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Cost-effectiveness of implementing a genotype-guided de-escalation strategy in patients with acute coronary syndrome
Wout Willem Antoon van den Broek1, Jaouad Azzahhafi1, Dean R P P Chan Pin Yin1
1Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.
Insights
Genotype-guided P2Y12-inhibitor de-escalation in acute coronary syndrome (ACS) patients is cost-saving and improves quality-adjusted life years (QALYs). This personalized approach reduces bleeding risk without compromising therapeutic effectiveness, offering a valuable strategy for clinical practice.
Area of Science:
- Cardiology
- Pharmacogenomics
- Health Economics
Background:
- Acute coronary syndrome (ACS) patients often receive dual antiplatelet therapy (DAPT) with P2Y12 inhibitors.
- Genetic variations, such as CYP2C19 loss-of-function alleles, influence patient response to P2Y12 inhibitors like clopidogrel, ticagrelor, and prasugrel.
- De-escalation strategies aim to optimize treatment by tailoring therapy based on genetic profiles to balance efficacy and safety.
Purpose of the Study:
- To evaluate the cost-effectiveness of a genotype-guided P2Y12-inhibitor de-escalation strategy compared to standard DAPT in ACS patients in the Netherlands.
- To assess the impact of this personalized approach on healthcare costs and quality-adjusted life years (QALYs) over a lifetime horizon.
Main Methods:
- A 1-year decision tree model was developed using data from the FORCE-ACS registry.
- A lifelong Markov model was employed to compare lifetime costs and QALYs for a cohort of 1000 patients.
- Cost-effectiveness analysis was conducted from the perspective of the Dutch healthcare system.
Main Results:
- The genotype-guided de-escalation strategy resulted in an increase of 57.73 QALYs and a cost saving of €808,788 compared to standard DAPT.
- Probabilistic sensitivity analysis indicated that the genotype-guided strategy was cost-saving in 96% and increased QALYs in 87% of simulations.
- The strategy remained cost-effective and dominant even when P2Y12 inhibitor prices were equalized and across various other sensitivity analyses.
Conclusions:
- A genotype-guided de-escalation strategy for ACS patients is both cost-saving and improves QALYs compared to standard DAPT.
- This personalized pharmacogenomic approach demonstrates significant potential for implementation in routine clinical practice.
- The findings support the integration of genetic testing to guide P2Y12-inhibitor selection in ACS management.
Aims:
A genotype-guided P2Y12-inhibitor de-escalation strategy, switching acute coronary syndrome (ACS) patients without a CYP2C19 loss-of-function allele from ticagrelor or prasugrel to clopidogrel, has shown to reduce bleeding risk without affecting the effectivity of therapy by increasing ischaemic risk. We estimated the cost-effectiveness of this personalized approach compared to standard dual antiplatelet therapy (DAPT; aspirin plus ticagrelor/prasugrel) in the Netherlands.
Methods And Results:
We developed a 1-year decision tree based on results of the FORCE-ACS registry, comparing a cohort of ACS patients who underwent genotyping with a cohort of ACS patients treated with standard DAPT. This was followed by a lifelong Markov model to compare lifetime costs and quality-adjusted life years (QALYs) for a fictional cohort of 1000 patients. The cost-effectiveness analysis was performed from the perspective of the Dutch healthcare system. A genotype-guided de-escalation strategy led to an increase of 57.73 QALYs and saved €808788 compared to standard DAPT based on a lifetime horizon. Probabilistic sensitivity analysis showed that the genotype-guided strategy was cost-saving in 96% and increased QALYs in 87% of simulations. The intervention remained cost-effective in the scenario where prices for all P2Y12 inhibitors were equalized. The genotype-guided strategy remained dominant in various other scenarios and sensitivity analyses.
Conclusion:
A genotype-guided de-escalation strategy in patients with ACS was both cost-saving and yielded higher QALYs compared to standard DAPT, highlighting its potential for implementation in clinical practice. Trial registration: ClinicalTrials.gov identifier: NCT03823547.
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