Department of Medicine, Vestre Viken Trust, Drammen Hospital, Drammen, Norway.
Department of Behavioural Sciences in Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Br J Clin Pharmacol. 2019 Dec;85(12):2878-2885. doi: 10.1111/bcp.14122. Epub 2019 Nov 3.
Objective methods to monitor statin adherence are needed. We have established a liquid chromatography-tandem mass spectrometry assay for quantification of atorvastatin and its metabolites in blood. This study aimed to develop an objective drug exposure variable with cut-off values to discriminate among adherence, partial adherence and nonadherence to atorvastatin therapy in patients with coronary heart disease.
Twenty-five patients treated with atorvastatin 10 mg (n = 5), 20 mg (n = 6), 40 mg (n = 7) and 80 mg (n = 7) participated in a directly observed atorvastatin therapy study to confirm baseline adherence. After the directly observed therapy, half of the patients (test group) were instructed to stop taking atorvastatin and return for blood sample collection the subsequent 3 days. Levels of atorvastatin and metabolites were compared between the test group and the adherent control group.
The sum of parent drug and all measured primary metabolites correlated well with the atorvastatin dose administered (Spearman's rho = 0.71, 95% CI 0.44-0.87). The dose-normalized atorvastatin plus metabolites concentrations completely separated the partially adherent test group from the controls at 0.18 nM/mg after 3 days without atorvastatin. To reduce the risk of misinterpreting adherent patients as partially adherent, a corresponding cut-off at 0.10 nM/mg is proposed. A metabolite level of 2-OH atorvastatin acid <0.014 nmol/L provided the optimal cut-off for nonadherence.
A direct method to discriminate among adherence, partial adherence and nonadherence to atorvastatin therapy in patients with coronary heart disease has been developed. This tool may be important for novel studies on adherence and potentially useful in clinical practice.
需要有客观的方法来监测他汀类药物的依从性。我们已经建立了一种液相色谱-串联质谱法来定量检测血液中的阿托伐他汀及其代谢物。本研究旨在开发一种客观的药物暴露变量，并确定其截值，以区分冠心病患者对阿托伐他汀治疗的依从、部分依从和不依从。
25 名接受阿托伐他汀 10mg（n=5）、20mg（n=6）、40mg（n=7）和 80mg（n=7）治疗的患者参加了一项直接观察阿托伐他汀治疗的研究，以确认基线依从性。直接观察治疗后，一半的患者（试验组）被指示停止服用阿托伐他汀，并在随后的 3 天内返回采集血样。比较试验组和依从性对照组的阿托伐他汀和代谢物水平。
母体药物和所有测量的主要代谢物的总和与给予的阿托伐他汀剂量相关性良好（Spearman's rho=0.71，95%置信区间 0.44-0.87）。在 3 天没有阿托伐他汀后，剂量归一化的阿托伐他汀加代谢物浓度完全将部分依从的试验组与对照组分开，截值为 0.18nM/mg。为了降低将依从性患者误诊为部分依从的风险，建议将相应的截值设定为 0.10nM/mg。阿托伐他汀 2-羟基酸的代谢物水平<0.014nmol/L 为不依从提供了最佳的截值。
已经开发出一种直接区分冠心病患者对阿托伐他汀治疗的依从、部分依从和不依从的方法。该工具可能对依从性的新研究很重要，并在临床实践中可能有用。
