趙 靜

·新進(jìn)展·

經(jīng)皮冠狀動(dòng)脈介入治療后雙聯(lián)抗血小板治療療程研究進(jìn)展

趙 靜

經(jīng)皮冠狀動(dòng)脈介入治療后雙聯(lián)抗血小板治療可以有效預(yù)防心血管事件的發(fā)生風(fēng)險(xiǎn)，但是也會(huì)帶來出血風(fēng)險(xiǎn)。目前，其最優(yōu)療程仍存在著較大爭(zhēng)議。近年來國(guó)際指南對(duì)該療程的推薦持續(xù)更新，從早期的“一概而論”到近期的多因素考慮。本文通過回顧近年來國(guó)內(nèi)外相關(guān)指南，結(jié)合臨床試驗(yàn)研究，分析討論雙聯(lián)抗血小板治療療程，指出應(yīng)根據(jù)患者具體情況，如支架類型、基礎(chǔ)疾病、出血風(fēng)險(xiǎn)等，在權(quán)衡風(fēng)險(xiǎn)與獲益后，最終做到個(gè)體化、精準(zhǔn)化治療。

急性冠狀動(dòng)脈綜合征；藥物洗脫支架；經(jīng)皮冠狀動(dòng)脈介入；雙聯(lián)抗血小板；金屬裸支架

趙靜.經(jīng)皮冠狀動(dòng)脈介入治療后雙聯(lián)抗血小板治療療程研究進(jìn)展[J].中國(guó)全科醫(yī)學(xué)，2017，20(21)：2679-2682.[www.chinagp.net]

ZHAO J.Recent developments in duration of dual anti-platelet therapy after percutaneous coronary intervention[J].Chinese General Practice，2017，20(21)：2679-2682.

急性冠脈綜合征(ACS)是指冠狀動(dòng)脈下不穩(wěn)定的粥樣硬化斑塊破裂或糜爛引起血栓形成所導(dǎo)致的心臟急性缺血綜合征[1]。對(duì)于合并ACS和藥物治療無效的穩(wěn)定型心絞痛患者，經(jīng)皮冠狀動(dòng)脈介入治療(PCI)是臨床上一種有效的治療手段，但是由于支架的置入，可能會(huì)造成支架內(nèi)血栓。為了預(yù)防支架內(nèi)血栓的發(fā)生，目前臨床上多進(jìn)行雙聯(lián)抗血小板治療(DAPT)，常規(guī)給藥方案為阿司匹林+P2Y12受體抑制劑。但是DAPT在降低支架內(nèi)血栓風(fēng)險(xiǎn)的同時(shí)也帶來了出血風(fēng)險(xiǎn)，而且若DAPT療程不足，已置入支架的患者支架內(nèi)血栓發(fā)生風(fēng)險(xiǎn)更高[2]，所以各國(guó)指南在DAPT療程方面均有嚴(yán)格推薦[3-16]。美國(guó)DAPT試驗(yàn)顯示，對(duì)比DAPT療程12個(gè)月和30個(gè)月，30個(gè)月組支架內(nèi)血栓、不良心腦血管事件、心肌梗死的發(fā)生率低于12個(gè)月組，但是中重度出血發(fā)生率高于后者，因此延長(zhǎng)DAPT療程風(fēng)險(xiǎn)與收益并存[17]。如何平衡血栓和出血的風(fēng)險(xiǎn)，DAPT的療程多久最為適宜？這些問題被全球多國(guó)醫(yī)務(wù)工作者關(guān)注。本文針對(duì)DAPT療程的相關(guān)內(nèi)容進(jìn)行了匯總及分析，期望從中找出最優(yōu)療程方案。

1 各國(guó)指南推薦療程

對(duì)于DAPT療程的長(zhǎng)短，各國(guó)指南也不盡相同，詳見表1[1,3-16]。

2 DAPT療程的變遷

縱觀指南中的DAPT療程[1,3-16]，發(fā)現(xiàn)近年來DAPT療程出現(xiàn)縮短趨勢(shì)，同時(shí)對(duì)患者的心臟疾病類型、置入支架類型、基礎(chǔ)疾病、危險(xiǎn)分級(jí)也日趨細(xì)化，總體上進(jìn)入了個(gè)體化給藥階段。目前針對(duì)DAPT療程的大規(guī)模數(shù)據(jù)試驗(yàn)正在進(jìn)行中[4]。

2.1 支架類型 早年P(guān)CI多用金屬裸支架(BMS)，但是其發(fā)生血管再狹窄的風(fēng)險(xiǎn)高[18]。2002年上市的藥物洗脫支架(DES)由于置入了藥物，可降低血管再狹窄的風(fēng)險(xiǎn)[19]。第一代DES的支架材料為不銹鋼材質(zhì)，所載的抗細(xì)胞增殖藥物為西羅莫司或紫杉醇，但是其支架內(nèi)血栓風(fēng)險(xiǎn)高于BMS。第二代DES則以鈷鉻合金、鉑鉻合金為支架材料，同時(shí)其載藥種類也改進(jìn)為依維莫司，并采用了新型親水性涂層，目的是減少支架局部炎性反應(yīng)、降低再狹窄率和血栓風(fēng)險(xiǎn)。目前各國(guó)指南對(duì)于穩(wěn)定性冠心病患者應(yīng)用DES的DAPT療程推薦要長(zhǎng)于BMS[3-4,7]。

表1 各國(guó)指南中推薦的DAPT療程

注：DAPT=雙聯(lián)抗血小板治療，DES=藥物洗脫支架，BMS=金屬裸支架

但是有研究表明，對(duì)比置入第二代DES和BMS患者的支架內(nèi)血栓發(fā)生率，前者優(yōu)于后者[20]。THIM等[21]研究顯示，置入第一代DES患者DAPT過程中，對(duì)比停用氯吡格雷的療程，2個(gè)月組、3個(gè)月組、3～6個(gè)月組、6～12個(gè)月組不良心血管事件(心血管疾病導(dǎo)致的死亡、心肌梗死、支架內(nèi)血栓)的發(fā)生率依次降低，但是3～6個(gè)月組與6～12個(gè)月組無顯著差異。GILARD等[22]研究顯示，對(duì)于置入第二代DES的患者，其DAPT療程6個(gè)月與24個(gè)月在死亡、心肌梗死、急診靶血管血運(yùn)重建、卒中、嚴(yán)重出血復(fù)合終點(diǎn)事件發(fā)生率方面無顯著差異。上述研究表明，僅通過延長(zhǎng)DAPT療程來降低不良心血管事件風(fēng)險(xiǎn)的考慮未必適宜。

2.2 基礎(chǔ)疾病 出血是長(zhǎng)DAPT療程的最大風(fēng)險(xiǎn)，而避免DAPT患者合并出血的關(guān)鍵是預(yù)防，因此應(yīng)早期進(jìn)行臨床預(yù)后和出血風(fēng)險(xiǎn)的雙評(píng)估。最新美國(guó)《冠心病患者雙抗治療時(shí)程指南》推薦了DAPT評(píng)分表[4]，將患者的年齡、既往病史、支架類型等方面進(jìn)行了分值量化，認(rèn)為≥2分的患者延長(zhǎng)DAPT療程其收益大于風(fēng)險(xiǎn)；同時(shí)指南列出了增加缺血、支架內(nèi)血栓(可考慮延長(zhǎng)DAPT療程)、出血(可考慮縮短DAPT療程)風(fēng)險(xiǎn)的危險(xiǎn)因素?？梢姡瑢?duì)于DAPT的給藥方案已經(jīng)趨于個(gè)體化。

在基礎(chǔ)疾病方面，2011年美國(guó)《經(jīng)皮冠狀動(dòng)脈介入治療指南》[14]推薦既往上消化道出血病史的患者進(jìn)行DAPT的同時(shí)預(yù)防性使用質(zhì)子泵抑制劑(PPI)(推薦類別Ⅰ)，上消化道出血高危患者(如高齡，合用華法林、甾體類抗炎藥、非甾體類抗炎藥，幽門螺桿菌感染)進(jìn)行DAPT的同時(shí)長(zhǎng)期應(yīng)用PPI是有益的(推薦類別Ⅱa)，但是反對(duì)對(duì)所有DAPT患者預(yù)防性使用PPI(推薦類別Ⅲ)。在合并糖尿病的患者中，對(duì)比置入DES患者的DAPT療程(6個(gè)月和12個(gè)月)，12個(gè)月的患者可能獲益更大[23-24]。

糖尿病與血小板活化增加、血小板反應(yīng)性和聚集增強(qiáng)有關(guān)，而這些均是血栓形成的危險(xiǎn)因素。《中國(guó)經(jīng)皮冠狀動(dòng)脈介入治療指南(2016)》[3]對(duì)于特殊疾病患者的DAPT療程也進(jìn)一步細(xì)化：合并糖尿病的患者，DAPT療程推薦≥12個(gè)月，且對(duì)于藥物的選擇也給予了明確推薦(阿司匹林+替格瑞洛)；對(duì)于合并心房顫動(dòng)的患者，根據(jù)非瓣膜病心房顫動(dòng)患者的血栓栓塞危險(xiǎn)評(píng)分系統(tǒng)(CHA2DS2-VAS)和房顫出血評(píng)分系統(tǒng)(HAS-BLED)，推薦不同DAPT療程，HAS-BLED評(píng)分≤2分者推薦口服抗凝藥物+阿司匹林+氯吡格雷≥6個(gè)月(推薦類別Ⅱa)，HAS-BLED評(píng)分≥3分者推薦口服抗凝藥物+阿司匹林+氯吡格雷至少1個(gè)月(推薦類別Ⅱa)。

中國(guó)《急性ST段抬高型心肌梗死診斷和治療指南》[16]和美國(guó)《經(jīng)皮冠狀動(dòng)脈介入治療指南》[14]中，早期對(duì)于穩(wěn)定性冠心病患者PCI后的DAPT療程推薦與ACS并無差異，而近年來國(guó)際上對(duì)于穩(wěn)定性冠心病患者的DAPT療程短于ACS的推薦日趨一致[3-4]。

3 小結(jié)及展望

通過對(duì)近年來國(guó)內(nèi)外指南的回顧，不難看出，DAPT療程仍在優(yōu)化過程中。指南中推薦的療程大多是來源于近年來DAPT臨床大規(guī)模數(shù)據(jù)試驗(yàn)的結(jié)果，但是各國(guó)進(jìn)行的DAPT試驗(yàn)也存在著一定的局限性，如入組人群的選擇、樣本量的大小、支架類型不統(tǒng)一等，盡管如此，當(dāng)前國(guó)際上對(duì)于DAPT療程的認(rèn)識(shí)仍趨于一致[3,7]，均是在綜合考慮患者的基礎(chǔ)疾病、置入支架的類型等因素，并在進(jìn)行風(fēng)險(xiǎn)評(píng)估的基礎(chǔ)上推薦DAPT療程，摒棄一概而論，也不再一味地通過延長(zhǎng)DAPT療程來達(dá)到降低支架內(nèi)血栓風(fēng)險(xiǎn)的目的，而是權(quán)衡風(fēng)險(xiǎn)與獲益后確定該療程。精準(zhǔn)化醫(yī)學(xué)體現(xiàn)在方方面面，隨著支架材質(zhì)、藥物涂層的改進(jìn)以及醫(yī)療技術(shù)的提升，相信DAPT將更加個(gè)體化治療。

本文無利益沖突。

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(本文編輯：崔麗紅)

Recent Developments in Duration of Dual Anti-platelet Therapy after Percutaneous Coronary Intervention

ZHAOJing

DepartmentofPharmacology,TianjinBinhaiNewAreaofTraditionalChineseMedicineHospital,Tianjin300450,China

Dual anti-platelet therapy(DAPT) after percutaneous coronary intervention can be effective in preventing the risk of cardiovascular events,but it also brings the risk of bleeding.At present,the argument of the optimal duration is still controversial.In recent years,the international guidelines recommend continuous updates to the therapy duration,from "one kind of DAPT duration fits all" to multi-factor-based DAPT duration.Based on reviewing the guidelines and the clinical trials associated with DAPT duration at home and abroad,we analyzed and discussed the DAPT duration,and concluded that,it should be vary by the patients′ own special conditions,such as type of stent placed,underlying disease and risk of bleeding,and after balancing the risks and benefits,in order to achieve the effect of personalized and accurate treatment.

Acute coronary syndrome;Drug-eluting stents;Percutaneous coronary intervention;Dual anti-platelet therapy;Bare-metal stents

R 542.2

A

10.3969/j.issn.1007-9572.2017.21.024

2017-02-14；

2017-06-01)

300450 天津市濱海新區(qū)中醫(yī)醫(yī)院藥學(xué)科