Economic Evaluation of the Cyp2c19 Genotype-Guided Antiplatelet Therapy Compared To Universal Use of Ticagrelor or Clopidogrel in Qatar

Abstract

Background: Clopidogrel requires activation primarily by cytochrome P450 2C19 (CYP2C19). Patients with CYP2C19 loss-of-function alleles (LOF) are at increased risk of major adverse cardiovascular events. Ticagrelor is a more effective and expensive alternative antiplatelet agent that is unaffected by the CYP2C19 polymorphism. The main aim of the current thesis is to evaluate the cost-effectiveness of CYP2C19*2/*3 genotype-guided therapy compared to the universal use of ticagrelor or clopidogrel after a percutaneous coronary intervention (PCI) with acute coronary syndrome (ACS). With the increasing size of relevant economic literature, another aim of the thesis was to perform a systematic review to answer the question about whether the overall evidence supports the genotype-guided selection of antiplatelet therapy as a cost effective strategy in post-PCI ACS. Methods: A two-parts model, including a one-year decision-analytic model and a 20 years follow-up Markov model, was created from the Qatari healthcare provider's perspective, to follow the use of (i) universal clopidogrel, (ii) universal ticagrelor, and (iii) genotype-guided antiplatelet therapy. Outcome measures were the incremental cost-utility ratio (ICUR) and incremental cost-effectiveness ratio (ICER) of genotype guided therapy. Therapy success was defined as survival without myocardial infarction, stroke, stent thrombosis, cardiovascular death, or the no therapy discontinuation because of adverse events, i.e. major bleeding and dyspnea. Via a Monte Carlo simulation, the model was based on multivariate analysis. For the systematic review, a literature search of PubMed, Embase, EconLit, and PharmGKB was done to identify all of the economic evaluations related to genotype guided therapy compared to the universal use of antiplatelets in ACS patients. Quality of Health Economic Studies tool was used for quality assessment. Results: Genotype-guided therapy was between dominant and cost-effective compared to universal clopidogrel in 100%, over the one-year duration (mean ICER of QAR 22,215 per case of success) and the long-term follow up. Genotype-guided therapy was dominant compared to universal ticagrelor in 60% of the cases over the one-year model, and cost-effective in 96% of the cases over the long term (ICUR of QAR 5,036 per QALY). Universal clopidogrel was dominant in 63% of the cases in the clinical outcomes over the one-year model, and cost-effective in 99% of the cases over the long term (ICUR of QAR 38,650 per QALY). One-way and multivariate sensitivity analyses confirmed the robustness of the study results. The literature systematic review identified 13 articles. Six studies showed that genotype-guided therapy was cost-effective compared to universal clopidogrel, while five studies showed that it was dominant. One study specified that genotype-guided with ticagrelor is cost-effective only in both CYP2C19 intermediate and poor metabolizers. Genotype-guided therapy was dominant when compared to universal prasugrel, ticagrelor, or both in five, one, and three studies, respectively. Only two studies reported that universal ticagrelor was cost-effective compared to genotype guided treatment. All of the included articles had good quality. Conclusion: CYP2C19 genotype-guided therapy appears to be the preferred antiplatelet strategy over the universal use of ticagrelor or clopidogrel for post-PCI patients in Qatar. Based on current economic evaluations in the literature, implementing CYP2C19 genotype-guided therapy is a cost-effective approach in guiding the selection of medication in patients with ACS post-PCI.