Page 27 - BH-1-2

Brain & Heart Pemafibrate in patients with dyslipidemia

8.9% at dosages of 0.05 mg, 0.1 mg, and 0.2 mg twice daily. and non-HDL, revealed notable heterogeneity stemming
Similarly, once-daily pemafibrate reduced fasting non- from the study conducted by Ishibashi et al. Several
[26]
HDL-C levels by 5.2% at 0.1 mg, 9.1% at 0.2 mg, and 7.8% factors contribute to this observed variability. First, the
at 0.4 mg in a placebo-controlled study. However, despite study systematically excluded patients with liver failure,
the statistically significant difference in the percentage of renal failure, and diabetes mellitus, conditions commonly
LDL-C decreases between the K-877 0.2 mg/day group and encountered in clinical settings involving patients with
the placebo group, the mean LDL-C remained essentially dyslipidemia. Second, the study cohort exclusively
unaltered . In patients with hypertriglyceridemia, the comprised patients with Japanese heritage, thereby raising
[23]
calculated LDL could be falsely lower due to high TG levels concerns about the generalizability of the findings to
(calculation of [LDL] =[TC] -[HDL] -[TG]/5) and may not individuals of other ethnicities.
provide reliable levels. For these patients, assessment with
non-HDL-C will be useful as it does not consider TG in 5. Conclusion
the calculation. Based on the findings of our comprehensive review

Pemafibrate has demonstrated effectiveness in reducing and meta-analysis, it is evident that pemafibrate at
insulin resistance by lowering fasting blood glucose and 0.4 mg/day significantly reduces TG and non-HDL
fasting insulin levels across various studies . The positive levels in patients with dyslipidemia when compared to
[16]
outcomes of pemafibrate extend to the reduction of lipid placebo. Furthermore, in light of the neutral conclusion
buildup and oxidative stress in the kidney , suggesting its derived from our review of the PROMINENT trial, it
[24]
potential to mitigate significant and devastating diabetic becomes evident that additional research is required to
microvascular consequences. This potential is attributed to ascertain the comprehensive impact of pemafibrate on
the enhanced selectivity and efficacy of this SPPARM drug, cardiovascular events and mortality. Consequently, our
coupled with evidence of anti-inflammatory properties . findings emphasize the imperative for further studies to
[17]
However, it is important to note that the present study did enhance our understanding and obtain a comprehensive
not evaluate these findings, indicating the need for more knowledge of pemafibrate’s potential benefits in lowering
thorough research. cardiovascular risk.
In the trial conducted by Ginsberg et al. , pemafibrate Acknowledgments
[25]
administered at a dose of 0.2 mg twice daily, significantly
increased serum creatinine concentrations when added The development of this research was only possible with
to statin therapy alone compared to placebo. In addition, the guidance of Rhanderson Cardoso, MD.
the largest rise (3.8% vs. placebo) was far lower than
those reported for comparable fenofibrate doses (5 – Funding
22%) and was comparable to elevations observed in other None.
pemafibrate investigations, including a study conducted in
individuals with impaired renal function. Importantly, the Conflict of interest
effects of fenofibrate on glomerular filtration rate measured All authors report no relationships that could be construed
in the ACCORD and FIELD trials were found to be totally as a conflict of interest. All authors take responsibility for
reversible after treatment termination, even after several all aspects of the reliability and freedom from bias of the
years of active therapy [29,30] .
data presented and their discussed interpretation.
Our study has certain limitations. Notably, we observed
significant heterogeneity throughout the analyses, a factor Author contributions
that may have influenced the overall results. Therefore, a Conceptualization: Caroline Cristine Almeida Balieiro,
leave-one-out sensitivity analysis was performed to analyze Noah Romero Nakajima
the weight of each individual study on heterogeneity. The Formal analysis: Caroline Cristine Almeida Balieiro, Maria
analyses involving the PROMINENT trial exhibited overall Esther Barbalho, Luiza Mendes Fonseca
high heterogeneity, possibly attributed to its substantial Investigation: Caroline Cristine Almeida Balieiro, Marcela
sample size. This can be rationalized by the substantial Mizuhira Gobbo, Beatriz Polachini Assunes Gonçalves
heterogeneity within the population under scrutiny, Writing – original draft: Caroline Cristine Almeida Balieiro,
encompassing variations in demographic attributes, medical Maria Esther Barbalho, Luiza Mendes Fonseca
background, illness severity, and treatment responses . Writing – review & editing: Eduardo Cesar Teixeira Sirena,
[18]
The analysis comparing pemafibrate at a dose of 0.2 mg/ Alice D. Marinho, Matheus J. B. Moreira, Natália
day with fenofibrate, specifically in terms of reducing TG Nóbrega de Lima

Volume 1 Issue 2 (2023) 11 https://doi.org/10.36922/bh.1629