Validation of a novel direct method to determine reduced adherence to atorvastatin therapy.

IF 5.3 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Jonas Pivoriunas, Nils Tore Vethe, Einar Husebye, Morten W Fagerland, Stein Bergan, Oscar Kristiansen, John Munkhaugen, Elise Sverre
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引用次数: 0

Abstract

Aims: Objective methods to determine statin adherence are requested to improve lipid management. We have recently established a method to detect reduced adherence to atorvastatin therapy with cut-off values based on the sum of atorvastatin and its major metabolites in the blood. We aimed to validate this method in patients with and without cardiovascular disease, and optimize previous cut-off values.

Methods and results: The pharmacokinetic study included 60 participants treated with atorvastatin 20 mg (N = 20), 40 mg (N = 20), and 80 mg (N = 20). Atorvastatin was then stopped and blood samples collected from day zero to day four. Quantification of the parent drug and its metabolites in blood plasma was performed with a liquid chromatography-tandem mass spectrometry assay. The cut-off values for reduced adherence were validated and optimized by calculating diagnostic sensitivity and specificity. Our candidate cut-off value of dose-normalized six-component sum of atorvastatin plus metabolites <0.10 nM/mg provided a sensitivity of 97% and a specificity of 93% for detecting ≥2 omitted doses. An optimized cut-off <0.062 nM/mg provided a sensitivity of 90% and a specificity of 100%. An alternative simplified two-component metabolite sum with a cut-off value <0.05 nM/mg provided a sensitivity of 98% and a specificity of 76%. An optimized cut-off <0.02 nM/mg provided a sensitivity of 97% and a specificity of 98%.

Conclusion: This validation study confirms that our direct method discriminates reduced adherence from adherence to atorvastatin therapy with high diagnostic accuracy. The method may improve lipid management in clinical practice and serve as a useful tool in future studies.

验证确定阿托伐他汀治疗依从性下降的新型直接方法。
目的:为改善血脂管理,需要客观的方法来确定他汀类药物的依从性。我们最近建立了一种检测阿托伐他汀治疗依从性下降的方法,其临界值基于血液中阿托伐他汀及其主要代谢物的总和。我们的目的是在患有和未患有心血管疾病的患者中验证这种方法,并优化以前的临界值:药代动力学研究包括 60 名接受阿托伐他汀 20 毫克(20 人)、40 毫克(20 人)和 80 毫克(20 人)治疗的患者。然后停用阿托伐他汀,并收集第零天至第四天的血样。采用液相色谱-串联质谱法对血浆中的母药及其代谢物进行定量。通过计算诊断灵敏度和特异性,验证并优化了减少依从性的临界值。我们的候选临界值为阿托伐他汀加代谢物的剂量归一化六组分总和 结论:我们的方法是最有效的:这项验证研究证实,我们的直接方法能以较高的诊断准确性区分阿托伐他汀治疗的依从性降低与依从性降低。该方法可改善临床实践中的血脂管理,并可作为未来研究的有用工具。
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来源期刊
European Heart Journal - Cardiovascular Pharmacotherapy
European Heart Journal - Cardiovascular Pharmacotherapy Medicine-Cardiology and Cardiovascular Medicine
CiteScore
10.10
自引率
14.10%
发文量
65
期刊介绍: The European Heart Journal - Cardiovascular Pharmacotherapy (EHJ-CVP) is an international, peer-reviewed journal published in English, specifically dedicated to clinical cardiovascular pharmacology. EHJ-CVP publishes original articles focusing on clinical research involving both new and established drugs and methods, along with meta-analyses and topical reviews. The journal's primary aim is to enhance the pharmacological treatment of patients with cardiovascular disease by interpreting and integrating new scientific developments in this field. While the emphasis is on clinical topics, EHJ-CVP also considers basic research articles from fields such as physiology and molecular biology that contribute to the understanding of cardiovascular drug therapy. These may include articles related to new drug development and evaluation, the physiological and pharmacological basis of drug action, metabolism, drug interactions, and side effects.
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