Page 26 - BH-1-2

Brain & Heart Pemafibrate in patients with dyslipidemia

4. Discussion administered twice daily, respectively, and 34.0%, 37.7%,
and 42.7% at dosages of 0.1 mg, 0.2 mg, and 0.4 mg when
In this systematic review and meta-analysis, we compared administered once daily. Importantly, these reductions
pemafibrate to either placebo or fenofibrate in patients exhibited no significant gender disparities. Furthermore, in
with hypertriglyceridemia, synthesizing data from nine an exploratory analysis involving the subgroup of patients
RCTs involving 12,644 participants. Of all participants, with type 2 diabetes mellitus, no discernible differences in
6699 (53%) received the pemafibrate. The main findings treatment outcomes or drug interactions were observed
were as follows: (i) The percent reduction in total TG within this population .
[25]
significantly improved with all dosages of pemafibrate
compared with placebo; (ii) non-HDL levels were The findings from Ginsberg et al. revealed that
significantly lower in patients treated with pemafibrate at pemafibrate at 0.2 mg twice a day was associated with a
the dose of 0.4 mg/day compared to placebo; and (iii) there 2.6% reduction in fasting blood sugar levels, whereas
was no significant percent change in TG between patients the placebo caused a 5.2% increase. Insulin resistance,
treated with pemafibrate at 0.2 mg/day and those treated estimated using homeostatic model assessment (HOMA),
with fenofibrate at 200 mg/day. and exhibited changes of 0.33% on placebo and 1.74%
on pemafibrate at 0.2 mg twice daily. The placebo group’s
It is worth emphasizing that Ida et al. conducted HOMA of insulin resistance improved by 0.33%, whereas
[28]
a prior meta-analysis on this subject, encompassing those administered pemafibrate at 0.2 mg twice a day
1623 patients. However, their analysis was completed showed an improvement of 1.74% . On the other hand,
[25]
before the completion of the PROMINENT study, Arai et al. suggested that pemafibrate medication may
a substantial clinical trial designed to evaluate the contribute to improving insulin resistance, although
impact of administering pemafibrate on cardiovascular additional research is needed .
[15]
outcomes [18,23,24,28] . In contrast, our present meta-
analysis incorporates data from the PROMINENT trial, In the study conducted by Araki et al., fasting blood
significantly strengthening our analysis with an additional TG levels were statistically significantly lower in both
10,497 patients and providing more recent evidence. pemafibrate groups (0.2 mg/day and 0.4 mg/day) compared
to the placebo group (P < 0.001, multiplicity adjusted). No
The PROMINENT trial enrolled individuals with noticeable gender differences were observed. Notably, TG
type 2 diabetes, mild-to-moderate hypertriglyceridemia, levels showed a considerable decrease in each pemafibrate
low HDL-C, and well-controlled LDL cholesterol group starting from week 4, and this significance persisted
levels. This randomized, double-blinded, and placebo- until week 24 .
[24]
controlled study revealed that the pemafibrate group
exhibited reductions in TG, very-low-density lipoprotein In our meta-analysis, we observed that the pemafibrate
cholesterol, residual cholesterol, and apolipoprotein C-III. group exhibited lower TG levels and higher HDL-C
Surprisingly, there was no significant disparity in the levels compared to the placebo group. However, when
frequency of cardiovascular events between those who comparing pemafibrate to fenofibrate, no statistically
received pemafibrate and those administered a placebo. significant difference was found. Regarding drug safety,
Notably, discernible heterogeneity in treatment effects the incidence of increased hepatobiliary enzyme activity
was notably lower in the pemafibrate group compared to
across various patient subgroups identified in the study both the placebo and fenofibrate groups. Interestingly, the
was not observed .
[18]
pemafibrate group displayed an increase in hepatobiliary
According to the findings of the trial conducted by enzyme activity, likely attributed to pemafibrate’s activation
Ishibashi et al., pemafibrate has demonstrated a notable of PPAR, which is known to accelerate fatty acid oxidation,
reduction of approximately 46% in fasting serum TG levels thereby promoting energy expenditure in the liver and
among dyslipidemic patients with high TG and low HDL-C reducing fat storage .
[28]
levels. The study also suggested that pemafibrate was more According to our meta-analysis, patients treated with
effective than fenofibrate (106.6 mg/day), although this pemafibrate at 0.4 mg/day exhibited considerably lower
difference may be attributed to the fact that the pemafibrate non-HDL-C levels compared to those on a placebo.
group had almost twice as many subjects .
[16]
Examination of the 0.1 mg/day and 0.2 mg/day doses
In the trial conducted by Ginsberg et al., a comparison of pemafibrate and placebo did not reveal substantially
between pemafibrate and a placebo demonstrated different reductions in non-HDL-C levels. In the study
notable reductions in fasting serum triglyceride (TG) by Ginsberg et al., twice-daily pemafibrate resulted in
concentrations. Specifically, these reductions were 36.1%, placebo-adjusted, dose-dependent decreases in fasting
45.8%, and 54.4% at dosages of 0.05 mg, 0.1 mg, and 0.2 mg non-HDL-cholesterol concentrations of 6.8%, 7.4%, and

Volume 1 Issue 2 (2023) 10 https://doi.org/10.36922/bh.1629