The trough plasma concentration of atorvastatin metabolites has a moderate correlation with a decrease in the levels of low-density lipoprotein cholesterol, according to the results of a randomized double‐blind crossover trial. Atorvastatin metabolites hold potential value in monitoring and optimizing the drug dosage for optimal clinical efficacy.
Statins form the standard treatment in the primary and secondary prevention of coronary heart disease (CHD) based on their role in reducing the levels of low-density lipoprotein cholesterol (LDL-C). Factors that influence the clinical response to statins include baseline LDL-C levels, alcohol intake, smoking, gender, age, ethnicity, and diabetes. Additionally, baseline LDL-C levels are often unknown to treating physicians and are affected by diet and other cholesterol-lowering drugs. Therefore, LDL-C is not considered an optimal biomarker for measuring drug response to statins.
To understand the role of plasma levels of statin metabolites in predicting drug response, an exploratory analysis of a randomized double‐blind crossover trial on the muscle side effects of atorvastatin in coronary patients, dubbed the MUSE trial, assessed the association between plasma levels of atorvastatin metabolites and reduction in LDL-C levels. The study’s findings are published in the journal Pharmacology Research and Perspectives.
Baseline Characteristics
The study comprised intervention and control groups with 70 and 40 participants, respectively. All participants were Caucasian, and the mean age of the study population was 64.0 ± 9.1 years. There were 23 female participants in the intervention group and 12 in the control group.
Atorvastatin and Low-Density Lipoprotein Cholesterol
The mean reduction in the levels of LDL-C in the atorvastatin and control group participants was 2.1 ± 0.7 mmol/L at the end of the treatment period. There were no significant differences in the level of LDL-C reduction according to the order of treatment between control and intervention (p = 0.202).
Atorvastatin Metabolites and Low-Density Lipoprotein Cholesterol
There was a large inter-individual variation in the concentrations of atorvastatin and atorvastatin metabolites 24 hours after the last scheduled dose among the intervention group participants. The relative standard deviation ranged from 77% to 118%. The study findings indicated a correlation between plasma levels of atorvastatin and its metabolites, particularly 4-OH-atorvastatin, and a reduction in the LDL-C levels.
Atorvastatin Metabolites and SLCO1B1 Genotype
The control and intervention group participants with higher concentrations of atorvastatin metabolites were found to have at least one SLCO1B1*5 allele. The mean reduction in LDL-C levels was greater, yet non-significant, in the subset of patients with the SLCO1B1*1/*5 genotype compared to patients with the SLCO1B1*1/*1 genotype.
Source:
Sverre, E., Munkhaugen, J., Kristiansen, O., Weedon‐Fekjær, H., Peersen, K., Gjertsen, E., Gullestad, L., Bergan, S., Husebye, E., & Vethe, N. T. (2023). Plasma concentration of atorvastatin metabolites correlates with low‐density lipoprotein cholesterol reduction in patients with coronary heart disease. Pharmacology Research & Perspectives, 11(3). https://doi.org/10.1002/prp2.1089
