Dong OM, Friede KA, Chanfreau-Coffinier C, Voora D. Cost-effectiveness of CYP2C19-guided P2Y12 inhibitors in Veterans undergoing percutaneous coronary intervention for acute coronary syndromes. Eur Heart J Qual Care Clin Outcomes. 2023 Apr 26;9(3):249-57. doi: 10.1093/ehjqcco/qcac031

AIM: CYP2C19-guided P2Y12 inhibitor selection can reduce cardiovascular events and bleeding in patients with acute coronary syndromes (ACS) post-percutaneous coronary intervention (PCI). The 12-month cost-effectiveness of CYP2C19-guided P2Y12 inhibitor selection for Veterans post-ACS/PCI was evaluated from the Veteran Health Administration's (VHA) perspective.

METHODS AND RESULTS: Using average annualized PCI volumes and P2Y12 inhibitor use from VA data, a decision-analytic model simulated CYP2C19 testing versus no testing outcomes in 2800 hypothetical Veterans receiving PY212 inhibitor for 12 months post-ACS/PCI (74% clopidogrel, 5% prasugrel, 21% ticagrelor use at baseline without testing). CYP2C19 loss-of-function (LOF) carrier prevalence was 28%. Model inputs were from studies (bleeding/ischemic events, CYP2C19-guided therapy effect, health state utilities, CYP2C19 LOF carrier prevalence) and VHA administrative data (costs of events, drugs, CYP2C19 testing; PCI volumes, P2Y12 inhibitor prescriptions). The primary outcome was cost (2020 US${\$}$) per quality-adjusted life year (QALY) gained. Base-case scenario, probabilistic sensitivity analyses, and scenario analyses were completed. CYP2C19-guided therapy resulted in 496 (24%) escalations (clopidogrel to prasugrel/ticagrelor) and 465 (65%) de-escalations (prasugrel/ticagrelor to clopidogrel). CYP2C19 testing averted 1 stroke, 27 myocardial infarctions, 8 cardiovascular-related deaths, and caused 3 bleeds. CYP2C19 testing (vs no testing) was dominant in base-case scenario (0.0027 QALYs gained, ${\$}$527 saved/person) and in 97.1% of simulations, making it cost-effective and high-value. In scenario analysis, de-escalation in conjunction with escalation is required for CYP2C19 testing to be cost-effective and high-value.

CONCLUSIONS: In Veterans post-ACS/PCI, CYP2C19-guided P2Y12 inhibitor selection can improve cardiovascular outcomes and lower costs for the VHA within 12 months of implementation.

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