Metabolic Alterations Associated with Atorvastatin/Fenofibric Acid Combination in Patients with Atherogenic Dyslipidaemia: A Randomized Trial for Comparison with Escalated-Dose Atorvastatin

Abstract

In the current study, the metabolic effects of atorvastatin dose escalation versus atorvastatin/fenofibric acid combination were compared using metabolomics analyses. Men and women with combined hyperlipidaemia were initially prescribed atorvastatin (10 mg, ≥4 weeks). Patients who reached low-density lipoprotein-cholesterol targets, but had triglyceride and high-density lipoprotein-cholesterol levels ≥150 mg/dL and <50 mg/dL, respectively, were randomized to receive atorvastatin 20 mg or atorvastatin 10 mg/fenofibric acid 135 mg for 12 weeks. Metabolite profiling of serum was performed and changes in metabolites after drug treatment in the two groups were compared. Analysis was performed using patients’ samples obtained before and after treatment. Of 89 screened patients, 37 who met the inclusion criteria were randomized, and 34 completed the study. Unlike that in the dose-escalation group, distinct clustering of both lipid and aqueous metabolites was observed in the combination group after treatment. Most lipid metabolites of acylglycerols and many of ceramides decreased, while many of sphingomyelins increased in the combination group. Atorvastatin dose escalation modestly decreased lysophosphatidylcholines; however, the effect of combination therapy was variable. Most aqueous metabolites decreased, while l-carnitine remarkably increased in the combination group. In conclusion, the atorvastatin/fenofibric acid combination induced distinct metabolite clustering. Our results provide comprehensive information regarding metabolic changes beyond conventional lipid profiles for this combination therapy.

Plasma Metabolomics Analysis Identifies Abnormal Energy, Lipid, and Amino Acid Metabolism in Abdominal Aortic Aneurysms

“…In addition, the results of our study demonstrated that levels of LysoPC (16: 0/0: 0) and LysoPC (18: 2(9Z,12Z)/0: 0) decreased with the development of AAAs. LysoPC (16: 0) has been confirmed to be related to the inflammation and vulnerability of atherosclerotic plaque, which could affect the progression of AAAs [ 26 , 27 ].…”

Pharmacometabolomics for the Study of Lipid-Lowering Therapies: Opportunities and Challenges

“…More recently, Han et al evaluated in human subjects with combined hyperlipidemia the effects of atorvastatin escalation with atorvastatin/fenofibrate combination [ 117 ]. Serum metabolite profiling revealed distinct metabolite clustering with the combined therapy with respect to statin escalation, including the reduction of acylglycerols and many ceramides, and the increase in serum levels of sphingomyelins and L-carnitine.…”

“…Serum metabolite profiling revealed distinct metabolite clustering with the combined therapy with respect to statin escalation, including the reduction of acylglycerols and many ceramides, and the increase in serum levels of sphingomyelins and L-carnitine. On the other hand, only atorvastatin escalation decreased lysophosphatidylcholines [ 117 ].…”

Atorvastatin Inhibits High-Fat Diet-Induced Lipid Metabolism Disorders in Rats by Inhibiting Bacteroides Reduction and Improving Metabolism

“… 9 Thus, the mechanism of action of atorvastatin was studied by changes in the intestinal microbiome 14 or by analyzing plasma metabolites. 25 …”

“…9 Thus, the mechanism of action of atorvastatin was studied by changes in the intestinal microbiome 14 or by analyzing plasma metabolites. 25 We used an HFD-induced rat model to assess the effect of atorvastatin. We performed the following laboratory investigations: blood biochemistry, liver function tests, and intestinal microbiome analysis through 16S rRNA sequencing.…”