2026 Southeastern Residency Conference

Title: Pharmacogenomic- and Drug-Drug Interaction-Guided Antiplatelet Therapy in Veterans Taking Clopidogrel and Omeprazole
Authors: Sydney Magrath, Julianne Isaac, David Deen
Background:
Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality, with antiplatelet therapy as the foundation for secondary prevention. Clopidogrel, a widely prescribed P2Y12 inhibitor, exhibits variable efficacy due to CYP2C19 genetic polymorphisms and drug-drug interactions, especially with proton-pump inhibitors (PPIs), such as omeprazole. Consensus statements and leading medical journals have begun to recommend utilizing genotype-guided therapy to optimize outcomes in specific indications, such as acute coronary syndrome (ACS) with or without percutaneous coronary intervention (PCI), to optimize outcomes, yet implementation in clinical practice remains limited. The objective of this project is to reduce category X drug-drug interactions between clopidogrel and omeprazole and assess the feasibility of pharmacogenomic testing in Veterans with ASCVD at high risk for major adverse cardiovascular events (MACE).
Methods:
This prospective, interventional quality improvement project utilized a data query to identify Veterans with ASCVD or post-PCI who were prescribed clopidogrel and omeprazole from September 2022 to December 2025 at the Ralph H Johnson VA Health Care System. Veterans were contacted to discuss pharmacogenomic testing and drug-interaction risks and offered to switch to a non-interacting PPI, de-escalate off PPI or to a histamine-2 receptor antagonist where appropriate. Veteran’s most recent blood pressure, lipid panel, and medication list were reviewed for guideline-recommended interventions. Primary outcome was composite implementation rate, defined as proportion of patients contacted who (1) underwent PPI modification and/or (2) have a final antiplatelet regimen that follows Clinical Pharmacogenetics Implementation Consortium (CPIC) and American College of Cardiology (ACC) recommendations. Secondary outcome was incidence of thrombotic events, bleeding, ticagrelor-associated dyspnea, and worsening dyspepsia following intervention. Tertiary outcome was to assess pharmacist interventions.
Results: 
Of the 82 patients on clopidogrel and omeprazole with an included ICD-10 code or procedure code, 59 met inclusion criteria and 51 were successfully contacted. At visit 1, 50 of 51 patients agreed to PPI modification and 43 completed pharmacogenomic testing. Nine of the 43 were CYP2C19 intermediate metabolizers, suggesting possible indication for antiplatelet therapy change. All but one patient with CAD indicated for clopidogrel change accepted a therapy modification. Ultimately, 50 of 51 patients had final antiplatelet regimens aligned with CPIC and ACC guidance therefore 98% meeting composite implementation rate.
No thrombotic or bleeding events occurred. Among patients switched to ticagrelor, 1 of 2 experienced dyspnea. Five patients reported worsening dyspepsia after PPI modification, of whom 85% were CYP2C19 rapid metabolizers. Pharmacist interventions included 14 medication reconciliations, 48 adherence counseling sessions, 10 lipid-related interventions, and one antihypertensive intervention.
Conclusion:
This project demonstrated high implementation rates and strong patient acceptance in addressing high-risk clopidogrel-omeprazole DDIs. Genotype-guided antiplatelet therapy was feasible in routine practice and did not result in thrombotic or bleeding events during the project period. Reported adverse effects were minimal and consistent with known drug profiles. These findings support the integration of pharmacist-driven pharmacogenomics and medication optimization into cardiovascular risk-reduction efforts within the Veteran population. Future pathways include identifying eligible patients during inpatient ACS/PCI admissions for earlier PPI modification and pharmacogenomic testing, followed by coordinated outpatient follow-up to optimize antiplatelet therapy.