Background: After percutaneous coronary intervention (PCI), clopidogrel-resistant patients are at an increased risk of major adverse cardiovascular and cerebrovascular events (MACCEs). We aimed to assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the occurrence of these ischemic events and improves outcomes among Caribbean Hispanic patients from Puerto Rico, who are underrepresented in clinical pharmacogenomic (PGx)-guided implementation studies. Methods: Individual platelet function testing (PRU) measures, CYP2C19*2 and PON1 rs662 genotypes, and clinical and demographic data from 8 medical facilities were included. Patients were separated into standard-of-care (SoC) and genotype-guided groups (150 each). Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Alternative therapy with ticagrelor was recommended for patients with a high-risk score ?2. Statistical associations between patient time free of MACCEs and predictor variables (i.e., treatment groups, risk scores) were tested in this population using Kaplan-Meier survival analyses and Cox proportional-hazards regression models. Results: The median age of participants is 67 years; BMI: 27.8; 48% women; 14% smokers; 59% with type-2 diabetes mellitus (T2DM). Among patients with high-risk scores who were free from MACCE events 6 months after coronary stenting, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in terms of reducing the incidence rate of atherothrombotic events. Conclusions: The clinical utility of our PGx-driven CDS algorithm to reduce the incidence rate of MACCEs among post-PCI Caribbean Hispanic patients on clopidogrel was externally demonstrated.

The authors have declared no competing interest.

Clinical Trial Registration Unique Identifier: NCT03419325

This work was supported in part by CCRHD-RCMI grant #2U54 MD007600 from the National Institute on Minority Health and Health Disparities (NIMHD) of the National Institutes of Health (NIH), the Postdoctoral Master in Clinical and Translational Research Program of the Hispanic Clinical and Translational Research Education and Career Development (HCTRECD) award (grant #R25 MD007607, NIMHD, NIH) and by the National Institute of General Medical Sciences (NIGMS)-Research Training Initiative for Student Enhancement (RISE) Program grant R25 GM061838. The Hispanic Alliance for Clinical and Translational Research (Alliance) is supported by the National Institute of General Medical Sciences (NIGMS), NIH, under award #U54 GM133807.

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The study secured Institutional Review Board (IRB) approval (# A4070417) and is therefore in compliance with institutional regulatory requirements. The IRB office at UPR-MSC (IORG000223; Federal-wise Assurance #FWA00005561) is approved by the Office for Human Research Protection (OHRP), Department of Health and Human Services.

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The data that support the findings of this study are available on request from the corresponding author (Dr. Jorge Duconge). The data are not publicly available due to restrictions as they contain information that could compromise the privacy of research participants.