Implementing a pharmacogenomic-driven algorithm to guide antiplatelet therapy among Caribbean Hispanics: a non-randomised clinical trial.

OBJECTIVES: To assess whether genotype-guided selection of oral antiplatelet drugs using a clinical decision support (CDS) algorithm reduces the rate of major adverse cardiovascular and cerebrovascular events (MACCEs) among Caribbean Hispanic patients, after 6 months. DESIGN: An open-label, multicentre, non-randomised clinical trial. SETTING: Eight secondary and tertiary care hospitals (public and private) in Puerto Rico. PARTICIPANTS: 300 Caribbean Hispanic patients on clopidogrel, both genders, underwent percutaneous coronary intervention (PCI) for acute coronary syndromes, stable ischaemic heart disease and documented extracardiac vascular diseases. INTERVENTIONS: Patients were separated into standard-of-care (SoC) and genotype-guided (pharmacogenetic (PGx)-CDS) groups (150 each) and stratified by risk scores. Risk scores were calculated based on a previously developed CDS risk prediction algorithm designed to make actionable treatment recommendations for each patient. Individual platelet function, genotypes, clinical and demographic data were included. Ticagrelor was recommended for patients with a high-risk score ≥2 in the PGx-CDS group only, the rest were kept or de-escalated to clopidogrel. The intervention took place within 3-5 days after PCI. Adherence medication score was also measured. PRIMARY AND SECONDARY OUTCOMES: The occurrence rate of MACCEs (primary) and bleeding episodes (secondary). Statistical associations between patient time free of events and predictor variables (ie, treatment groups, risk scores) were tested using Kaplan-Meier survival analyses and Cox proportional-hazards regression models. RESULTS: The genotype-guided group had a clinically lower but not significantly different risk of MACCEs compared with the SoC group (8.7% vs 10.7%, p=0.56; HR=0.56). Among high-risk score patients, genotype-driven guidance of antiplatelet therapy showed superiority over SoC in reducing MACCE incidence 6 months postcoronary stenting (adjusted HR=0.104; p< 0.0001). CONCLUSIONS: The potential benefit of implementing our PGx-CDS algorithm to significantly reduce the incidence rate of MACCEs in post-PCI Caribbean Hispanic patients on clopidogrel was observed exclusively among high-risk patients, with apparently no evident effect in other patient groups. TRIAL REGISTRATION NUMBER: NCT03419325.

Implementing a Pharmacogenomic-driven Algorithm to Guide Antiplatelet Therapy among Caribbean Hispanics: A non-randomized prospective cohort study.

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, 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: 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. Clinical Trial Registration Unique Identifier: NCT03419325.