New Fixed‐Dose Combinations of Fenofibrate/Simvastatin Therapy Significantly Improve the Lipid Profile of High‐Risk Patients with Mixed Dyslipidemia Versus Monotherapies

Abstract

SUMMARYAims: Guidelines propose additional therapy to statin to treat elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDLC) in dyslipidemic patients. We evaluated the effects of new fixed-dose combinations (FDC) of fenofibrate/simvastatin on plasma lipids versus simvastatin or fenofibrate monotherapies. Methods: Subjects with mixed dyslipidemia at high or very high cardiovascular risk on stable statin therapy for at least 3 months were included in a randomized, double-blind, active-control, parallel-group study. Patients were treated with FDC fenofibrate/simvastatin 145/20 mg or 145/40 mg, simvastatin 20 mg or 40 mg, or fenofibrate 145 mg for 12 weeks. Plasma lipids, C-reactive protein, and cystatin C were measured before and after treatments. Differences in % changes were compared between FDC fenofibrate/simvastatin and monotherapies. Results: Significant differences between FDC fenofibrate/simvastatin and simvastatin monotherapies were observed for the % change of TG (LS mean difference [two-sided 95% CI]: À32.2% [À38.6%, À25.8%], P < 0.001) and HDL-C (7.5% [4.7%, 10.2%], P < 0.001). A significant difference between the FDC fenofibrate/simvastatin and fenofibrate was observed for LDLC % changes (À34.7% [À40.8%, À28.5%], P < 0.001). Significant differences between FDC fenofibrate/simvastatin and their respective monotherapies were also observed for Apo B and non-HDLC % changes. The FDC were well tolerated with a similar safety profile compared with monotherapies. Conclusions: FDC fenofibrate/simvastatin are effective and well-tolerated therapies to improve the TG and HDLC profile in high-risk patients with mixed dyslipidemia.

Fenofibrate/simvastatin fixed-dose combination in the treatment of mixed dyslipidemia: safety, efficacy, and place in therapy

“… 70 Outstanding results can be obtained with a new fixed-dose combination with fenofibrate 145 mg in a new nanotechnology formulation compared to single medications. 71 As observable from all the studies referred, the higher the baseline dyslipidemia level, the better the effect of combined drugs is.…”

The Effect of Fibrates on Kidney Function and Chronic Kidney Disease Progression: A Systematic Review and Meta-Analysis of Randomised Studies

“…A total of 20,176 patients were included in the eligible studies, 10,249 in the intervention arm and 9841 in the comparator arm while 86 patients received both interventions in the setting of crossover studies. The majority of the studies (n = 21) had examined fenofibrate alone or in combination [7,8,14,15,17,18,[20][21][22][24][25][26][27][28][29][30][31][33][34][35]40,41] and 11 of them fenofibrate vs. placebo [8,14,15,17,18,26,27,31,34,35]. Among the included studies more than half of the participants came from the FIELD and the ACCORD studies.…”

Comparative efficacy and safety of statin and fibrate monotherapy: A systematic review and meta-analysis of head-to-head randomized controlled trials

“…The characteristics of the included studies are available in Table 1. Nineteen studies (reported in 24 articles) met the inclusion criteria [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42], and allocated a total of 7619 participants to either statin or fibrate monotherapy, totaling approximately 4745 person-years of follow-up. Five studies [31,33,[36][37][38] had a follow-up duration of 24 weeks or longer, and the longest follow-up was two years [38].…”

“…Because of the small number of events and different outcome descriptions, we could not pool studies for the outcome of kidney injury. Three studies reported kidney injury related outcomes as renal failure [30,43], renal impairment [27], or renal dysfunction [36]. A total of four cases of kidney injury were reported in the fibrate group and zero in the statin group.…”

“…Two studies https://doi.org/10.1371/journal.pone.0246480.g011 [39,42] reported the outcome of increased fasting blood glucose, with one case occurring in a participant assigned to fibrate [39] and the other in a participant assigned to statin therapy [42]. In a third study, one case each of diabetes mellitus, decompensated type 2 diabetes mellitus, and inadequate control of diabetes mellitus were reported (two participants in the statin group and one participant in the fibrate group) [27]. A single case of deep vein thrombosis was reported in the fibrate group [28,44].…”