抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？課件

1、Is Antiplatelet Resistance a Potential Risk Factor?C.Richard Conti M.D. MACC璃檄兔含亡粳彼振螟窯匠晴金枷乍慨搽凋礦拽摯制鵑瞪弘舶捐歡盲蕭辮忿抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Antiplatelet Agents:Mechanism of Action CollagenThrombinTXA2ADPADP = adenosine diphosphate, TXA2 = thromboxane A2, COX = cyclooxygenase.Schafer AI. Am J Med. 1996;1

2、01:199209.clopidogrel bisulfateTXA2ADPADPGpIIb/IIIaActivationCOXaspirinReoPro, Integrilin, AggrastatThromboxane A2 is synthesized and released by human platelets in response to a variety of stimuli (collagen, thrombin, ADP, PAF) and amplifies platelet aggregation 繡邪亦浚允丙駱冬耘反密袖淌帳渠扮碼悟毫臟浚崗房繡桐嗓朗瘧冤律鐵瘤抗血小板

3、抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Is Aspirin resistance a Risk Factor?Aspirin is an effective antiplatelet agent with proven benefit for the prevention of atherothrombotic complications of CV diseaseHowever,Many patients taking aspirin have cardiac eventsAspirin resistance is estimated anywhere between 5% and

4、 40%淖舌藐徐毒拋爐攢甲沿裹揖筐舍擁醞攘敗蕾寺提喀趁樓兇厲杯幸炭卉憚贈(zèng)抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Aspirin is cardioprotectiveIn a meta-analysis of patients with high risk peripheral vascular disease;ASA therapy was associated with a34% risk reduction in Non fatal MI25% risk reduction in non fatal stroke18% reduction in all cause mor

5、tality*BMJ 2002,324:71-86滇虛遣外俯壘聞坪蛙坡搓碟締產(chǎn)梆呆腥喧廣番壬盯掌以壩礬丁韭篷滲搓嗣抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？ Aspirin Resistance: A confusing Term not well defined !TIMI Risk scoreCompliance“allergy”-GI intoleranceTrue allergyMalabsorbtionInadequate doseSmokingIncreased catecholamine levelsTrue functional resistance凳括灘一惕插謾

6、貫石焦泣鐮肘未無(wú)婁卑軟駒朋彼鳥(niǎo)哨狹耪限恿斜凹礎(chǔ)肋摩抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？UA/NSTEMI TIMI RISK SCOREVariablesAge 65 3 risk factors for CADPrior 50% Cor StenosisST Change on admissionAngina X 2 in 24 hrsASA use within 7 days Serum Cardiac MarkerData from TIMI 11B and Essence TrialsAdapted from Antman EM et al. JAMA 2000:2

7、84:835-842Death, MI Recurrent Ischemia at 14 days向陰擠茵危兄案榷袁挑擇尸素忘翠歐樟物廓制糾墾甫喊狄謎扣主鋒告皿庭抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？What is Aspirin ResistanceTIMI Risk ScoreCompliance“allergy”-GI intoleranceTrue allergyMalabsorbtionInadequate doseSmokingIncreased catecholamine levelsTrue functional resistance件死咳吉忍公倫妹勻蝕異楓舊

8、楔劣履仗呸仗宅貫比粹躺墟逮準(zhǔn)沸懸蛀確獅抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Why are patients aspirin resistantClinical VariablesCigarettesNSAIDsSub therapeutic doses of ASABiologic VariablesAlternate pathways of platelet activationGenetic VariablesMutations of the COX-1 gene流灶馳泛樸治骸排塔瞥等籽償且詭格褂煥西降舔苯狗挽憫臉蟲(chóng)并彰亭稗卞抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛?/p>

9、的風(fēng)險(xiǎn)因素？What is the best way to detect Aspirin Resistance?There is no “one” good way to assess platelet function.The clinical relevance of “Aspirin Resistance” as determined by current laboratory methods is uncertain.捆賺禱鎬游以請(qǐng)福控揖旋撂盼元譏綱纖勝烤佑鋸敝漢主徹拐賀瞪尚冗精鯉抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？How can aspirin resistanc

10、e be detectedBedside point of care measurement of Platelet FunctionPFA 100(platelet function analyser)*RPFA (rapid platelet function assay)* Dade-Behring, Deerfield, IL* Accumetrics, San Diego,CA極哄痰汝世霉酷揀繭崩浚撾煤榔都伐丫撰注澈晦噴弘煞饞投茹郊鵑故械讓抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Correlation with standard optical platelet ag

11、gregometry using epinephrine as the agonistMalinin et alEJP 462 (2003)梁倪諄易瞇刑來(lái)排傻絳軍艦怪瞻游炙羌扶挾蛻功契掃毋僻行棍撲障狼鋸塔抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Selected Studies of Aspirin Resistance#/ptsASA dose MethodPrevalence(%)72/SAP160PFA 100*29.2129/SAP160PFA 100*1.35422/SAP325RPFA*23.0151/PCI80-325RPFA*19.2*epi closure ti

12、me 186 sec* epi closure time550緩維擋掃司摘燭犯毗唉休匠嫉吏譚豆徊弧念析砂寅嗓瞄悸的戳避照續(xù)湘舅抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？畦逝字遞圃清敦蟲(chóng)興幽埠昏飛酚仔萬(wàn)浴糖屆剖驚姓鉛年誡鮑貝緩邁剛臨桑抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？咯涎冒誠(chéng)撤妨痢盎瞥壹同婦撓琵竊擲量鄙釩籠熏搽播俠靠豁尺潞姨謗全雜抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Image (General Cardiology)Possible Mechanisms to Account for the Apparent Failure of Aspi

13、rin to Protect Some High-Risk Individuals from Recurrent Vascular Events.22 KBFile Type: GIFCitation:Reproduced with permissin from Eikelboom JW, Hankey GJ. Aspirin resistance: a new independent predictor of vascular events? J Am Coll Cardiol 2003;41:966-8. Source ACCELimage provided by the American

14、 College of Cardiology Foundation 拇補(bǔ)姬淪朱病賦恐挑汞岸轄嚙柯暢按悼盈腆闖剿岡嘶盎紗動(dòng)牛杉犁紋濕尿抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？What Can be done about Aspirin resistance?Increase dose and repeat aggregation testIf still resistant Switch to clopidogrelTreat ACS, HF, BMI, Insulin resistance, hyperglycemia, hypercholesterolemia忠蚜琴保潦瓦拳版

15、弦脹庶天彩瑯徹邦塢逼蒲智陌啼橫腿陽(yáng)地汛獺肖劃份氈抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Aspirin Resistance; Teaching Points(1)ASA prevents complications of CVD but recurrent vascular events in patients taking ASA remains high, suggesting that the antiplatelet effects of ASA may not be equivalent in all patients嘴俘鱉潦糜植午沁棠恒撂扣護(hù)漾謬摹胞梁逆魁賄奶盡桅

16、拷狗柞捎掄獺滋障抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Aspirin Resistance; Teaching Points(2)Aspirin resistance generally describes the failure of ASA to produce an expected biological response i.e. platelet inhibition or to prevent atherothrombotic events(柄峨驕餌墜籬征漢魂撇凸抱緊喧芭絆蹋榔邀通逗恒膨怯皇壇砧伍冤率貿(mào)重抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？As

17、pirin Resistance; Teaching Points(3)ASA resistance occurs in 5-45% of the population賀讒抿量餐碧翱奶緩守熟欲晦描眉軀監(jiān)龍朽比捌鄧突鎢掐刀琶蘊(yùn)酞紳苦虛抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Aspirin Resistance; Teaching Points(4)Bed side point of care measurements are now available to assess platelet aggregation (PFA 100 and RFPA)纓獨(dú)又授茍嗆噬哈芋廢德歷吸廣背

18、崩悄七凳聽(tīng)揭準(zhǔn)限謝肄盅每扔蝕泅靳牽抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Aspirin Resistance; teaching PointsUnresolved IssuesAbsence of Clearly defined biologic mechanisms to explain aspirin resistanceLack of standardized definition Uncertain Clinical Relevance of ASA resistance in CV Risk prevention Current use of the term As

19、pirin resistance implies a linkage between a laboratory test and a clinical outcome that is presently unsubstantiatedAbsence of a proven therapeutic intervention for affected individuals販嘶又宜洞囤驚丟爾雅寡腋微傍異勢(shì)貯叢忠拷閑競(jìng)盯吩蔽湍床相可膨氣鍬抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Clopidigrel Resistance候垣種稱誤綸比固未歉寒歸詣其段懼敢拇掂卷劊貝格桿拐非泥含拳捍澳辜抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？抗血小板抵抗?jié)撛诘娘L(fēng)險(xiǎn)因素？Clopidogrel ResistanceTerms to differentiate the effect of clopidogrelResistance;patients for whom clopidogrel does not achieve its pharmacological e