Genotype-guided prescribing predictors in CYP2C19 intermediate metabolizers receiving percutaneous coronary intervention

Abstract

Background: Previous differences in guideline recommendation strength for CYP2C19 intermediate metabolizers may have limited genotype (PGx)-optimal post-percutaneous coronary intervention antiplatelet prescribing. Results: In this single-center retrospective observational cohort study of CYP2C19 intermediate metabolizers, patients prescribed PGx-optimal therapy were younger and less likely on anticoagulation (2 vs 12%; p = 0.006). More patients prescribed PGx-optimal therapy possessed commercial insurance (36 vs 7%; p < 0.001), which was a predictor for PGx-optimal selection (OR: 6.464; 95% CI: 2.386–17.516; p < 0.001). Conclusion: Anticoagulation use was significantly associated with clopidogrel use (OR: 0.138; 95% CI: 0.026–0.730; p = 0.020). No statistical difference in composite major adverse cardiovascular events (5 vs 14%; p = 0.173) or bleeding (8 vs 6%; Not significant) was observed between PGx-optimal and PGx-suboptimal therapy.

TWEETABLE ABSTRACT

Not all CYP2C19 intermediate metabolizers undergoing PCI are prescribed genotype-optimal P2Y12 antiplatelet therapy. Commercial insurance and no anticoagulant were found to be associated with ticagrelor and prasugrel prescribing in this population.

Summary points

• A weaker strength of recommendation between past and current Clinical Pharmacogenetics Implementation Consortium (CPIC) CYP2C19-clopidogrel guideline prescribing recommendation strengths for CYP2C19 intermediate metabolizers may have influenced the adoption of prescribing prasugrel or ticagrelor for patients found to be CYP2C19 intermediate metabolizers.

• Previous CPIC prescribing recommendations for CYP2C19 intermediate metabolizers being prescribed clopidogrel for coronary indications had a moderate recommendation class, but now are reclassed as strong. It is unclear how other patient socioeconomic factors may influence P2Y12 antiplatelet prescribing and if the impact of a moderate recommendation strength may have impacted post-PCI outcomes.

• A single-center, retrospective observational cohort study was conducted in a population of mainly non-European descent. CYP2C19 intermediate metabolizers were stratified into two groups based on P2Y12 antiplatelet prescribed.

• The primary outcome was a composite of major adverse cardiovascular events (MACE). Secondary outcomes included socioeconomic characteristics.

• No difference in MACE were observed between patients prescribed PGx-optimal and PGx-suboptimal therapy; however, this small sample size likely limited the ability to detect MACE or bleeding outcomes.

• Insurance coverage and concomitant anticoagulation therapy were predictors that impacted P2Y12 inhibitor agent selection.

• Future studies should evaluate the impact of socioeconomic factors to better understand their impact on prescribing in the context of PGx-guided therapies.

• As pharmacogenetic testing continues to expand, evaluating the impact of pharmacogenetic prescribing guideline recommendation should be undertaken to better understand their impact on prescriber acceptance of PGx-based prescribing recommendations.

Keywords: :

• clopidogrel
• CYP2C19
• dual antiplatelet therapy
• pharmacogenetics
• socioeconomic factor

Author contributions

JJ Park: design, data acquisition, analysis/interpretation, drafting/revising/reviewing manuscript. GY Cabel: design, data acquisition, analysis, drafting/revising/reviewing manuscript. KK Cheng: design, data analysis/interpretation, revising/reviewing manuscript. J Dang: design, data acquisition, analysis, drafting/revising/reviewing manuscript. AK Ardati: conception, drafting/reviewing manuscript. J Han: design, data analysis/interpretation, drafting/revising/reviewing manuscript. JC Lee: conception/design, data analysis/interpretation, drafting/revising/reviewing manuscript

Financial disclosure

The authors have no financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

This study protocol (2020 – 0376) was approved by the Institutional Review Board, Office for the Protection of Research Subjects at the University of Illinois Chicago. Due to the nature of the retrospective chart review involving no more than minimal risk, a waiver of participant informed consent was approved.