Evaluating Pharmacogenomic Variants for Cardiology Therapeutics (CARES2)

Evaluating Pharmacogenomic Variants for Cardiology Therapeutics: the Lighthouse Pilot (Association Between Genetic Variant Scores and P2Y12 Inhibitor Effects)

Cipherome's Lighthouse is a clinical decision support tool that incorporates a patient's pharmacogenetic information to determine therapeutic strategy, including determining appropriate dosage or assessing the likelihood of toxicity of a therapeutic regimen.

The Lighthouse tool incorporates pharmacogenetic (PGx) variants from well-established, evidence-based guidelines to provide personalized drug response profile(s) to guide treatment decisions. The patient specimen is genotyped using a proprietary, carefully curated pharmacogenetic variant panel to determine the individual's phenotype. The Lighthouse report (PGx findings) are provided to the clinician, and a notification is generated when the patient has a genotype with a deleterious drug-metabolizing phenotype. Evaluating the South Texas community for the pilot project will enhance the understanding of the impact of genetic variants on individuals of Hispanic/Latino ancestry, especially as the variants pertain to the efficacy and safety of medications.

There will be two study arms: Conventional therapy (controls)-treatment with clopidogrel and no pre-emptive genotyping Genotype-guided therapy (experimental)

Treatment with clopidogrel 75 mg daily for non-carriers Treatment with ticagrelor 90 mg twice daily for carriers

The cumulative direct medical cost (admissions, procedures, clinical visits, blood transfusions, drugs) of percutaneous insertion of stents (PCIs) and associated major adverse cardiovascular and cerebrovascular events (MACCE) including non-fatal myocardial infarction, non-fatal stroke, cardiovascular mortality, severe recurrent ischemia and stent thrombosis, and the costs of P2Y12 inhibitors and pharmacogenomic test costs.

Reduced treatment failures within 30, 60, 90 days, and 12 months of receiving clopidogrel in participants with reduced function alleles (CYP2C19 *2 or *3)

Reduced major or minor bleeding events within 30, 60, 90 days, and 12 months of receiving clopidogrel in participants with increased function alleles (CYP2C19 *17)

Assessment of the correlation of clinical factors (age, labs, medications) on predicting and preventing adverse drug reactions

Assess the correlation of clinical factors (age, liver function tests, concomitant medications, etc.) on predicting and preventing adverse drug reactions (ADRs).

Inclusion Criteria: Subjects over 18 years of age, who are: On clopidogrel, prasugrel or ticagrelor after percutaneous stent Completed informed consent Exclusion Criteria: Failure to provide informed consent. Lost to follow-up prior to 60 days.

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