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A novel direct method to determine adherence to atorvastatin therapy in patients with coronary heart disease
Author(s) -
Kristiansen Oscar,
Vethe Nils T.,
Fagerland Morten W.,
Bergan Stein,
Munkhaugen John,
Husebye Einar
Publication year - 2019
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14122
Subject(s) - atorvastatin , medicine , coronary heart disease , statin , pharmacology , metabolite , gastroenterology
Aims 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. Methods 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. Results 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. Conclusion 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.

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