PWIII-005 - EVALUATING THE IMPACT OF PROTON PUMP INHIBITOR USE ON CARDIOVASCULAR OUTCOMES IN PATIENTS RECEIVING CYP2C19 GENOTYPE GUIDED ANTIPLATELET THERAPY IN A REAL-WORLD SETTING.

T. Le, A. Nguyen, M. Winget, N. Kulick, S. Venkatesh, J. Rossi, G. Stouffer, C. Lee; University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Background: Proton pump inhibitors (PPIs) inhibit CYP2C19 and impair the antiplatelet effects of clopidogrel (clop). However, the impact of PPI use on the clinical benefit of CYP2C19 genotype guided antiplatelet therapy (APT) after percutaneous coronary intervention (PCI) is unclear.

Methods: A single center retrospective study included 1895 PCI patients who underwent CYP2C19 genotyping from 2012-19. Prasugrel or ticagrelor (pras/ticag) was recommended in intermediate or poor metabolizers (IM/PMs). Major atherothrombotic events (MAE: death, acute coronary syndrome, stent thrombosis, or ischemic stroke) over 1 year after PCI were compared across CYP2C19-APT groups by multivariable Cox regression in the overall cohort and after stratifying by PPI use.

Results: The study included 605 (32%) PPI treated patients; 461 received omeprazole or esomeprazole. In the overall cohort, MAE rate was higher in CYP2C19 IM/PMs treated with clop compared to those treated with pras/ticag (27 vs 12 events/100 pt-yrs; adj HR 1.7, 95% CI 1.04 – 2.6, p=0.03). Similar results were observed in patients treated with a PPI (28 vs 14 events/100 pt-yrs; adj HR 1.7, 95% CI 0.8 – 3.6, p=0.16) and in those not treated with a PPI (26 vs 12 events/100 pt-yrs; adj HR 1.7, 95% CI 0.96 – 3.1, p=0.07). Clop-treated patients without a CYP2C19 no function allele exhibited no significant difference in MAE compared to pras/ticag in the overall cohort (15 vs 12 events/100 pt-yrs; adj HR 1.0, 95% CI 0.7 – 1.4, p=0.81), the PPI group (18 vs 14 events/100 pt-yrs; adj HR 1.0, 95% CI 0.6 – 1.9, p=0.89), or the non-PPI group (13 vs 12 events/100 pt-yrs; adj HR 0.9, 95% CI 0.6 – 1.4, p=0.65).

Conclusion: These data suggest that PPI use does not modify the clinical outcomes benefit associated with CYP2C19 genotype guided APT after PCI in a real world setting. Evaluation in a larger multicenter study is needed.