CYP2C19 genotype-guided antithrombotic treatment versus conventional clopidogrel therapy in peripheral arterial disease: study design of a randomized controlled trial (GENPAD).

Autor: Kranendonk J; Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Josephine.Kranendonk@radboudumc.nl., Willems LH; Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands., Vijver-Coppen RV; Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands., Coenen M; Department of Human Genetics, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands., Adang E; Department of Epidemiology and Biostatistics, Radboud University Medical Center, Nijmegen, The Netherlands., Donders R; Department for Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands., Zeebregts CJ; Department of Surgery, Division of Vascular Surgery, University Medical Center Groningen, University Of Groningen, Groningen, The Netherlands., Deneer V; Department of Clinical Pharmacy, Division of Laboratories, Pharmacy and Biomedical Genetics University Medical Center Utrecht, Utrecht, The Netherlands; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht university, Utrecht, The Netherlands., Reijnen M; Department of Surgery, Rijnstate Hospital, Arnhem, The Netherlands; Multimodality Medical Imaging Group, Faculty of Science and Technology, University of Twente, Enschede, The Netherlands., Kramers C; Department of Internal Medicine and Pharmacology-Toxicology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Clinical Pharmacy, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands., Warlé MC; Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands.
Jazyk: angličtina
Zdroj: American heart journal [Am Heart J] 2022 Dec; Vol. 254, pp. 141-148. Date of Electronic Publication: 2022 Aug 19.
DOI: 10.1016/j.ahj.2022.08.001
Abstrakt: Background: Clopidogrel is recommended in international guidelines to prevent arterial thrombotic events in patients with peripheral arterial disease (PAD). Clopidogrel itself is inactive and metabolism is dependent on the CYP2C19 enzyme. About 30% of Caucasian PAD patients receiving clopidogrel carry 1 or 2 CYP2C19 loss-of-function allele(s) and do not or to a limited extent convert the prodrug into its active metabolite. As a result, platelet inhibition may be inadequate which could lead to an increased risk of adverse clinical events related to arterial thrombosis. A CYP2C19 genotype-guided antithrombotic treatment might be beneficial for PAD patients.
Methods: GENPAD is a multicenter randomized controlled trial involving 2,276 PAD patients with an indication for clopidogrel monotherapy. Patients with a separate indication for dual antiplatelet therapy or stronger antithrombotic therapy are not eligible for study participation. Patients randomized to the control group will receive clopidogrel 75 mg once daily without pharmacogenetic guidance. Patients randomized to the intervention group will be tested for carriage of CYP2C19 *2 and *3 loss-of-function alleles, followed by a genotype-guided antithrombotic treatment with either clopidogrel 75 mg once daily for normal metabolizers, clopidogrel 150 mg once daily for intermediate metabolizers, or acetylsalicylic acid 80 mg once daily plus rivaroxaban 2.5 mg twice daily for poor metabolizers. The primary outcome is a composite of myocardial infarction, ischemic stroke, cardiovascular death, acute or chronic limb ischemia, peripheral vascular interventions, or death. The secondary outcomes are the individual elements of the primary composite outcome and clinically relevant bleeding complications.
Conclusion: The aim of the GENPAD study is to evaluate the efficacy, safety, and cost-effectiveness of a genotype-guided antithrombotic treatment strategy compared to conventional clopidogrel treatment in PAD patients.
Competing Interests: Declaration of competing interest The authors declare that they have no competing interests.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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