BACKGROUND: The cost-effectiveness of CYP2C19-guided P2Y12 inhibitor selection for Veterans with acute coronary syndromes (ACS) after percutaneous coronary intervention (PCI) was evaluated from the Veterans Affairs’ (VA) perspective using RCT results from POPular Genetics and TAILOR-PCI.
METHODS: Using average annualized PCI volumes and P2Y12 inhibitor use from 2017-2018 VA Pharmacy data, a decision analytic model simulated 12-month outcomes of CYP2C19 testing versus no testing in a cohort of 2,600 hypothetical Veterans receiving PY212 inhibitor (74% clopidogrel, 5% prasugrel, 21% ticagrelor) for 12 months post-PCI. Adherence to RCT protocols for point-of-care CYP2C19-guided de-escalation and escalation of P2Y12 inhibitors was assumed to be 100%. Additional model inputs were from meta-analysis and RCTs (bleeding/ischemic event rates, CYP2C19 guided therapy effect), VA administrative data (costs of events, drugs, genetic testing), and literature (health state utilities, CYP2C19 variant prevalence). The primary outcome was cost (2019 US$) per quality-adjusted life year (QALY) gained. We completed base-case scenario and probabilistic sensitivity analyses (PSA) using 1,000 Monte Carlo simulations (Oracle Crystal Ball). In scenario analyses, we varied P2Y12 inhibitor therapy use across its observed range in the VA.
RESULTS: CYP2C19 testing was dominant compared to no testing ($243 saving and 0.003 QALY gain per patient) in the base-case scenario. CYP2C19 testing resulted in 580 escalations and 468 de-escalations and compared to no testing, averted 5 strokes, 26 myocardial infarctions, and 7 cardiovascular-related deaths, and caused 20 bleeds. PSA indicated CYP2C19 testing was a dominant strategy in 73% of simulations. In scenario analyses, CYP2C19 testing was cost-effective (<$150,000/QALY gained willingness-to-pay threshold) when ticagrelor use was ≥12% (34/68 VA sites) and dominant when ticagrelor use was ≥16% (29/68 VA sites).
CONCLUSION: CYP2C19-guided P2Y12 inhibitor selection can improve cardiovascular outcomes for Veterans with ACS/PCI and lower costs for the VA in the first year of testing, particularly for sites using ticagrelor at higher rates.
