Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial

Introduction Minority populations in the USA are disproportionately affected by cardiovascular conditions. Reduced responsiveness to clopidogrel among carriers of CYP2C19 variants has been reported in patients with either coronary artery disease (CAD) or acute coronary syndrome (ACS) after the percu...

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Main Authors: Dagmar F Hernandez-Suarez, Kyle Melin, Frances Marin-Maldonado, Hector J Nunez, Ariel F Gonzalez, Lorena Gonzalez-Sepulveda, Sona Rivas-Tumanyan, Hetanshi Naik, Gualberto Ruaño, Stuart A Scott, Jorge Duconge
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Language:English
Published: BMJ Publishing Group 2020-08-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/10/8/e038936.full
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author Dagmar F Hernandez-Suarez
Kyle Melin
Frances Marin-Maldonado
Hector J Nunez
Ariel F Gonzalez
Lorena Gonzalez-Sepulveda
Sona Rivas-Tumanyan
Hetanshi Naik
Gualberto Ruaño
Stuart A Scott
Jorge Duconge
author_facet Dagmar F Hernandez-Suarez
Kyle Melin
Frances Marin-Maldonado
Hector J Nunez
Ariel F Gonzalez
Lorena Gonzalez-Sepulveda
Sona Rivas-Tumanyan
Hetanshi Naik
Gualberto Ruaño
Stuart A Scott
Jorge Duconge
author_sort Dagmar F Hernandez-Suarez
collection DOAJ
description Introduction Minority populations in the USA are disproportionately affected by cardiovascular conditions. Reduced responsiveness to clopidogrel among carriers of CYP2C19 variants has been reported in patients with either coronary artery disease (CAD) or acute coronary syndrome (ACS) after the percutaneous coronary intervention (PCI). Previous studies have evaluated CYP2C19 genotyping-guided antiplatelet therapy in selected populations; however, this has yet to be tested among Hispanics. Given the paucity of clinical research on CYP2C19 and antiplatelet clinical outcomes in Hispanics, our study will test the safety and efficacy of a genetic-driven treatment algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics.Methods and analysis This is a multicentre, prospective, non-randomised clinical trial that proposes an assessment of pharmacogenomic-guided DAPT in post-PCI Caribbean Hispanic patients with ACS or CAD. We will recruit 250 patients to be compared with a matched non-concurrent cohort of 250 clopidogrel-treated patients (standard-of-care). Major adverse cardiovascular events (MACEs) such as all-cause death, myocardial infarction (MI), stroke, coronary revascularisation, stent thrombosis and bleedings over 6 months will be the study endpoints. Among the recruited, high-risk patients will be escalated to ticagrelor and low-risk patients will remain on clopidogrel. The primary objective is to determine whether genetic-guided therapy is superior to standard of care. The secondary objective will determine if clopidogrel treatment in low-risk patients is not associated with a higher rate of MACEs compared with escalated antiplatelet therapy in high-risk patients. Patients will be enrolled up to the group’s completion.Ethics and dissemination Approval was obtained from the Institutional Review Board of the University of Puerto Rico Medical Sciences Campus (protocol # A4070417). The study will be carried out in compliance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice Guidelines. Findings will be published in a peer-reviewed journal and controlled access to experimental data will be available.Trial registration number NCT03419325; Pre-results.
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spelling doaj-art-a25cc988e2f8412da95b6ee78b5869842024-12-03T10:50:09ZengBMJ Publishing GroupBMJ Open2044-60552020-08-0110810.1136/bmjopen-2020-038936Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trialDagmar F Hernandez-Suarez0Kyle Melin1Frances Marin-Maldonado2Hector J Nunez3Ariel F Gonzalez4Lorena Gonzalez-Sepulveda5Sona Rivas-Tumanyan6Hetanshi Naik7Gualberto Ruaño8Stuart A Scott9Jorge Duconge10Division of Cardiovascular Medicine, University of Puerto Rico School of Medicine, Medical Sciences Campus, San Juan, Puerto Rico, USADepartment of Pharmacy Practice, School of Pharmacy, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico, USARCMI Program, Academic Affairs Deanship, University of Puerto Rico, Medical Sciences Campus, San Juan, Puerto Rico, USADivision of Cardiovascular Medicine, University of Puerto Rico School of Medicine, Medical Sciences Campus, San Juan, Puerto Rico, USADivision of Cardiovascular Medicine, University of Puerto Rico School of Medicine, Medical Sciences Campus, San Juan, Puerto Rico, USABiostatistics, Epidemiology, and Research Design Core, Hispanic Alliance for Clinical and Translational Research, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico, USAResearch Design and Biostatistics Core, Puerto Rico Clinical and Translational Research Consortium (PRCTRC), Medical Sciences Campus, San Juan, Puerto Rico, USADepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York City, New York, USAHartford Hospital Institute of Living, Hartford, Connecticut, USADepartment of Pathology, Stanford University, Stanford, California, USADepartment of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico Medical Sciences Campus, San Juan, Puerto Rico, USAIntroduction Minority populations in the USA are disproportionately affected by cardiovascular conditions. Reduced responsiveness to clopidogrel among carriers of CYP2C19 variants has been reported in patients with either coronary artery disease (CAD) or acute coronary syndrome (ACS) after the percutaneous coronary intervention (PCI). Previous studies have evaluated CYP2C19 genotyping-guided antiplatelet therapy in selected populations; however, this has yet to be tested among Hispanics. Given the paucity of clinical research on CYP2C19 and antiplatelet clinical outcomes in Hispanics, our study will test the safety and efficacy of a genetic-driven treatment algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics.Methods and analysis This is a multicentre, prospective, non-randomised clinical trial that proposes an assessment of pharmacogenomic-guided DAPT in post-PCI Caribbean Hispanic patients with ACS or CAD. We will recruit 250 patients to be compared with a matched non-concurrent cohort of 250 clopidogrel-treated patients (standard-of-care). Major adverse cardiovascular events (MACEs) such as all-cause death, myocardial infarction (MI), stroke, coronary revascularisation, stent thrombosis and bleedings over 6 months will be the study endpoints. Among the recruited, high-risk patients will be escalated to ticagrelor and low-risk patients will remain on clopidogrel. The primary objective is to determine whether genetic-guided therapy is superior to standard of care. The secondary objective will determine if clopidogrel treatment in low-risk patients is not associated with a higher rate of MACEs compared with escalated antiplatelet therapy in high-risk patients. Patients will be enrolled up to the group’s completion.Ethics and dissemination Approval was obtained from the Institutional Review Board of the University of Puerto Rico Medical Sciences Campus (protocol # A4070417). The study will be carried out in compliance with the Declaration of Helsinki and International Conference on Harmonization Good Clinical Practice Guidelines. Findings will be published in a peer-reviewed journal and controlled access to experimental data will be available.Trial registration number NCT03419325; Pre-results.https://bmjopen.bmj.com/content/10/8/e038936.full
spellingShingle Dagmar F Hernandez-Suarez
Kyle Melin
Frances Marin-Maldonado
Hector J Nunez
Ariel F Gonzalez
Lorena Gonzalez-Sepulveda
Sona Rivas-Tumanyan
Hetanshi Naik
Gualberto Ruaño
Stuart A Scott
Jorge Duconge
Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial
BMJ Open
title Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial
title_full Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial
title_fullStr Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial
title_full_unstemmed Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial
title_short Implementing a pharmacogenetic-driven algorithm to guide dual antiplatelet therapy (DAPT) in Caribbean Hispanics: protocol for a non-randomised clinical trial
title_sort implementing a pharmacogenetic driven algorithm to guide dual antiplatelet therapy dapt in caribbean hispanics protocol for a non randomised clinical trial
url https://bmjopen.bmj.com/content/10/8/e038936.full
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