Pemafibrate Tends to have Better Efficacy in Treating Dyslipidemia than Fenofibrate

Author(s): Haizhou Wang, Haiou Li, Yunjiao Zhou, Jing Liu, Fan Wang*, Qiu Zhao*.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 44 , 2019

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Abstract:

Aims: To compare the efficacy of pemafibrate (PF) and fenofibrate (FF) in treating dyslipidemia.

Methods: A comprehensive search was performed on the public database to identify relevant randomized controlled trials (RCTs), which compared the effects of PF and FF treatment in lipid parameters among patients with dyslipidemia. Mean difference (MD) and 95% confidence intervals (CI) were pooled for continuous outcomes, whereas odds ratio (OR) and 95% CI were calculated for dichotomous outcomes.

Results: Three RCTs were included with a total of 744 patients (PF=547 and FF=197). Compared with the FF group (100mg/day), PF group (0.05 to 0.4mg/day) had a better effect on reducing triglycerides (TGs) (MD, -8.66; 95%CI, -10.91 to -6.41), very low-density lipoprotein cholesterol (VLDL-C, MD, -12.19; 95%CI, -15.37 to - 9.01), remnant lipoprotein cholesterol (MD, -13.16; 95%CI, -17.62 to -8.69), apolipoprotein-B48 (ApoB48, MD, -12.74; 95%CI, -17.71 to -7.76) and ApoCIII (MD, -6.25; 95%CI, -11.85 to -0.64). Although a slightly LDL-Cincreasing effect was found in PF-treated group (MD, 3.10; 95%CI, -0.12 to 6.09), the levels of HDL-C (MD, 3.59; 95%CI, 1.65 to 5.53) and ApoAI (MD, 1.60; 95%CI, 0.38 to 2.82) were significantly increased in the PF group. However, no significant difference was found in the level of total cholesterol (MD, 0.01; 95%CI, -1.37 to - 1.39), non-HDL-C (MD, -0.06; 95%CI, -1.75 to 1.63), ApoB (MD, 0.39; 95%CI, -1.37 to 2.15) and ApoAII (MD, 3.31; 95%CI, -1.66 to 8.29) between the two groups. In addition, the incidence of total adverse events (OR, 0.68; 95%CI, 0.53 to 0.86) and adverse drug reactions (OR, 0.36; 95%CI, 0.24 to 0.54) was lower in the PF group than that in the FF group.

Conclusions: Pemafibrate tends to have better efficacy in treating dyslipidemia than fenofibrate.

Keywords: Pemafibrate, fenofibrate, lipid parameters, RCTs, adverse drug reactions, dyslipidemia.

[1]
Teramoto T, Sasaki J, Ishibashi S, et al. Japan Atherosclerosis Society (JAS). Comprehensive risk management for the prevention of cardiovascular disease: Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan 2012. J Atheroscler Thromb 2013; 20(7): 603-15.
[http://dx.doi.org/10.5551/jat.15867] [PMID: 23883545]
[2]
Ginsberg HN, Elam MB, Lovato LC, et al. ACCORD Study Group. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010; 362(17): 1563-74.
[http://dx.doi.org/10.1056/NEJMoa1001282] [PMID: 20228404]
[3]
Ahmad J, Odin JA, Hayashi PH, et al. Identification and characterization of fenofibrate-induced liver injury. Dig Dis Sci 2017; 62(12): 3596-604.
[http://dx.doi.org/10.1007/s10620-017-4812-7] [PMID: 29119413]
[4]
Usman M, Peter R. Fibrate therapy: safety considerations. Curr Opin Lipidol 2007; 18(6): 702-4.
[http://dx.doi.org/10.1097/MOL.0b013e3282f1ed84] [PMID: 17993818]
[5]
Araki E, Yamashita S, Arai H, et al. Effects of pemafibrate, a novel selective PPARa modulator, on lipid and glucose metabolism in patients with type 2 diabetes and hypertriglyceridemia: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 2018; 41: 538-46.
[http://dx.doi.org/10.2337/dc17-1589] [PMID: 29298800]
[6]
Araki E, Yamashita S, Arai H, et al. Efficacy and safety of pemafibrate in people with type 2 diabetes and elevated triglyceride levels: 52-week data from the PROVIDE study. Diabetes Obes Metab 2019; 21(7): 1737-44.
[http://dx.doi.org/10.1111/dom.13686] [PMID: 30830727]
[7]
Matsuba I, Matsuba R, Ishibashi S, et al. Effects of a novel selective peroxisome proliferator-activated receptor-α modulator, pemafibrate, on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance. J Diabetes Investig 2018; 9(6): 1323-32.
[http://dx.doi.org/10.1111/jdi.12845] [PMID: 29603684]
[8]
Araki M, Nakagawa Y, Oishi A, et al. The peroxisome proliferator-activated receptor α (PPARα) agonist pemafibrate protects against diet-induced obesity in mice. Int J Mol Sci 2018; 19(7): 19.
[http://dx.doi.org/10.3390/ijms19072148] [PMID: 30041488]
[9]
Ishibashi S, Yamashita S, Arai H, et al. Effects of K-877, a novel selective PPARα modulator (SPPARMα), in dyslipidaemic patients: a randomized, double blind, active- and placebo-controlled, phase 2 trial. Atherosclerosis 2016; 249: 36-43.
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.02.029] [PMID: 27062408]
[10]
Ishibashi S, Arai H, Yokote K, et al. Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia: Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial. J Clin Lipidol 2018; 12(1): 173-84.
[http://dx.doi.org/10.1016/j.jacl.2017.10.006] [PMID: 29203092]
[11]
Ida S, Kaneko R, Murata K. Efficacy and safety of pemafibrate administration in patients with dyslipidemia: A systematic review and meta-analysis. Cardiovasc Diabetol 2019; 18(1): 38.
[http://dx.doi.org/10.1186/s12933-019-0845-x] [PMID: 30898163]
[12]
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Ann Intern Med 2009; 151: 264-9.
[13]
Higgins JP, Altman DG, Gøtzsche PC, et al. The cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011; 343: d5928.
[http://dx.doi.org/10.1136/bmj.d5928] [PMID: 22008217]
[14]
Yin P, Ji Q, Wang Y, et al. Percutaneous kyphoplasty for osteoporotic vertebral compression fractures via unilateral versus bilateral approach: A meta-analysis. J Clin Neurosci 2019; 59: 146-54.
[http://dx.doi.org/10.1016/j.jocn.2018.10.112] [PMID: 30414813]
[15]
DerSimonian R, Laird N. Meta-analysis in clinical trials revisited. Contemp Clin Trials 2015; 45(Pt A): 139-45.
[http://dx.doi.org/10.1016/j.cct.2015.09.002] [PMID: 26343745]
[16]
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003; 327(7414): 557-60.
[http://dx.doi.org/10.1136/bmj.327.7414.557] [PMID: 12958120]
[17]
Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation 1998; 98(19): 2088-93.
[http://dx.doi.org/10.1161/01.CIR.98.19.2088] [PMID: 9808609]
[18]
Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, et al. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J 1996; 15(19): 5336-48.
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb00918.x] [PMID: 8895578]
[19]
Farnier M. Update on the clinical utility of fenofibrate in mixed dyslipidemias: mechanisms of action and rational prescribing. Vasc Health Risk Manag 2008; 4(5): 991-1000.
[http://dx.doi.org/10.2147/VHRM.S3390] [PMID: 19183747]
[20]
Ferri N, Corsini A, Sirtori C, Ruscica M. PPAR-α agonists are still on the rise: an update on clinical and experimental findings. Expert Opin Investig Drugs 2017; 26(5): 593-602.
[http://dx.doi.org/10.1080/13543784.2017.1312339] [PMID: 28343425]
[21]
Raza-Iqbal S, Tanaka T, Anai M, et al. Transcriptome analysis of K-877 (a novel Selective PPARα Modulator (SPPARMα))-regulated genes in primary human hepatocytes and the mouse liver. J Atheroscler Thromb 2015; 22(8): 754-72.
[http://dx.doi.org/10.5551/jat.28720] [PMID: 26040752]
[22]
Sairyo M, Kobayashi T, Masuda D, et al. A novel selective PPARα modulator (SPPARMα), K-877 (pemafibrate), attenuates postprandial hypertriglyceridemia in mice. J Atheroscler Thromb 2018; 25(2): 142-52.
[http://dx.doi.org/10.5551/jat.39693] [PMID: 28781340]
[23]
Yamashita S, Arai H, Yokote K, et al. Effects of pemafibrate (K-877) on cholesterol efflux capacity and postprandial hyperlipidemia in patients with atherogenic dyslipidemia. J Clin Lipidol 2018; 12: 1267-79.e4.
[24]
Arai H, Yamashita S, Yokote K, Araki E, Suganami H, Ishibashi S. Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia. Atherosclerosis 2017; 261: 144-52.
[http://dx.doi.org/10.1016/j.atherosclerosis.2017.03.032] [PMID: 28410749]
[25]
Arai H, Kokubo Y, Watanabe M, et al. Small dense low-density lipoproteins cholesterol can predict incident cardiovascular disease in an urban Japanese cohort: the Suita study. J Atheroscler Thromb 2013; 20(2): 195-203.
[http://dx.doi.org/10.5551/jat.14936] [PMID: 23076217]
[26]
Chancharme L, Thérond P, Nigon F, Lepage S, Couturier M, Chapman MJ. Cholesteryl ester hydroperoxide lability is a key feature of the oxidative susceptibility of small, dense LDL. Arterioscler Thromb Vasc Biol 1999; 19(3): 810-20.
[http://dx.doi.org/10.1161/01.ATV.19.3.810] [PMID: 10073990]
[27]
Masuda D, Sugimoto T, Tsujii K, et al. Correlation of fasting serum apolipoprotein B-48 with coronary artery disease prevalence. Eur J Clin Invest 2012; 42(9): 992-9.
[http://dx.doi.org/10.1111/j.1365-2362.2012.02687.x] [PMID: 22587365]
[28]
Taskinen MR, Borén J. Why Is Apolipoprotein CIII emerging as a novel therapeutic target to reduce the burden of cardiovascular disease? Curr Atheroscler Rep 2016; 18(10): 59.
[http://dx.doi.org/10.1007/s11883-016-0614-1] [PMID: 27613744]
[29]
Cui Y, Blumenthal RS, Flaws JA, et al. Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Arch Intern Med 2001; 161(11): 1413-9.
[http://dx.doi.org/10.1001/archinte.161.11.1413] [PMID: 11386890]
[30]
Pischon T, Girman CJ, Sacks FM, Rifai N, Stampfer MJ, Rimm EB. Non-high-density lipoprotein cholesterol and apolipoprotein B in the prediction of coronary heart disease in men. Circulation 2005; 112(22): 3375-83.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.104.532499] [PMID: 16316964]
[31]
Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis 2016; 253: 281-344.
[http://dx.doi.org/10.1016/j.atherosclerosis.2016.08.018] [PMID: 27594540]
[32]
Honda Y, Kessoku T, Ogawa Y, et al. Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, improves the pathogenesis in a rodent model of nonalcoholic steatohepatitis. Sci Rep 2017; 7: 42477.
[http://dx.doi.org/10.1038/srep42477] [PMID: 28195199]
[33]
Blair HA. Pemafibrate: first global approval. Drugs 2017; 77(16): 1805-10.
[http://dx.doi.org/10.1007/s40265-017-0818-x] [PMID: 28929345]
[34]
Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet 2005; 366(9500): 1849-61.
[http://dx.doi.org/10.1016/S0140-6736(05)67667-2] [PMID: 16310551]
[35]
Pradhan AD, Paynter NP, Everett BM, et al. Rationale and design of the pemafibrate to reduce cardiovascular outcomes by reducing triglycerides in patients with diabetes (PROMINENT) study. Am Heart J 2018; 206: 80-93.
[http://dx.doi.org/10.1016/j.ahj.2018.09.011] [PMID: 30342298]


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VOLUME: 25
ISSUE: 44
Year: 2019
Page: [4725 - 4734]
Pages: 10
DOI: 10.2174/1381612825666191126102943
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