Mehmet Melek, Hasan Ari, Alper Karakuş, Selma Ari, Ahmet Tütüncü, Tahsin Bozat
{"title":"静脉硝酸盐治疗对急性冠脉综合征患者氯吡格雷抗血小板作用的影响:一项初步研究。","authors":"Mehmet Melek, Hasan Ari, Alper Karakuş, Selma Ari, Ahmet Tütüncü, Tahsin Bozat","doi":"10.1177/10742484251357147","DOIUrl":null,"url":null,"abstract":"<p><p>BackgroundClopidogrel is a pro-drug that requires metabolic activation by hepatic cytochrome P450 (CYP) enzymes in two steps. Previous studies have shown that the administration of continuous nitrate significantly affects the activity of hepatic CYP. In this pilot study, we assess the impact of intravenous nitrate treatment on the antiplatelet effects of clopidogrel in patients with non-ST-elevation myocardial infarction (NSTEMI).MethodWe included 20 NSTEMI patients: 15 in the nitrate group and five in the control group. All patients received a 300 mg acetylsalicylic acid and a 600 mg clopidogrel loading dose. The nitrate group was administered an intravenous glyceryl trinitrate infusion at 10 µg/min for 48 h. After the drugs were initiated, blood samples were collected from patients at intervals of 30th minutes, 60th minutes, 120th minutes, fourth hour, sixth hour, and 48th hour to assess platelet function. The antiplatelet effect of clopidogrel was evaluated using the platelet reactivity unit (PRU) from the Verify-Now P2Y12 assay.ResultThe PRU values at baseline and the 30th, 60th, 120th minutes, and 48th hour were similar between the two groups (<i>P</i> > .05). However, PRU values at the fourth and sixth hours were significantly higher in the nitrate group than in the control group (274.1 ± 53.9 vs 162.4 ± 39.9; <i>P</i> = .002 and 272.0 ± 67.0 vs 185.6 ± 18.1; <i>P</i> = .03, respectively).ConclusionIntravenous nitrate therapy in patients with NSTEMI delayed the onset of the antiplatelet effect of orally loaded clopidogrel by at least 4 h. This point should be kept in mind in patients using clopidogrel and nitrate therapy together. (NCT06878638).</p>","PeriodicalId":15281,"journal":{"name":"Journal of Cardiovascular Pharmacology and Therapeutics","volume":"30 ","pages":"10742484251357147"},"PeriodicalIF":2.8000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of Intravenous Nitrate Treatment on Antiplatelet Effects of Clopidogrel in Acute Coronary Syndrome Patients: A Pilot Study.\",\"authors\":\"Mehmet Melek, Hasan Ari, Alper Karakuş, Selma Ari, Ahmet Tütüncü, Tahsin Bozat\",\"doi\":\"10.1177/10742484251357147\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>BackgroundClopidogrel is a pro-drug that requires metabolic activation by hepatic cytochrome P450 (CYP) enzymes in two steps. Previous studies have shown that the administration of continuous nitrate significantly affects the activity of hepatic CYP. In this pilot study, we assess the impact of intravenous nitrate treatment on the antiplatelet effects of clopidogrel in patients with non-ST-elevation myocardial infarction (NSTEMI).MethodWe included 20 NSTEMI patients: 15 in the nitrate group and five in the control group. All patients received a 300 mg acetylsalicylic acid and a 600 mg clopidogrel loading dose. The nitrate group was administered an intravenous glyceryl trinitrate infusion at 10 µg/min for 48 h. After the drugs were initiated, blood samples were collected from patients at intervals of 30th minutes, 60th minutes, 120th minutes, fourth hour, sixth hour, and 48th hour to assess platelet function. The antiplatelet effect of clopidogrel was evaluated using the platelet reactivity unit (PRU) from the Verify-Now P2Y12 assay.ResultThe PRU values at baseline and the 30th, 60th, 120th minutes, and 48th hour were similar between the two groups (<i>P</i> > .05). However, PRU values at the fourth and sixth hours were significantly higher in the nitrate group than in the control group (274.1 ± 53.9 vs 162.4 ± 39.9; <i>P</i> = .002 and 272.0 ± 67.0 vs 185.6 ± 18.1; <i>P</i> = .03, respectively).ConclusionIntravenous nitrate therapy in patients with NSTEMI delayed the onset of the antiplatelet effect of orally loaded clopidogrel by at least 4 h. This point should be kept in mind in patients using clopidogrel and nitrate therapy together. (NCT06878638).</p>\",\"PeriodicalId\":15281,\"journal\":{\"name\":\"Journal of Cardiovascular Pharmacology and Therapeutics\",\"volume\":\"30 \",\"pages\":\"10742484251357147\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Cardiovascular Pharmacology and Therapeutics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/10742484251357147\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/7/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Cardiovascular Pharmacology and Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/10742484251357147","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/7/2 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
摘要
氯吡格雷是一种前药,需要肝细胞色素P450 (CYP)酶分两个步骤进行代谢激活。既往研究表明,连续给予硝酸盐可显著影响肝脏CYP活性。在这项初步研究中,我们评估了静脉硝酸盐治疗对非st段抬高型心肌梗死(NSTEMI)患者氯吡格雷抗血小板作用的影响。方法20例NSTEMI患者:硝酸组15例,对照组5例。所有患者均接受300 mg乙酰水杨酸和600 mg氯吡格雷负荷剂量。硝酸组以10µg/min静脉滴注三硝酸甘油48 h。给药后,分别于第30分钟、第60分钟、第120分钟、第4小时、第6小时、第48小时采血,评估患者血小板功能。使用Verify-Now P2Y12试验的血小板反应性单位(PRU)评估氯吡格雷的抗血小板作用。结果两组患者基线及30、60、120、48 h PRU值比较,差异无统计学意义(P < 0.05)。然而,在第4和第6小时,硝酸盐组的PRU值显著高于对照组(274.1±53.9 vs 162.4±39.9;p =。002和272.0±67.0 vs 185.6±18.1;p =。分别为03)。结论NSTEMI患者静脉硝态氮治疗可使口服氯吡格雷抗血小板作用的起效延迟至少4小时。同时使用氯吡格雷和硝态氮治疗的患者应牢记这一点。(NCT06878638)。
Impact of Intravenous Nitrate Treatment on Antiplatelet Effects of Clopidogrel in Acute Coronary Syndrome Patients: A Pilot Study.
BackgroundClopidogrel is a pro-drug that requires metabolic activation by hepatic cytochrome P450 (CYP) enzymes in two steps. Previous studies have shown that the administration of continuous nitrate significantly affects the activity of hepatic CYP. In this pilot study, we assess the impact of intravenous nitrate treatment on the antiplatelet effects of clopidogrel in patients with non-ST-elevation myocardial infarction (NSTEMI).MethodWe included 20 NSTEMI patients: 15 in the nitrate group and five in the control group. All patients received a 300 mg acetylsalicylic acid and a 600 mg clopidogrel loading dose. The nitrate group was administered an intravenous glyceryl trinitrate infusion at 10 µg/min for 48 h. After the drugs were initiated, blood samples were collected from patients at intervals of 30th minutes, 60th minutes, 120th minutes, fourth hour, sixth hour, and 48th hour to assess platelet function. The antiplatelet effect of clopidogrel was evaluated using the platelet reactivity unit (PRU) from the Verify-Now P2Y12 assay.ResultThe PRU values at baseline and the 30th, 60th, 120th minutes, and 48th hour were similar between the two groups (P > .05). However, PRU values at the fourth and sixth hours were significantly higher in the nitrate group than in the control group (274.1 ± 53.9 vs 162.4 ± 39.9; P = .002 and 272.0 ± 67.0 vs 185.6 ± 18.1; P = .03, respectively).ConclusionIntravenous nitrate therapy in patients with NSTEMI delayed the onset of the antiplatelet effect of orally loaded clopidogrel by at least 4 h. This point should be kept in mind in patients using clopidogrel and nitrate therapy together. (NCT06878638).
期刊介绍:
Journal of Cardiovascular Pharmacology and Therapeutics (JCPT) is a peer-reviewed journal that publishes original basic human studies, animal studies, and bench research with potential clinical application to cardiovascular pharmacology and therapeutics. Experimental studies focus on translational research. This journal is a member of the Committee on Publication Ethics (COPE).