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Impact of proton pump inhibitors on efficacy of antiplatelet strategies with ticagrelor or aspirin after percutaneous coronary intervention: Insights from the GLOBAL LEADERS trial: Insights from the GLOBAL LEADERS trial

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Title: Impact of proton pump inhibitors on efficacy of antiplatelet strategies with ticagrelor or aspirin after percutaneous coronary intervention: Insights from the GLOBAL LEADERS trial: Insights from the GLOBAL LEADERS trial
Authors: Masafumi Ono, Yoshinobu Onuma, Hideyuki Kawashima, Hironori Hara, Chao Gao, Rutao Wang, Neil O'Leary, Edouard Benit, Luc Janssens, Maurizio Ferrario, Aleksander Żurakowski, Marcello Dominici, Kurt Huber, Paweł Buszman, Scot Garg, Joanna J. Wykrzykowska, Jan J. Piek, Peter Jüni, Christian Hamm, Stephan Windecker, Pascal Vranckx, Efthymios N. Deliargyris, Deepak L. Bhatt, Robert F. Storey, Marco Valgimigli, Patrick W. Serruys
Contributors: Ono, Masafumi/0000-0002-3919-5648, Gao, Chao/0000-0002-0390-8060, Storey, Robert/0000-0002-6677-6229, Ono, Masafumi, Onuma, Yoshinobu, Kawashima, Hideyuki, Hara, Hironori, Gao, Chao, Wang, Rutao, O'Leary, Neil, BENIT, Edouard, Janssens, Luc, Ferrario, Maurizio, Zurakowski, Aleksander, Dominici, Marcello, Huber, Kurt, Buszman, Pawel, Garg, Scot, Wykrzykowska, Joanna J., Piek, Jan J., Juni, Peter, Hamm, Christian, Windecker, Stephan, VRANCKX, Pascal, Deliargyris, Efthymios N., Bhatt, Deepak L., Storey, Robert F., Valgimigli, Marco, Serruys, Patrick W.
Source: Catheter Cardiovasc Interv
Ono, Masafumi; Onuma, Yoshinobu; Kawashima, Hideyuki; Hara, Hironori; Gao, Chao; Wang, Rutao; O'Leary, Neil; Benit, Edouard; Janssens, Luc; Ferrario, Maurizio; Żurakowski, Aleksander; Dominici, Marcello; Huber, Kurt; Buszman, Paweł; Garg, Scot; Wykrzykowska, Joanna J; Piek, Jan J; Jüni, Peter; Hamm, Christian; Windecker, Stephan; ... (2022). Impact of proton pump inhibitors on efficacy of antiplatelet strategies with ticagrelor or aspirin after percutaneous coronary intervention: Insights from the GLOBAL LEADERS trial. Catheterization and cardiovascular interventions: official journal of the Society for Cardiac Angiography & Interventions, 100(1), pp. 72-82. Wiley 10.1002/ccd.30217 <http://dx.doi.org/10.1002/ccd.30217>
Publisher Information: Wiley, 2022.
Publication Year: 2022
Subject Terms: Ticagrelor, proton pump inhibitor, FOCUSED UPDATE, Myocardial Infarction, 610 Medicine & health, Coronary Artery Disease, THERAPY, DEFINITIONS, 03 medical and health sciences, Percutaneous Coronary Intervention, 0302 clinical medicine, Humans, ticagrelor monotherapy, RISK, drug interaction, OUTCOMES, Aspirin, percutaneous coronary intervention, OMEPRAZOLE, Proton Pump Inhibitors, dual antiplatelet therapy, 3. Good health, Treatment Outcome, CLOPIDOGREL, PLATELET INHIBITION, CLINICAL-TRIALS, Platelet Aggregation Inhibitors
Description: BackgroundSeveral studies have suggested that proton pump inhibitors (PPIs) may reduce the antiplatelet effects of clopidogrel and/or aspirin, possibly leading to cardiovascular events.AimsWe aimed to investigate the association between PPI and clinical outcomes in patients treated with ticagrelor monotherapy or conventional antiplatelet therapy after percutaneous coronary intervention (PCI).MethodsThis is a subanalysis of the randomized GLOBAL LEADERS trial, comparing the experimental antiplatelet arm (23‐month ticagrelor monotherapy following 1‐month dual antiplatelet therapy [DAPT]) with the reference arm (12‐month aspirin monotherapy following 12‐month DAPT) after PCI. Patient‐oriented composite endpoints (POCEs: all‐cause mortality, myocardial infarction, stroke, or repeat revascularization) and its components were assessed stratified by PPI use as a time‐dependent covariate in patients with the experiment or reference antiplatelet arm.ResultsAmong 15,839 patients, 2115 patients (13.5%) experienced POCE at 2 years. In the reference arm, the use of PPIs was independently associated with POCE (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.12–1.44) and its individual components, whereas it was not in the experimental arm (HR: 1.04; 95% CI: 0.92–1.19; pinteraction = 0.035). During the second‐year follow‐up, patients taking aspirin with PPIs had a significantly higher risk of POCE compared to those on aspirin without PPIs (HR: 1.57; 95% CI: 1.27–1.94), whereas the risk did not differ significantly irrespective of PPI in ticagrelor monotherapy group (HR: 1.03; 95% CI: 0.83–1.28; pinteraction = 0.008).ConclusionsIn contrast to conventional antiplatelet strategy, there were no evidence suggesting the interaction between ticagrelor monotherapy and PPIs on increased cardiovascular events, which should be confirmed in further studies.Clinical Trial RegistrationURL: https://clinicaltrials.gov
Document Type: Article
Other literature type
File Description: application/pdf
Language: English
ISSN: 1522-726X
1522-1946
DOI: 10.1002/ccd.30217
DOI: 10.48350/169687
Access URL: https://pubmed.ncbi.nlm.nih.gov/35500171
https://research.rug.nl/en/publications/edcfd4b0-09f6-42f2-887b-5c110ade4733
https://hdl.handle.net/11370/edcfd4b0-09f6-42f2-887b-5c110ade4733
https://doi.org/10.1002/ccd.30217
https://onlinelibrary.wiley.com/doi/full/10.1002/ccd.30217
https://doi.org/10.1002/ccd.30217
https://pure.amsterdamumc.nl/en/publications/a50a8ca6-bcdb-41a8-9412-aacc3bf63b97
https://doi.org/10.1002/ccd.30217
https://boris.unibe.ch/169687/
http://hdl.handle.net/1942/37465
Rights: CC BY NC
Accession Number: edsair.doi.dedup.....59e013159c43fd6a5e5a2c2173f33413
Database: OpenAIRE
Description
Abstract:BackgroundSeveral studies have suggested that proton pump inhibitors (PPIs) may reduce the antiplatelet effects of clopidogrel and/or aspirin, possibly leading to cardiovascular events.AimsWe aimed to investigate the association between PPI and clinical outcomes in patients treated with ticagrelor monotherapy or conventional antiplatelet therapy after percutaneous coronary intervention (PCI).MethodsThis is a subanalysis of the randomized GLOBAL LEADERS trial, comparing the experimental antiplatelet arm (23‐month ticagrelor monotherapy following 1‐month dual antiplatelet therapy [DAPT]) with the reference arm (12‐month aspirin monotherapy following 12‐month DAPT) after PCI. Patient‐oriented composite endpoints (POCEs: all‐cause mortality, myocardial infarction, stroke, or repeat revascularization) and its components were assessed stratified by PPI use as a time‐dependent covariate in patients with the experiment or reference antiplatelet arm.ResultsAmong 15,839 patients, 2115 patients (13.5%) experienced POCE at 2 years. In the reference arm, the use of PPIs was independently associated with POCE (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.12–1.44) and its individual components, whereas it was not in the experimental arm (HR: 1.04; 95% CI: 0.92–1.19; pinteraction = 0.035). During the second‐year follow‐up, patients taking aspirin with PPIs had a significantly higher risk of POCE compared to those on aspirin without PPIs (HR: 1.57; 95% CI: 1.27–1.94), whereas the risk did not differ significantly irrespective of PPI in ticagrelor monotherapy group (HR: 1.03; 95% CI: 0.83–1.28; pinteraction = 0.008).ConclusionsIn contrast to conventional antiplatelet strategy, there were no evidence suggesting the interaction between ticagrelor monotherapy and PPIs on increased cardiovascular events, which should be confirmed in further studies.Clinical Trial RegistrationURL: https://clinicaltrials.gov
ISSN:1522726X
15221946
DOI:10.1002/ccd.30217