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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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. 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引用次数: 0
摘要
建议中间代谢物(IMs)减少25%的氟氯胺剂量;然而,研究得出了相互矛盾的结果,可能是由于CYP2D6药物遗传分类缺乏标准化。我们的目标是解决这一差距。该队列研究包括2017-2021年间服用氟氯胺的房颤患者。分析CYP2D6,并使用现行标准对患者表型进行分类。对于主要结果(6个月毒性或复发),将正常代谢物(NMs)与中间代谢物(IMs)进行比较。作为次要目标,评估代谢不良患者(PMs)的结果和12个月的结果。共有104名患者入组。总的来说,50%是NMs, 36.5%是im, 6.7%是pm, 6.7%是其他。在主要结局的发生率上,IMs和NMs之间没有差异(29.0% vs 28.9%, p=0.99)。多因素分析(p=0.97)和12个月随访(p=0.57)无显著差异。PMs在6个月时的事件发生率较低(p=0.1),当随访延长至1年时,这一点变得显著(单变量p=0.04;多元p = 0.03)。使用标准化的CYP2D6分类,每12小时给予100mg氟卡奈时,IMs和NMs的毒性和复发率相似。虽然小样本量限制了明确的结论,但我们的发现挑战了目前在NMs和IMs之间调整剂量的建议。相比之下,pm组观察到更好的结果。这就提出了一个问题:为了尽量减少氟氯胺的毒性,除了经前综合征外,所有组的剂量是否在不经意间被标准化到亚治疗水平?
Relevance of CYP2D6 in the Efficacy and Toxicity of Flecainide in Patients With Atrial Fibrillation: A Cohort Study.
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.