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Brain & Heart Pemafibrate in patients with dyslipidemia

activated receptor” OR “selective PPAR” OR “selective levels (measured mmol/L and mg/dL), and adverse events
modulator of PPAR”) AND (random OR randomized OR (allergic reactions, liver injury, and elevated creatine
randomized OR RCT OR “Controlled Clinical Trial”). The phosphokinase levels).
complete electronic search strategy can be summarized
as: (Dyslipidemia OR dyslipidemias OR dyslipidemia 2.4. Risk of bias assessment
OR dyslipidemic OR dyslipidemia OR cholesterol OR The risk of bias for each study included in the analysis was
TG OR HDL OR LDL OR “high-density lipoprotein” evaluated using the Cochrane risk of bias assessment tool,
OR “low-density protein”) AND (pemafibrate OR in accordance with the recommended criteria provided
“K-877” OR “SPPARMα” OR “selective peroxisome in the Cochrane Handbook for Systematic Reviews of
proliferator-activated receptor” OR “selective modulator Interventions [20,21] . This evaluation was performed by five
of peroxisome proliferator-activated receptor” OR independent investigators (C.C.A.B., M.M.G., M.E.B.,
“selective PPAR” OR “selective modulator of PPAR”) L.M.F., and B.P.A.G.), and the results were documented
AND (random OR randomized OR randomized OR in a risk of bias table. Any discrepancies or doubts
RCT OR “Controlled Clinical Trial”). discovered during the assessment process were resolved in
consultation with the senior author (N.N.L.).
2.2. Inclusion criteria and data extraction
In the evaluation of the papers under consideration, no 2.5. Data analysis
restrictions were imposed on publication date, language, In our meta-analyses for continuous outcomes, we utilized
or publishing status. Studies were deemed eligible for the mean difference (MD) method, with corresponding
inclusion in this meta-analysis if they met the following 95% confidence intervals (CI) serving as indicators
criteria: (i) Being randomized controlled trials (RCTs); (ii) of the effect size. To assess heterogeneity, we utilized
featuring at least one study arm using pemafibrate; (iii) Cochrane’s Q statistic and Higgins and Thompson’s I²
including a control group; (iv) involving patients of all age statistic. Furthermore, all outcome analyses underwent
groups diagnosed with any form of dyslipidemia; and (v) random-effects meta-analyses using the DerSimonian-
reporting on at least one of the clinical outcomes of interest. Laird method. The statistical analysis was conducted using
Studies were excluded if they lacked a placebo or Review Manager 5.4 (The Nordic Cochrane Centre, The
[22]
fenofibrate control group or if they presented duplicated Cochrane Collaboration, Denmark) .
data. In cases of data duplication, the study with the Subgroup analyses were prespecified as follows:
larger sample size was chosen. Initially, studies of interest Pemafibrate at a dosage of 0.4 mg/day compared to
underwent a pre-selection process for full-text review. placebo, pemafibrate at 0.2 mg/day compared to placebo
Supplementary materials were reviewed in instances (HDL, LDL, non-HDL, TG, and TC levels), pemafibrate
where the publication did not report the desired outcomes at 0.2 mg/day compared to fenofibrate (TG levels), and
(particularly lipid profile endpoints). Article selection pemafibrate at 0.1 mg/day compared to placebo (HDL,
and data extraction were undertaken independently by at LDL, non-HDL, TG, and TC levels).
least two reviewers (Caroline Cristine Almeida Balieiro
and Marcela Mizuhira Gobbo). Any disagreements that 3. Results
arose were resolved through author consensus following a
thorough examination of the entire manuscript alongside 3.1. Study selection and characteristics
the senior author (N.N.L.). The search strategy yielded a total of 184 results, as shown
in Figure 1. Following a meticulous assessment based on
2.3. Variables of interest and their outcomes inclusion and exclusion criteria, 22 papers were retained
The studies yielded the following information: (i) Research for full-text evaluation, with ineligible and duplicate studies
parameters: research design, number of participants per having been excluded from the study. Among these papers,
group, study population, time to follow-up, pemafibrate non-randomized trials and studies with overlapping patient
dosage, and control type (placebo or fenofibrate) and populations were further excluded from the analysis.
respective dos age; (ii) patient characteristics: age, body Consequently, a total of 9 RCTs involving 12,644 patients
mass index (BMI), presence of type 2 diabetes, systemic were included in our study. Pemafibrate was administered
arterial hypertension, and statin use before intervention; to 6699 (53%) individuals. The mean age across these trials
(3) clinical outcomes: triglyceride levels (measured ranged from 46.4 to 64 years, and 11,168 (88.3%) patients
in mmol/L and mg/dL), non-HDL cholesterol levels had diabetes. A comprehensive summary of the studies
(measured in mmol/L and mg/dL), LDL cholesterol levels and their respective research characteristics is provided in
(measured in mmol/L and mg/dL), total cholesterol (TC) Table 1.

Volume 1 Issue 2 (2023) 3 https://doi.org/10.36922/bh.1629