Yasushi Ueki, Jonas D Häner, Sylvain Losdat, Giuseppe Gargiulo, Hiroki Shibutani, Sarah Bär, Tatsuhiko Otsuka, Raminta Kavaliauskaite, Vera R Mitter, Fabrice Temperli, David Spirk, Stefan Stortecky, George C M Siontis, Marco Valgimigli, Stephan Windecker, Clemens Gutmann, Konstantinos C Koskinas, Manuel Mayr, Lorenz Räber
{"title":"阿利库单抗与高强度他汀联合使用对急性髓损伤患者血小板反应性和非编码 RNA 的影响:PACMAN-AMI 试验的一项子研究。","authors":"Yasushi Ueki, Jonas D Häner, Sylvain Losdat, Giuseppe Gargiulo, Hiroki Shibutani, Sarah Bär, Tatsuhiko Otsuka, Raminta Kavaliauskaite, Vera R Mitter, Fabrice Temperli, David Spirk, Stefan Stortecky, George C M Siontis, Marco Valgimigli, Stephan Windecker, Clemens Gutmann, Konstantinos C Koskinas, Manuel Mayr, Lorenz Räber","doi":"10.1055/a-2156-7872","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong> The effect of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. We aimed to explore the effect of alirocumab added to high-intensity statin therapy on P2Y12 reaction unit (PRU) among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). In addition, we assessed circulating platelet-derived noncoding RNAs (microRNAs and YRNAs).</p><p><strong>Methods: </strong> This was a prespecified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Patients recruited at Bern University Hospital, receiving DAPT with a potent P2Y12 inhibitor, and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The primary endpoint was PRU at 4 weeks after study drug initiation as assessed by VerifyNow P2Y12 point-of-care assays.</p><p><strong>Results: </strong> Among 139 randomized patients, the majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] in the alirocumab group vs. 69 [94.5%] in the placebo group, <i>p</i> = 0.14). There were no significant differences in the primary endpoint PRU at 4 weeks between groups (12.5 [interquartile range, IQR: 27.0] vs. 19.0 [IQR: 30.0], <i>p</i> = 0.26). Consistent results were observed in 126 patients treated with ticagrelor (13.0 [IQR: 20.0] vs. 18.0 [IQR: 27.0], <i>p</i> = 0.28). Similarly, platelet-derived noncoding RNAs did not significantly differ between groups.</p><p><strong>Conclusion: </strong> Among AMI patients receiving DAPT with a potent P2Y12 inhibitor, alirocumab had no significant effect on platelet reactivity as assessed by PRU and platelet-derived noncoding RNAs.</p>","PeriodicalId":23036,"journal":{"name":"Thrombosis and haemostasis","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effect of Alirocumab Added to High-Intensity Statin on Platelet Reactivity and Noncoding RNAs in Patients with AMI: A Substudy of the PACMAN-AMI Trial.\",\"authors\":\"Yasushi Ueki, Jonas D Häner, Sylvain Losdat, Giuseppe Gargiulo, Hiroki Shibutani, Sarah Bär, Tatsuhiko Otsuka, Raminta Kavaliauskaite, Vera R Mitter, Fabrice Temperli, David Spirk, Stefan Stortecky, George C M Siontis, Marco Valgimigli, Stephan Windecker, Clemens Gutmann, Konstantinos C Koskinas, Manuel Mayr, Lorenz Räber\",\"doi\":\"10.1055/a-2156-7872\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong> The effect of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. We aimed to explore the effect of alirocumab added to high-intensity statin therapy on P2Y12 reaction unit (PRU) among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). In addition, we assessed circulating platelet-derived noncoding RNAs (microRNAs and YRNAs).</p><p><strong>Methods: </strong> This was a prespecified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Patients recruited at Bern University Hospital, receiving DAPT with a potent P2Y12 inhibitor, and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The primary endpoint was PRU at 4 weeks after study drug initiation as assessed by VerifyNow P2Y12 point-of-care assays.</p><p><strong>Results: </strong> Among 139 randomized patients, the majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] in the alirocumab group vs. 69 [94.5%] in the placebo group, <i>p</i> = 0.14). There were no significant differences in the primary endpoint PRU at 4 weeks between groups (12.5 [interquartile range, IQR: 27.0] vs. 19.0 [IQR: 30.0], <i>p</i> = 0.26). Consistent results were observed in 126 patients treated with ticagrelor (13.0 [IQR: 20.0] vs. 18.0 [IQR: 27.0], <i>p</i> = 0.28). Similarly, platelet-derived noncoding RNAs did not significantly differ between groups.</p><p><strong>Conclusion: </strong> Among AMI patients receiving DAPT with a potent P2Y12 inhibitor, alirocumab had no significant effect on platelet reactivity as assessed by PRU and platelet-derived noncoding RNAs.</p>\",\"PeriodicalId\":23036,\"journal\":{\"name\":\"Thrombosis and haemostasis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Thrombosis and haemostasis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1055/a-2156-7872\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/8/18 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Thrombosis and haemostasis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1055/a-2156-7872","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/8/18 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Effect of Alirocumab Added to High-Intensity Statin on Platelet Reactivity and Noncoding RNAs in Patients with AMI: A Substudy of the PACMAN-AMI Trial.
Objective: The effect of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor alirocumab on platelet aggregation among patients with acute myocardial infarction (AMI) remains unknown. We aimed to explore the effect of alirocumab added to high-intensity statin therapy on P2Y12 reaction unit (PRU) among AMI patients receiving dual antiplatelet therapy (DAPT) with a potent P2Y12 inhibitor (ticagrelor or prasugrel). In addition, we assessed circulating platelet-derived noncoding RNAs (microRNAs and YRNAs).
Methods: This was a prespecified, powered, pharmacodynamic substudy of the PACMAN trial, a randomized, double-blind trial comparing biweekly alirocumab (150 mg) versus placebo in AMI patients undergoing percutaneous coronary intervention. Patients recruited at Bern University Hospital, receiving DAPT with a potent P2Y12 inhibitor, and adherent to the study drug (alirocumab or placebo) were analyzed for the current study. The primary endpoint was PRU at 4 weeks after study drug initiation as assessed by VerifyNow P2Y12 point-of-care assays.
Results: Among 139 randomized patients, the majority of patients received ticagrelor DAPT at 4 weeks (57 [86.4%] in the alirocumab group vs. 69 [94.5%] in the placebo group, p = 0.14). There were no significant differences in the primary endpoint PRU at 4 weeks between groups (12.5 [interquartile range, IQR: 27.0] vs. 19.0 [IQR: 30.0], p = 0.26). Consistent results were observed in 126 patients treated with ticagrelor (13.0 [IQR: 20.0] vs. 18.0 [IQR: 27.0], p = 0.28). Similarly, platelet-derived noncoding RNAs did not significantly differ between groups.
Conclusion: Among AMI patients receiving DAPT with a potent P2Y12 inhibitor, alirocumab had no significant effect on platelet reactivity as assessed by PRU and platelet-derived noncoding RNAs.
期刊介绍:
Thrombosis and Haemostasis publishes reports on basic, translational and clinical research dedicated to novel results and highest quality in any area of thrombosis and haemostasis, vascular biology and medicine, inflammation and infection, platelet and leukocyte biology, from genetic, molecular & cellular studies, diagnostic, therapeutic & preventative studies to high-level translational and clinical research. The journal provides position and guideline papers, state-of-the-art papers, expert analysis and commentaries, and dedicated theme issues covering recent developments and key topics in the field.