Empiric treatment with aspirin and ticagrelor is the most cost-effective strategy in patients with minor stroke or transient ischemic attack.

BACKGROUND: Patients with minor ischemic stroke or transient ischemic attacks (TIAs) are often treated with dual antiplatelet therapy regimens as part of secondary stroke prevention. Clopidogrel, an antiplatelet used in these regimens, is metabolized into its active form by the CYP2C19 enzyme. Patients with loss of function (LOF) mutations in CYP2C19 are at risk for poorer secondary outcomes when prescribed clopidogrel. AIMS: We aimed to determine the cost-effectiveness of three different treatment antiplatelet regimens in ischemic stroke populations with minor strokes or TIAs and how these treatment regimens are influenced by the LOF prevalence in the population. METHODS: Markov models were developed to look at the cost-effectiveness of empiric treatment with aspirin and clopidogrel versus empiric treatment with aspirin and ticagrelor, versus genotype-guided therapy for either 21 or 30 days. Effect ratios were obtained from the literature, and incidence rates and costs were obtained from the national data published by the Singapore Ministry of Health. The primary endpoints were the incremental cost-effectiveness ratios (ICERs). RESULTS: Empiric treatment with aspirin and ticagrelor was the most cost-effective treatment. Genotype-guided therapy was more cost-effective than empiric aspirin and clopidogrel if the LOF was above 48%. Empiric ticagrelor and aspirin was cost saving when compared to genotype-guided therapy. Results in models of dual antiplatelet therapy for 30 days were similar. CONCLUSION: This study suggests that in patients with minor stroke and TIA planned for dual antiplatelet regimens, empiric ticagrelor and aspirin is the most cost-effective treatment regimen. If ticagrelor is not available, genotype-guided therapy is the most cost-effective treatment regimen if the LOF prevalence in the population is more than 48%.

Cost-effectiveness of CYP2C19-guided P2Y12 inhibitors in Veterans undergoing percutaneous coronary intervention for acute coronary syndromes.

AIMS: CYP2C19-guided P2Y12 inhibitor selection can reduce cardiovascular (CV) events and bleeding in patients with acute coronary syndromes (ACSs) 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 Veterans 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 vs. no testing outcomes in 2800 hypothetical Veterans receiving PY212 inhibitor for 12 months post-ACS/PCI (74% clopidogrel, 5% prasugrel, and 21% ticagrelor use at baseline without testing). CYP2C19 loss-of-function (LOF) carrier prevalence was 28%. Model inputs were from studies (bleeding/ischaemic events, CYP2C19-guided therapy effect, health state utilities, CYP2C19 LOF carrier prevalence) and VHA administrative data (costs of events, drugs, CYP2C19 testing; PCI volumes, and P2Y12 inhibitor prescriptions). The primary outcome was cost (2020 US${\$}$) per quality-adjusted life year (QALY) gained. Base-case scenarios, 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 CV-related deaths, and caused 3 bleeds. CYP2C19 testing (vs. no testing) was dominant in the 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 analyses, de-escalation in conjunction with escalation is required for CYP2C19 testing to be cost-effective and high-value. CONCLUSION: In Veterans post-ACS/PCI, CYP2C19-guided P2Y12 inhibitor selection can improve CV outcomes and lower costs for the VHA within 12 months of implementation.