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Brain & Heart Pemafibrate in patients with dyslipidemia

1. Introduction help mitigate the deleterious side effects commonly
associated with traditional fibrates, such as hepatotoxicity,
Dyslipidemia is a chronic pathological condition myopathy, and renal impairment. Pemafibrate’s unique
characterized by abnormal lipid levels in the bloodstream. pharmacological profile suggests distinct advantages
This condition is widely acknowledged as a significant over other fibrates in terms of safety and effectiveness,
risk factor for atherosclerotic cardiovascular disease positioning it as a prospective treatment alternative
(ASCVD) and mortality on a global scale, due to its for patients with dyslipidemia and other metabolic
alarming prevalence [1,2] . Consequently, a comprehensive diseases [15,16] . Importantly, pemafibrate has demonstrated
evaluation of an individual’s cardiovascular risk requires a favorable safety record for patients concurrently
the consideration of multiple variables, including low- using statins and for those with chronic kidney disease,
density lipoprotein cholesterol (LDL-C) levels, a parameter underscoring its potential as a significant treatment
frequently employed in clinical settings. Statins and lifestyle alternative .
[17]
changes to lower LDL-C levels are critical in managing
these high-risk patients [3,4] . Nonetheless, statin therapy Consequently, the objective of this systematic review
alone has a 20% benefit in preventing the development and meta-analysis is to furnish an updated investigation
of cardiovascular diseases such as myocardial infarction into the efficacy of pemafibrate, with a specific focus on
or ischemic stroke, leaving patients with an estimated evaluating the impact of this therapy on lipid profile and
residual risk of 80% [5,6] . Hence, identifying additional adverse events. This analysis holds particular significance
pharmacologic methods that can minimize the overall risk in light of the considerable attention that this drug has
of cardiovascular disease has become increasingly relevant. received as a potential game-changer in the management
of dyslipidemia due to its previously discussed unique
High triglyceride (TG) levels and low high-density pharmacological profile. Nevertheless, it is critical to
lipoprotein cholesterol (HDL-C) levels in serum have underscore recent findings from the PROMINENT
consistently been demonstrated to have a strong and trial, which failed to reveal a substantial reduction in
independent connection with an elevated risk of developing cardiovascular events despite the drug’s favorable effects
ASCVD [6-9] . However, a definitive causal relationship has on lipid markers. This contrast highlights the need
yet to be established in the literature. Nonetheless, statins, for a comprehensive assessment of its overall clinical
primarily targeting the HMG-CoA reductase pathway, impact [18] .
exhibit a restricted capacity to induce significant alterations
in TG and HDL-C levels among individuals grappling with 2. Materials and methods
severe dyslipidemia . In contrast, fibrates, also known
[10]
as peroxisome proliferator-activated receptor α (PPARα) 2.1. Search strategy
activators, are a well-established therapeutic option The study design in this research adhered to the Preferred
for managing dyslipidemia in patients with markedly Reporting Items for Systematic Reviews and Meta-Analysis
elevated TG that does not respond adequately to statin Protocol (PRISMA) . To ensure transparency and
[19]
therapy. In these cases, fibrates are specifically indicated adherence to best practices, we also utilized PROSPERO
to minimize the risk of pancreatitis. They also effectively (International prospective registration of systematic
increase HDL-C levels, which is potentially beneficial [11,12] . reviews) to register the pre-specified study procedure (ID:
Few meta-analyses have reported certain benefits of CRD42022374852).
prescribing fibrates to prevent cardiovascular disease in A comprehensive search was conducted across the
[13]
this specific population . However, fibrates, especially MEDLINE (through PubMed), EMBASE, and Cochrane
when administered concurrently with statins, can lead to a Library databases, encompassing data from their creation
number of potentially serious side effects, including hepatic up to March 11, 2023. The search strategy employed
or kidney dysfunction, myopathy, and rhabdomyolysis, a methodical approach to identify all relevant trials
which can compromise drug administration and treatment that reported the use of pemafibrate in patients with
adherence . dyslipidemia. The search strategy (employing medical
[14]
Accordingly, a novel drug, pemafibrate, a selective subject heading terms) was as follows: (dyslipidemia
PPARα modulator (SPPARMα), has garnered significant OR dyslipidemias OR dyslipidemic OR dyslipidemia OR
attention from the medical community. This heightened cholesterol OR triglycerides [TG] OR HDL OR LDL OR
interest is primarily attributed to its high selectivity “high-density lipoprotein” OR “low-density protein”)
for PPAR subtypes, including PPARα1 and PPARα2, AND (pemafibrate OR K-877 OR SPPARMα OR
while avoiding activation of other PPAR subtypes such “selective peroxisome proliferator-activated receptor”
as PPARβ/δ and PPARγ. This selectivity is believed to OR “selective modulator of peroxisome proliferator-

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