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

Abstract

Minority populations in the USA are disproportionately affected by cardiovascular conditions. Reduced responsiveness to clopidogrel among carriers of <i>CYP2C19</i> 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 <i>CYP2C19</i> genotyping-guided antiplatelet therapy in selected populations; however, this has yet to be tested among Hispanics. Given the paucity of clinical research on <i>CYP2C19</i> 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. 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. 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. NCT03419325; Pre-results.