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Observational Study
. 2025 May 2;11(3):230-240.
doi: 10.1093/ehjcvp/pvae087.

Cost-effectiveness of implementing a genotype-guided de-escalation strategy in patients with acute coronary syndrome

Wout Willem Antoon van den Broek  1 , Jaouad Azzahhafi  1 , Dean R P P Chan Pin Yin  1 , Niels M R van der Sangen  2 , Shabiga Sivanesan  2 , Lea M Dijksman  3 , Ronald J Walhout  4 , Melvyn Tjon Joe Gin  5 , Nicoline J Breet  6 , Jorina Langerveld  7 , Georgios J Vlachojannis  8 , Rutger J van Bommel  9 , Yolande Appelman  10 , Ron H N van Schaik  11 , José P S Henriques  2 , Wouter J Kikkert  2   9 , Jurriën M Ten Berg  1   12
Affiliations
Observational Study

Cost-effectiveness of implementing a genotype-guided de-escalation strategy in patients with acute coronary syndrome

Wout Willem Antoon van den Broek et al. Eur Heart J Cardiovasc Pharmacother. .

Abstract

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.

Keywords: ACS; Coronary artery disease; Cost-effectiveness; Genotype-guided; P2Y12-inhibitor.

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Figures

Figure 1
Figure 1
Cost-effectiveness model. (A) One-year decision tree. ACS; acute coronary syndrome. (B) Long-term Markov model. Markov model transitions in figure: (1) risk of non-fatal stroke based on literature. (2) Risk of non-fatal MI based on literature. (3) Mortality risk for patients with no event based on Dutch population data. (4) Mortality risk after a non-fatal stroke. (5) Mortality risk after a non-fatal MI. (6) Mortality risk at second and subsequent years after a non-fatal stroke. (7) Mortality risk at second and subsequent years after a non-fatal MI. MI; myocardial infarction. The dotted lines indicate the transition of patients in the non-fatal MI or post-MI state to the non-fatal stroke state.
Figure 2
Figure 2
Deterministic sensitivity analysis. Tornado plot showing the net monetary benefit (NMB). In the deterministic sensitivity analysis (DSA), the minimum and maximum value of the parameter range of every individual parameter is alternately put into the model. The results of the DSA depict the influence on the NMB when the minimum or maximum value of the individual parameter is used, while all other parameters stay the same. The base case value of the NBM was 1850.7 DT: decision tree, MI, myocardial infarction.
Figure 3
Figure 3
Probabilistic sensitivity analysis. Cost-effectiveness plane showing the results of the probabilistic sensitivity analysis (PSA) demonstrating the varying outcomes of the Monte Carlo analysis, with 10 000 iterations per patient, where all model inputs are randomly adjusted based on their respective uncertainty distributions. Both the average PSA value and the outcome of the base-case scenario are displayed in the figure. QALY, quality-adjusted life year.
Figure 4
Figure 4
Impact of reducing ticagrelor prices on costs in different scenarios. Results of a scenario analysis demonstrating the impact of reducing ticagrelor prices on total costs in the genotype-guided and standard care cohorts. (A) Total costs based on the base-case analysis and a lifetime horizon. (B) Total costs based on the base-case analysis and a 1-year horizon. (C) Costs based on the scenario with equal distribution over health states and a 1-year horizon.
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