Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).
OBJECTIVE
High plasma triglyceride (TG) is an independent risk factor for cardiovascular disease. Fibrates lower TG levels through peroxisome proliferator–activated receptor α (PPARα) agonism. Currently available fibrates, however, have relatively low selectivity for PPARα. The aim of this trial was to assess the safety, tolerability, and efficacy of K-877 (pemafibrate), a selective PPARα modulator, in statin-treated European patients with hypertriglyceridemia.
RESEARCH DESIGN AND METHODS
A total of 408 statin-treated adults were recruited from 68 European sites for this phase 2, randomized, double-blind, placebo-controlled trial. They had fasting TG between 175 and 500 mg/dL and HDL-cholesterol (HDL-C) ≤50 mg/dL for men and ≤55 mg/dL for women. Participants were randomly assigned to receive placebo or one of six pemafibrate regimens: 0.05 mg twice a day, 0.1 mg twice a day, 0.2 mg twice a day, 0.1 mg once daily, 0.2 mg once daily, or 0.4 mg once daily. The primary end points were TG and non–HDL-C level lowering at week 12.
RESULTS
Pemafibrate reduced TG at all doses (adjusted P value <0.001), with the greatest placebo-corrected reduction from baseline to week 12 observed in the 0.2-mg twice a day treatment group (54.4%). Reductions in non–HDL-C did not reach statistical significance. Reductions in TG were associated with improvements in other markers for TG-rich lipoprotein metabolism, including reductions in apoB48, apoCIII, and remnant cholesterol and an increase in HDL-C levels. Pemafibrate increased LDL-cholesterol levels, whereas apoB100 was unchanged. Pemafibrate was safe and well-tolerated, with only minor increases in serum creatinine and homocysteine concentrations.
CONCLUSION
Pemafibrate is effective, safe, and well-tolerated for the reduction of TG in European populations with hypertriglyceridemia despite statin treatment.
<strong>Background </strong>High plasma
triglyceride (TG) is an independent risk factor for cardiovascular disease. Fibrates lower TG-levels through
PPARα agonism. Currently available fibrates, however, have relatively low
selectivity for PPARα.<b></b>
<p><strong>Objectives</strong> The aim of this
trial was to assess the safety, tolerability and efficacy of K-877
(pemafibrate) —a selective PPARα modulator —in statin-treated European
patients with hypertriglyceridemia.<b></b></p>
<p><strong>Methods A total of </strong>408 statin-treated
adults were recruited from 68 European sites for this Phase 2, randomized,
double-blind, placebo-controlled trial. They had fasting TG between 175 and 500
mg/dL and HDL-C ≤50 mg/dL for men and ≤55 mg/dL for women. Participants were
randomized to receive placebo or one of 6 pemafibrate regimens: 0.05 mg BID, 0.1
mg BID, 0.2 mg BID, 0.1 mg QD, 0.2 mg QD, or 0.4 mg QD. The primary endpoints were TG and non-HDL-C level lowering at Week 12.<b></b></p>
<p><b>Results</b><b></b></p>
<p>Pemafibrate
reduced TG at all doses (adjusted p value <0.001) with the greatest
placebo-corrected reduction from baseline to Week 12 observed in the 0.2 mg BID
treatment group (54.4%). Reductions in non-HDL-C did not reach statistical
significance. Reductions in TG were associated with improvements in other
markers for TG-rich lipoprotein metabolism, including reductions in apoB48,
apoCIII, and remnant cholesterol, and an increase in HDL-C levels.
Pemafibrate
increased LDL-C levels,
whereas apoB100 was unchanged.
Pemafibrate was safe and well-tolerated, with only minor increases in serum
creatinine and homocysteine concentrations.</p>
<p><b>Conclusion</b></p>
<p>Pemafibrate is effective, safe, and
well-tolerated for the reduction of TG in European populations with
hypertriglyceridemia despite statin treatment.</p>
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.