Cost-Effectiveness of Strategies to Personalize the Selection of P2Y12 Inhibitors in Patients with Acute Coronary Syndrome

Cardiovasc Drugs Ther. 2019 Oct;33(5):533-546. doi: 10.1007/s10557-019-06896-8.

Abstract

Purpose: Perform a cost-effectiveness analysis comparing strategies for selecting P2Y12 inhibitors in acute coronary syndrome (ACS).

Methods: Six strategies for selection of P2Y12 inhibitors in ACS were compared from the US healthcare system perspective: (1) clopidogrel for all (universal clopidogrel); (2) ticagrelor guided by platelet reactivity assay (PRA; clopidogrel + phenotype); (3) ticagrelor use only in CYP2C19 poor metabolizers (genotype + conservative ticagrelor); (4) ticagrelor use in both CYP2C19 intermediate and poor metabolizers (genotype + liberal ticagrelor); (5) ticagrelor use only in patients with CYP2C19 polymorphisms and clopidogrel nonresponse by PRA (genotype + phenotype); and (6) ticagrelor for all (universal ticagrelor). A decision model was developed to model major adverse cardiovascular events and bleeding during 1 year of treatment with a P2Y12 inhibitor. Model inputs were identified from the literature. Lifetime costs were adjusted to 2017 US dollars; quality-adjusted life-years (QALYs) were projected using a Markov model. The primary endpoint was the incremental cost-effectiveness compared to the next best option along the cost-effectiveness continuum. Sensitivity analyses were performed on all model inputs to assess their influence on the incremental cost-effectiveness.

Results: In the base case analysis, incremental cost-effectiveness ratios (ICER) for the clopidogrel + phenotype, genotype + liberal ticagrelor, and universal ticagrelor strategies were $12,119/QALY, $29,412/QALY, and $142,456/QALY, respectively. Genotype + conservative ticagrelor and genotype + phenotype were not cost-effective due to second-order dominance. Genotype + liberal ticagrelor compared to clopidogrel + phenotype demonstrated the highest acceptance (97%) at a willingness to pay (WTP) threshold of $100,000/QALY.

Conclusion: Cost-effective strategies to personalize P2Y12 inhibition in ACS include clopidogrel +phenotype and genotype + liberal ticagrelor. Universal ticagrelor may be considered cost-effective at a higher WTP threshold ($150,000/QALY). Genotype + liberal ticagrelor exhibited the highest acceptability compared to clopidogrel + phenotype over the widest range of WTP thresholds and may be preferred.

Keywords: Acute coronary syndrome; Clopidogrel; Cost-effectiveness; P2Y12 inhibitors; Personalized medicine; Ticagrelor.

Publication types

  • Comparative Study

MeSH terms

  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / economics*
  • Clinical Decision-Making
  • Cost-Benefit Analysis
  • Cytochrome P-450 CYP2C19 / genetics
  • Cytochrome P-450 CYP2C19 / metabolism
  • Decision Support Techniques
  • Decision Trees
  • Drug Costs*
  • Genotype
  • Humans
  • Markov Chains
  • Models, Economic
  • Patient Selection
  • Pharmacogenomic Testing / economics*
  • Pharmacogenomic Variants
  • Phenotype
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / economics*
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Precision Medicine / economics*
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / economics*
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Quality-Adjusted Life Years
  • Time Factors
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • CYP2C19 protein, human
  • Cytochrome P-450 CYP2C19