Efficacy and safety of pemafibrate administration in patients with dyslipidemia: a systematic review and meta-analysis

Abstract

BackgroundUsing a meta-analysis of randomized controlled trials (RCTs), this study aimed to investigate the efficacy and safety of pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia.MethodsA search was performed using the MEDLINE, Cochrane Controlled Trials Registry, and ClinicalTrials.gov databases. We decided to employ RCTs to evaluate the effects of pemafibrate on lipid and glucose metabolism-related parameters in patients with dyslipidemia. For statistical analysis, standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CIs) were calculated using the random effect model.ResultsOur search yielded seven RCTs (with a total of 1623 patients) that satisfied the eligibility criteria of this study; hence, those studies were incorporated into this meta-analysis. The triglyceride concentration significantly decreased in the pemafibrate group (SMD, − 1.38; 95% CI, − 1.63 to − 1.12; P < 0.001) than in the placebo group, with a reduction effect similar to that exhibited by fenofibrate. Compared with the placebo group, the pemafibrate group also showed improvements in high-density and non-high-density lipoprotein cholesterol levels as well as in homeostasis model assessment for insulin resistance. Furthermore, the pemafibrate group showed a significant decrease in hepatobiliary enzyme activity compared with the placebo and fenofibrate groups; and, total adverse events (AEs) were significantly lower in the pemafibrate group than in the fenofibrate group (OR, 0.60; 95% CI, 0.49–0.73; P < 0.001). In contrast, the low-density lipoprotein cholesterol level was significantly higher in the pemafibrate group than in the placebo (P = 0.006) and fenofibrate (P < 0.001) groups.ConclusionsThe lipid profile significantly improved in the pemafibrate group than in the placebo group. In addition to the pemafibrate group having an improved lipid profile, which was comparable with that of the fenofibrate group, the AEs were significantly lower than in the fenofibrate group and an improvement in hepatobiliary enzyme activity was also recognized. However, we believe that actual clinical data as well as long-term efficacy and safety need to be investigated in the future.Electronic supplementary materialThe online version of this article (10.1186/s12933-019-0845-x) contains supplementary material, which is available to authorized users.

Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study

“…Other studies suggest that fibrates may also have beneficial effects on microvascular outcomes, including During the trial period, fibrate add-on therapy reduced triglycerides and VLDL-C beyond that achieved with statins only, but HDL-C was increased by only a limited amount. These findings have been observed in other clinical trials of fibrate-for example in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, allocation to fenofibrate resulted in a 20% reduction of baseline TG, but HDL-C remained almost unchanged at study close [30][31][32]. The improvement of the triglyceriderich environment may explain the reduced risk of CVD observed during the trial period in these patients [15,33].…”

Combination Therapy with Pemafibrate (K-877) and Pitavastatin Improves Vascular Endothelial Dysfunction in Dahl/Salt-sensitive Rats Fed a High-salt and High-fat Diet​

“…This study also showed that pema brate decreased TG, including total, CM, VLDL, and HDL-TG, and cholesterol, including total, VLDL, and LDL, in dyslipidemic rats with high TG and high cholesterol levels. A recent meta-analysis also revealed that pema brate signi cantly reduced TG levels [31]. Takei et al reported that pema brate (K-877) is a potential PPARα-modulating drug to treat hyperlipidemia that works well in both the liver and small intestine of LDL receptor knockout (Ldlr -/-) mice [32].…”

Predictive values of ANGPTL8 on risk of all-cause mortality in diabetic patients: results from the REACTION Study

“…This effect, combined with abnormal metabolism of glucose, high incident rates of hypertension and renal dysfunction, and increased BMI, might contribute together to atherosclerosis, cardiovascular diseases and death in diabetic patients. ANGPTL8 is related to HDL-C dysfunction and is involved in the association between dyslipidaemia and arteriosclerosis [27], regardless of glucose intolerance or diabetes mellitus [43,44]. ANGPTL8 presents a negative effect on HDL-mediated cholesterol e ux capacity [17] and a strong link with subclinical atherosclerosis [27], and its levels are signi cantly increased in patients with coronary disease, proportional to disease severity [45].…”