本文選題：急性冠狀動脈綜合征 + 經(jīng)皮冠狀動脈介入術(shù)　； 參考：《青島大學(xué)》2017年碩士論文

【摘要】：目的:觀察急性冠狀動脈綜合征(ACS)患者根據(jù)CYP2C19基因型個體化應(yīng)用抗血小板藥物及劑量進(jìn)行治療,行經(jīng)皮冠狀動脈介入治療(PCI)后6個月,對比其血小板反應(yīng)性和主要心臟不良事件(MACE)及出血事件的發(fā)生,為抗血小板藥物的個體化治療提供參考。方法:入選294例ACS患者,根據(jù)CYP2C19基因型分為快代謝組(CYP2C19*1/*1)、中代謝組(CYP2C19*1/*2,CYP2C19*1/*3)、慢代謝組(CYP2C19*2/*2,CYP2C19*3/*3,CYP2C19*2/*3),快代謝組給予常規(guī)雙聯(lián)抗血小板(氯吡格雷75mg qd+阿司匹林100mg qn)治療方案,中代謝組給予氯吡格雷劑量加倍(氯吡格雷150mg qd+阿司匹林100mg qn)或用新型抗血小板藥物(替格瑞洛90mg bid+阿司匹林100mg qn)治療方案,慢代謝組給予新型抗血小板藥物(替格瑞洛90mg bid+阿司匹林100mg qn)治療方案,比較各組用藥6月后血栓彈力圖(TEG)檢測血小板抑制率變化情況及MACE的發(fā)生情況。結(jié)果:294例ACS患者中,攜帶缺失功能等位基因(CYP2C19*2,CYP2C19*3)的發(fā)生比例與既往研究無差別,快代謝型占42.18%、中間代謝型占41.49%,慢代謝型占16.33%。男性中快代謝型占42.26%(101/239),中代謝型占41.84%(100/239),慢代謝型占15.90%(38/239);女性中快代謝型占41.82%(23/55),中代謝型占40.00%(22/55),慢代謝型占18.18%(10/55)。不同性別的基因型分布無統(tǒng)計學(xué)意義(P0.05)。根據(jù)CYP2C19基因型和個體化抗血小板用藥所分組臨床基線資料及PCI結(jié)果無統(tǒng)計學(xué)差異。中代謝型中氯吡格雷加量組、中代謝型中用新型抗血小板藥物(替格瑞洛)、慢代謝組用新型抗血小板藥物(替格瑞洛)患者用藥六個月后血小板抑制率均較常規(guī)治療方案升高,且ADP均大于30%,差別有統(tǒng)計學(xué)意義,其中,慢代謝組用新型抗血小板藥物(替格瑞洛)的患者和中代謝型組中用新型抗血小板藥物(替格瑞洛)的患者ADP抑制率升高較中代謝型組中氯吡格雷加倍組患者明顯,且六個月后四組的主要心臟不良事件無統(tǒng)計學(xué)意義。結(jié)論:攜帶CYP2C19*2,CYP2C19*3功能缺失基因的高危ACS患者采用氯吡格雷劑量加倍或新型抗血小板藥物(替格瑞洛)與無攜帶CYP2C19*2,CYP2C19*3功能缺失基因的ACS患者采用常規(guī)雙聯(lián)抗血小板治療相比,抗血小板效力和安全性相同。攜帶CYP2C19*2,CYP2C19*3功能缺失基因的高�；颊卟捎眯滦涂寡“逅幬�(替格瑞洛)可充分抑制血小板,不增加出血風(fēng)險,達(dá)到無攜帶缺失等位基因的低�；颊咚�。CYP2C19基因分型為中代謝型的患者采用新型抗血小板藥物(替格瑞洛)或氯吡格雷劑量加倍均可有效抑制血小板反應(yīng)性,主要心臟不良事件發(fā)生率無統(tǒng)計學(xué)差異。CYP2C19基因分型中中代謝和慢代謝所占比例較大,按CYP2C19基因分型進(jìn)行抗血小板藥物的個體化治療很有必要。CYP2C19基因分型可為ACS患者抗血小板藥物的選擇提供參考。
[Abstract]:Objective: to observe the individual use of antiplatelet drugs and dosage in patients with acute coronary syndrome (ACS) according to CYP2C19 genotypes, 6 months after percutaneous coronary intervention (PCI). The platelet reactivity, major adverse cardiac events (MACEE) and bleeding events were compared in order to provide reference for individualized treatment of antiplatelet drugs. Methods: 294 patients with ACS were divided into two groups according to their CYP2C19 genotypes: fast metabolic group (CYP2C19 / 1 / 1 / 1), middle metabolic group (n = 2) with CYP2C19 / 1 / 1 / 1 / 3, slow metabolic group (n = 3) with CYP2C19 / 2 / 2 / 2 / CYP2C192P / 3, fast metabolic group with routine dual antiplatelet (75mg QAD) 100mg Qnn regimen. In the middle metabolic group, the dosage of clopidogrel was doubled (clopidogrel 150mg QD aspirin 100mg QN) or a new antiplatelet drug (tigrilol 90mg bid aspirin 100mg QN) was used. The slow metabolism group was treated with a new antiplatelet drug (tigrilol 90mg bid aspirin 100mg qnn). The changes of platelet inhibition rate and the incidence of MACE were compared after 6 months of treatment with thromboelastography. Results there was no difference in the incidence of CYP2C192C193with CYP2C192C193in 294 ACS patients. Fast metabolic type accounted for 42.18%, intermediate metabolic type 41.49 and slow metabolic type 16.33%. The rate of rapid metabolism was 42.26% of 101 / 239% in men, 41.84% of 100 / 239%, 15.90% of 38 / 239% of slow metabolic type, 41.82% of 23 / 55% of female metabolic type, 40.002% of 22 / 55% of moderate metabolic type, 18.18% 1055% of slow metabolic type. There was no significant difference in genotype distribution among different genders (P0.05). There was no significant difference in clinical baseline data and PCI results according to CYP2C19 genotypes and individual antiplatelet drug groups. The platelet inhibition rate of the patients treated with clopidogrel in the middle metabolic type, the patients with the new antiplatelet drug (tigrilol) in the middle metabolic type (tigrilol), and the slow metabolism group with the new antiplatelet drug (tigrilol) were all higher than that of the routine treatment regimen. And the ADP is greater than 30, the difference is statistically significant, The inhibition rate of ADP in slow metabolic group was significantly higher than that in clopidogrel double group. There was no significant difference in major adverse cardiac events in the four groups after 6 months. Conclusion: high risk ACS patients with CYP2C192C19C193 deletion gene were treated with double dose clopidogrel or a new antiplatelet drug (tigrilol) compared with ACS patients without CYP2C192CYP2C19C193 deletion gene. Antiplatelet efficacy and safety are the same. High-risk patients with CYP2C192-CYP2C193-deletion gene were treated with a new antiplatelet drug (tigrilol) to fully inhibit platelets without increasing the risk of bleeding. Low risk patients with no deletion alleles. Patients with intermediate metabolic type CYP2C19 genotyped by new antiplatelet drugs (tigrilol) or clopidogrel could effectively inhibit platelet reactivity. There was no statistical difference in the incidence of major adverse cardiac events. In the genotyping of CYP2C19, metabolism and slow metabolism accounted for a large proportion. Individualized treatment of antiplatelet drugs according to CYP2C19 genotyping is very necessary. CYP2C19 genotyping can provide reference for the selection of antiplatelet drugs in ACS patients.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R541.4

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本文編號：1836388