroke180.29% Target vessel revascularization2914.64% Bleeding (BARC2)152 2.43% Dist

10、ribution of MAADP Patients with bleeding events had lower MAADP, whereas patients with ischemic events had higher values. No significant differences were found with respect of ADP inhibition rate and AA inhibition rate. ROC Curve for Ischemic Events For ischemic events, the cutoff value of MAADP was

11、 45mm Sensitivity: 59% Specificity: 73% AUC=0.622 Sensitivity ROC Curve for Bleeding For bleeding, the cutoff value of MAADP was 34mm Sensitivity: 78% Specificity: 62% AUC=0.710 Population characteristics according to MAADP LPR MAADP45mm n=1944 P value Age 57105896010 0.201 Male1760 (71)1551 (73)127

12、7 (76)0.132 BMI 25.63.226.03.125.93.50.181 Diabetes mellitus 545 (26)595 (28)660 (34)0.001 Hypertension 1615 (77)1657 (78)1516 (78)0.493 Hyperlipidemia 1571 (63)1449 (69)1376 (68)0.134 Current smoker 692 (33)434 (28)544 (28)0.063 Previous MI 725 (33)710 (33)705 (33)0.836 Previous PCI551 (26)540 (25)

13、539 (28)0.193 Previous CABG96 (6.2)92 (7.1)75 (7.0)0.202 Peripheral vascular disease 64 (3.1)55 (2.6)57 (3.5)0.106 Procedural characteristics LPR MAADP45mm n=1944 P value Treated vessel0.133 LM44 (2.1)49 (2.3)45 (2.2) LAD 1096 (52.3)1192 (56.1)1124 (57.8) LCX440 (21) 425 (20)330 (17) RCA545 (26) 467

14、 (22) 486 (25) SVG21 (1.0)18 (0.9)17 (0.9) Lesion type B2/C1599 (76.2)1555 (73.2)1426 (73.4)0.042 Multivessel intervention609 (27.7)591 (27.8)535 (27.5)0.760 Stents per patient 1.871.091.861.091.861.100.118 Total stent length21 162822 173221 14330.893 Radial access1832 (83.4)1796(84.5)1615(83.1)0.56

15、1 Baseline medications LPR MAADP45mm n=1944 P value Clopidogrel regimen 0.882 Loading dose, 300 mg 1520 (72.5) 1570 (73.9)1407 (72.4) Maintenance dose, 75 mg5d786 (37.5)767 (36.1)731 (37.6) Aspirin 100mg2097 (100)2125 (100)1944 (100)1.000 IIb/IIIa inhibitors (Perioperative)170 (8.1)161 (7.6)146 (7.5

16、)0.108 Statin1818 (86.7)1895 (89.2)1761 (90.6)0.625 Calcium-channel blocker 480 (22.9)514 (24.2)418 (21.5)0.081 Proton pump inhibitor 663 (31.6)727 (34.2)612 (31.5)0.028 Survival Analysis for Ischemic Events UnivariateMultivariate HR, 95%CIP valueHR, 95%CIP value HPR (MAADP45mm) 2.71 1.154.63 0.0152

17、.68 1.994.54 0.001 Diabetes mellitus 1.52 1.011.980.0011.32 1.232.100.046 Multivessel disease 1.92 1.894.18 0.0271.20 0.731.980.219 Chronic renal failure 1.68 1.023.360.018 1.46 0.802.670.387 Total stent length 1.02 1.011.040.0041.50 0.912.47 0.117 Survival Analysis for Ischemic Events In Syntax Sco

18、re45 mm was the predictor of Ischemic events (HR: 2.31; 95%CI: 1.6-5.9) In Syntax Score15 group MAADP45 mm was still the predictor of Ischemic events (HR: 2.64; 95%CI: 1.3-6.3) SYNTAX sore subgroup analysisSYNTAX sore subgroup analysis Survival Analysis for Bleeding UnivariateMultivariate HR, 95%CIP

19、 valueHR, 95%CIP value LPR (MAADP34 mm) 2.03 1.054.33 0.0051.80 1.21-4.69 0.001 Age 1.92 1.235.980.0012.32 1.836.100.046 BMI -1.67 1.134.18 0.027-1.20 0.731.980.219 Survival Analysis for Bleeding MAADP34 mm show significant impact on BARC2 bleeding HR: 1.80; 95%CI: 1.21-4.69; P value0.999 飲酒2(20)43(

20、22.1)0.999 CYP2C19 基因型例(%)0.122 快代謝型1(11.1)49(29.5) 中代謝型4(44.4)90(54.2) 慢代謝型4(44.4)27(16.3) 傳統(tǒng)強(qiáng)化方案vs 新型藥物（替格瑞洛） TEG 結(jié)果 洛 強(qiáng)化抗血小板 P值 N=10 N=195 基線 ADP抑制率8.359.2911.339.160.323 MAADP54.37.255.65.70.519 隨訪3個(gè)月 * ADP抑制率52.2535.9120.2620.940.002 MAADP36.019.048.911.70.028 變化值 ADP抑制率43.937.068.9421.860.003

21、MAADP -18.2818.47 -6.6812.180.028 *轉(zhuǎn)服替格瑞洛前，接受強(qiáng)化抗血小板治療時(shí)間平均為2.2個(gè)月。 替格瑞洛 在3個(gè)月隨訪時(shí)，替格瑞 洛組ADP抑制率及MAADP 改善情況優(yōu)于傳統(tǒng)強(qiáng)化治 療組 血小板功能學(xué)檢測(cè)+氯吡格雷代謝基因型指導(dǎo)臨床策略 不同人種 CYP2C19功能缺失等位基因及表型的發(fā)生頻率 Beitelshees AL, et al. Clin Pharmacol Ther. 2011;89:455-9. CYP2C19 LoF 等位基因?qū)ρ“宸磻?yīng)的貢獻(xiàn)：12% 72%的變異：可遺傳 其他未被發(fā)現(xiàn)的遺傳因素 *2頻率*3頻率% IM% PM 高加索人0.140.024%2% 非洲裔美國(guó)人0.180.00830%3.5% 亞洲人0.270.0946%10.0% u阜外醫(yī)院結(jié)果（2012-10至今） 等位基因頻率分布代謝型分布 * Chang M, Dahl ML, Tybring G (1996) Use of omeprazole as a probe drug for CYP2C19 phenotype in Swedish Caucasians: comparison with S- me