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

Kim, Ki-Bum; Touchette, Daniel R.; Cavallari, Larisa H.; Ardati, Amer; DiDomenico, Robert J.

doi:10.1007/s10557-019-06896-8

Cited by 15 publications

(27 citation statements)

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“…[21][22][23][24][25] Genotype-guided therapy with ticagrelor was compared to universal clopidogrel or ticagrelor in four articles. [26][27][28][29] Four articles evaluated the genotype-guided use of the P2Y12 inhibitors ticagrelor or prasugrel as compared against the universal use of P2Y12 inhibitors, that is, clopidogrel, ticagrelor, or prasugrel. [30][31][32][33] In general, key clinical effectiveness data in the majority of the studied comparative models were derived from the 2 landmark clinical trials of antiplatelet therapy in patients with ACS; the TRITION-TIMI 38 clinical trial (prasugrel vs clopidogrel) and the PLATO clinical trial (ticagrelor vs clopidogrel).…”

Section: Characteristics Of the Included Articlesmentioning

confidence: 99%

“…All the studies considered the use of an alternative to clopidogrel in the genotype-guided arm whenever there was LOF allele, regardless of whether it was homozygote (two copies of the LOF allele) or heterozygote (one copy of the LOF allele). Among the 13 included studies, seven were conducted in the United States, 21,22,[24][25][26][27]33 four in China, [29][30][31][32] one in Australia, 28 and one in New Zeeland. 23 Characteristics of the included studies are summarized in Table 1.…”

Section: Characteristics Of the Included Articlesmentioning

confidence: 99%

“…A cost-utility analysis was performed in 11 of 13 studies, and the outcome measure used in these studies was cost/quality-adjusted life-year (QALY). [22][23][24][26][27][28][29][30][31][32][33] The other two studies conducted a cost-effectiveness analysis, and the outcome measure was cost/avoided CV or bleeding event. 21,25 All studies evaluated the generic clopidogrel and branded ticagrelor or prasugrel at the base-case of their analyses.…”

Section: Characteristics Of the Included Articlesmentioning

confidence: 99%

“…Only four articles reported the genotyping methods, in which Wang et al and Crespin et al utilized conventional genotyping, 26,29 whereas Kazi et al and Kim et al utilized point-of-care genotyping. 27,33 Genotype-Guided Therapy With Prasugrel Versus Universal Use of Prasugrel or Clopidogrel Clinical and cost outcomes. In the genotype-guided arm, patients with LOF alleles received prasugrel, while patients without LOF alleles received clopidogrel.…”

Section: Characteristics Of the Included Articlesmentioning

confidence: 99%

“…[26][27][28][29] Sorich et al examined MACE; Wang et al examined MACE as well as stent thrombosis and fatal bleeding; Crespin et al evaluated MI, bleeding, dyspnea, and death; and Kim et al examined MI, ischemic stroke, intracranial hemorrhage, major bleeding, and death. [26][27][28][29] Three articles used similar sources of clinical effectiveness events including the PLATO trial and sub-studies, [26][27][28] whereas Crespin et al and Kim et al used the Medicare program and a meta-analysis by Mega et al, 4 respectively, in addition to the PLATO trial. 26,27 On the other hand, Wang et al relied on local observational studies done in Asian populations.…”

Section: Genotype-guided Therapy With Ticagrelor Versus Universal Usementioning

confidence: 99%

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Economic Evaluations of CYP2C19 Genotype-Guided Antiplatelet Therapy Compared to the Universal Use of Antiplatelets in Patients With Acute Coronary Syndrome: A Systematic Review

AlMukdad

Elewa

Al‐Badriyeh

2020

J Cardiovasc Pharmacol Ther

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Background and Objectives: Clopidogrel is widely used after the percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and requires activation by cytochrome P450 (CYP), primarily CYP2C19. Patients with CYP2C19 loss-of-function alleles are at increased risk of major adverse cardiovascular events, while more expensive novel antiplatelet agents (ticagrelor and prasugrel) are unaffected by the CYP2C19 mutations. This systematic review aims to answer the question about whether overall evidence supports the genotype-guided selection of antiplatelet therapy as a cost-effective strategy in post-PCI ACS. Methods: A systematic literature search of PubMed, EMBASE, EconLit, and PharmGKB was done to identify all 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: The search identified 13 articles, where genotype-guided treatment was compared to universal clopidogrel, ticagrelor, and/or prasugrel. Six studies showed that genotype-guided therapy was cost-effective compared to universal clopidogrel, while 5 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 5, 1, and 3 studies, respectively. Only 2 studies reported that universal ticagrelor was cost-effective compared to genotype-guided treatment. All the included articles had good quality. Conclusion: 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 undergoing PCI.

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Section: Characteristics Of the Included Articlesmentioning

confidence: 99%

Section: Characteristics Of the Included Articlesmentioning

confidence: 99%

Section: Characteristics Of the Included Articlesmentioning

confidence: 99%

Section: Characteristics Of the Included Articlesmentioning

confidence: 99%

Section: Genotype-guided Therapy With Ticagrelor Versus Universal Usementioning

confidence: 99%

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Economic Evaluations of CYP2C19 Genotype-Guided Antiplatelet Therapy Compared to the Universal Use of Antiplatelets in Patients With Acute Coronary Syndrome: A Systematic Review

AlMukdad

Elewa

Al‐Badriyeh

2020

J Cardiovasc Pharmacol Ther

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Cost Effectiveness of Pharmacogenetic Testing for Drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines: A Systematic Review

Morris

Alsaidi

Verbyla

et al. 2022

Clin Pharma and Therapeutics

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The objective of this study was to evaluate the evidence on cost‐effectiveness of pharmacogenetic (PGx)–guided treatment for drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. A systematic review was conducted using multiple biomedical literature databases from inception to June 2021. Full articles comparing PGx‐guided with nonguided treatment were included for data extraction. Quality of Health Economic Studies (QHES) was used to assess robustness of each study (0–100). Data are reported using descriptive statistics. Of 108 studies evaluating 39 drugs, 77 (71%) showed PGx testing was cost‐effective (CE) (N = 48) or cost‐saving (CS) (N = 29); 21 (20%) were not CE; 10 (9%) were uncertain. Clopidogrel had the most articles (N = 23), of which 22 demonstrated CE or CS, followed by warfarin (N = 16), of which 7 demonstrated CE or CS. Of 26 studies evaluating human leukocyte antigen (HLA) testing for abacavir (N = 8), allopurinol (N = 10), or carbamazepine/phenytoin (N = 8), 15 demonstrated CE or CS. Nine of 11 antidepressant articles demonstrated CE or CS. The median QHES score reflected high‐quality studies (91; range 48–100). Most studies evaluating cost‐effectiveness favored PGx testing. Limited data exist on cost‐effectiveness of preemptive and multigene testing across disease states.

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Pharmacogenetics of P2Y₁₂ receptor inhibitors

et al. 2023

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Oral P2Y12 inhibitors are commonly prescribed for cardiovascular disease and include clopidogrel, prasugrel, and ticagrelor. Each of these drugs has its strengths and weaknesses. Prasugrel and ticagrelor are more potent inhibitors of platelet aggregation and were shown to be superior to clopidogrel in preventing major adverse cardiovascular events after an acute coronary syndrome and percutaneous coronary intervention (PCI) in the absence of genotyping. However, both are associated with an increased risk for non‐coronary artery bypass‐related bleeding. Clopidogrel is a prodrug requiring bioactivation, primarily via the CYP2C19 enzyme. Approximately 30% of individuals have a CYP2C19 no function allele and decreased or no CYP2C19 enzyme activity. Clopidogrel‐treated carriers of a CYP2C19 no function allele have decreased exposure to the clopidogrel active metabolite and lesser inhibition of platelet aggregation, which likely contributed to reduced clopidogrel efficacy in clinical trials. The pharmacogenetic data for clopidogrel are most robust in the setting of PCI, but evidence is accumulating for other indications. Guidance is available from expert consensus groups and regulatory agencies to assist with integrating genetic information into P2Y12 inhibitor prescribing decisions, and CYP2C19 genotype‐guided antiplatelet therapy after PCI is one of the most common examples of clinical pharmacogenetic implementation. Herein, we review the evidence for pharmacogenetic associations with clopidogrel response and outcomes with genotype‐guided P2Y12 inhibitor selection and describe guidance to assist with pharmacogenetic implementation. We also describe processes for applying genotype data for P2Y12 inhibitor therapy selection and remaining gaps in the field. Ultimately, consideration of both clinical and genetic factors may guide selection of P2Y12 inhibitor therapy that optimally balances the atherothrombotic and bleeding risks.

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

Cited by 15 publications

References 50 publications

Economic Evaluations of CYP2C19 Genotype-Guided Antiplatelet Therapy Compared to the Universal Use of Antiplatelets in Patients With Acute Coronary Syndrome: A Systematic Review

Economic Evaluations of CYP2C19 Genotype-Guided Antiplatelet Therapy Compared to the Universal Use of Antiplatelets in Patients With Acute Coronary Syndrome: A Systematic Review

Cost Effectiveness of Pharmacogenetic Testing for Drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines: A Systematic Review

Pharmacogenetics of P2Y₁₂ receptor inhibitors

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

Cited by 15 publications

References 50 publications

Economic Evaluations of CYP2C19 Genotype-Guided Antiplatelet Therapy Compared to the Universal Use of Antiplatelets in Patients With Acute Coronary Syndrome: A Systematic Review

Economic Evaluations of CYP2C19 Genotype-Guided Antiplatelet Therapy Compared to the Universal Use of Antiplatelets in Patients With Acute Coronary Syndrome: A Systematic Review

Cost Effectiveness of Pharmacogenetic Testing for Drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines: A Systematic Review

Pharmacogenetics of P2Y12 receptor inhibitors

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Pharmacogenetics of P2Y₁₂ receptor inhibitors