Mauro Trincado Ave, María Brión, Alejandro Blanco-Verea, Almudena Gil, Carlos Tilves, Ana Seoane Blanco, María Moure González, Federico García-Rodeja, Pablo de la Fuente, José Ramón González-Juanatey, Moisés Rodríguez Mañero
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引用次数: 0
Abstract
A 25% flecainide dose reduction has been recommended for intermediate metabolizers (IMs); however, studies have yielded contradictory results, likely because of the lack of standardization in CYP2D6 pharmacogenetic classifications. We aimed to address this gap. This cohort study included atrial fibrillation patients prescribed flecainide between 2017 and 2021. CYP2D6 was analyzed, and patient phenotypes were classified using the current standard. For the primary outcome-6-month toxicity or recurrence-normal metabolizers (NMs) were compared with IMs. As a secondary objective, outcomes in poor metabolizers (PMs) and 12-month results were evaluated. A total of 104 patients were enrolled. Overall, 50% were NMs, 36.5% IMs, 6.7% PMs, and 6.7% others. There were no differences between IMs and NMs in the incidence of the primary outcome (29.0% vs. 28.9%, P = 0.99). No significant differences were observed in multivariate analysis ( P = 0.97) or 12-month follow-up ( P = 0.57). PMs had a lower event rate at 6 months ( P = 0.1), which became significant when the follow-up was extended to 1 year (univariate P = 0.04; multivariate P = 0.03). Using a standardized CYP2D6 classification, IMs and NMs showed similar rates of toxicity and recurrence when treated with 100 mg flecainide every 12 hours. Although the small sample size limits definitive conclusions, our findings challenge current recommendations to adjust dosing between NMs and IMs. By contrast, better outcomes were observed in PMs. This raises the question of whether, in an effort to minimize flecainide toxicity, dosing has inadvertently been standardized to subtherapeutic levels for all groups except PMs.
期刊介绍:
Journal of Cardiovascular Pharmacology is a peer reviewed, multidisciplinary journal that publishes original articles and pertinent review articles on basic and clinical aspects of cardiovascular pharmacology. The Journal encourages submission in all aspects of cardiovascular pharmacology/medicine including, but not limited to: stroke, kidney disease, lipid disorders, diabetes, systemic and pulmonary hypertension, cancer angiogenesis, neural and hormonal control of the circulation, sepsis, neurodegenerative diseases with a vascular component, cardiac and vascular remodeling, heart failure, angina, anticoagulants/antiplatelet agents, drugs/agents that affect vascular smooth muscle, and arrhythmias.
Appropriate subjects include new drug development and evaluation, physiological and pharmacological bases of drug action, metabolism, drug interactions and side effects, application of drugs to gain novel insights into physiology or pathological conditions, clinical results with new and established agents, and novel methods. The focus is on pharmacology in its broadest applications, incorporating not only traditional approaches, but new approaches to the development of pharmacological agents and the prevention and treatment of cardiovascular diseases. Please note that JCVP does not publish work based on biological extracts of mixed and uncertain chemical composition or unknown concentration.