Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk

Pradhan, Aruna D.; Glynn, Robert J.; Fruchart, Jean‐Charles; MacFadyen, Jean; Zaharris, Elaine; Everett, Brendan M.; Campbell, Stuart; Oshima, Ryu; Amarenco, Pierre; Blom, Dirk; Brinton, Eliot A.; Eckel, Robert H.; Elam, Marshall B.; Felício, João Soares; Ginsberg, Henry N.; Goudev, Assen; Ishibashi, Shun; Joseph, Jacob; Kodama, Tatsuhiko; Köenig, Wolfgang; Leiter, Lawrence A.; Lorenzatti, Alberto; Mankovsky, Boris; Marx, Nikolaus; Nordestgaard, Børge G.; Páll, Dénes; Ray, Kausik K.; Santos, Raul D.; Soran, Handrean; Сусеков, А. В.; Tendera, Michał; Yokote, Koutaro; Paynter, Nina P.; Buring, Julie E.; Libby, Peter; Ridker, Paul M.

doi:10.1056/nejmoa2210645

Cited by 343 publications

(233 citation statements)

References 25 publications

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“…In the PROMINENT study, a sub-group analysis using the existence of heart failure was not investigated. Similar sub-group analyses were performed in the previous other studies [6]. The FIELD study demonstrated that the history of cardiovascular diseases and age were associated with incremental risk of cardiovascular events during femofibrate therapy [14].…”

Section: Factors That Were Associated With Cardiovascular Eventsmentioning

confidence: 54%

“…The study participants had received moderate-or strong-intensity statin, had low density lipoprotein cholesterol < 70 mg/dL, or had statin intolerance with low density lipoprotein cholesterol < 100 mg/dL. However, the addition of pemafibrate therapy was not superior to the standard of care in this trial [6].…”

Section: Introductionmentioning

confidence: 86%

“…Despite these promising findings, the PROMINENT trial did not demonstrate the benefit of pemafibrate therapy in reducing the risk of adverse cardiovascular events among patients with diabetes mellitus and hypertriglyceridemia [6]. Nevertheless, there may be a subgroup of patients on pemafibrate therapy that would be at high risk of adverse cardiovascular events compared to others due to differences in baseline characteristics.…”

Section: Factors That Were Associated With Cardiovascular Eventsmentioning

confidence: 98%

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Patient Selection for Pemafibrate Therapy to Prevent Adverse Cardiovascular Events

Izumida

Imamura

Narang

et al. 2022

JCM

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Background: pemafibrate is a newly-introduced selective peroxisome proliferator-activated receptor-α modulator, which decreases serum triglyceride levels with few drug-related adverse events and may reduce the risk of adverse cardiovascular events in carefully selected patients with hypertriglyceridemia. We aimed to understand which specific cohorts may benefit or not from pemafibrate therapy for adverse cardiovascular event risk reduction. Methods: patients with hypertriglyceridemia at baseline received pemafibrate therapy for two years or until October 2022. The factors that were associated with an increased risk of adverse cardiovascular events, defined as heart failure hospitalization, stroke, and acute coronary syndromes, were investigated. Results: a total of 121 patients (median 62 years, 88 men) remained on pemafibrate therapy for a median of 566 days without any drug-related adverse events. During a 3-month therapeutic period, triglyceride levels improved significantly from 302 (205, 581) mg/dL to 178 (117, 253) mg/dL (p < 0.001). During the overall therapeutic period, there were nine cardiovascular events. Comorbid chronic heart failure, comorbid coronary disease, and a lower pemafibrate dosing were independently associated with the primary endpoint (p < 0.05 for all). Those with multiple risk factors (N = 30) had a significantly higher cumulative incidence of the primary endpoint as compared with others (27% versus 3%, p < 0.001). Conclusion: pemafibrate significantly improves hypertriglyceridemia. A higher dose of pemafibrate should be considered to reduce the risk of adverse cardiovascular events, particularly in patients with chronic heart failure or coronary disease.

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Section: Factors That Were Associated With Cardiovascular Eventsmentioning

confidence: 54%

Section: Introductionmentioning

confidence: 86%

Section: Factors That Were Associated With Cardiovascular Eventsmentioning

confidence: 98%

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Patient Selection for Pemafibrate Therapy to Prevent Adverse Cardiovascular Events

Izumida

Imamura

Narang

et al. 2022

JCM

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“…Just recently, the results of the PROMINENT trial, which prospectively examined the preventive effects of pemafibrate on cardiovascular events among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL-C and LDL-C levels were published ( 72 ). In this trial, pemafibrate was expected to reduce cardiovascular events compared to placebo, however, the study failed to verify it.…”

Section: Discussionmentioning

confidence: 99%

The effects of pemafibrate and omega-3 fatty acid ethyl on apoB-48 in dyslipidemic patients treated with statin: A prospective, multicenter, open-label, randomized, parallel group trial in Japan (PROUD48 study)

Takeda

Sakuma²,

Hiramitsu³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundWe compared the lowering effects of pemafibrate and omega-3 fatty acid ethyl on fasting apolipoprotein (apo) B-48 (apoB-48), a marker that reflects postprandial hypertriglyceridemia, which is one of the residual risks for atherosclerotic cardiovascular disease (ASCVD) with statin treatment.MethodsThis prospective, multicenter, open-label, randomized, parallel group trial was conducted at 4 medical institutions between April 2020 and May 2022. A total of 126 ambulatory patients with dyslipidemia receiving statin treatment for more than 4 weeks, aged 20–79 years with fasting triglyceride (TG) levels of ≥177 mg/dl were randomly assigned to 16-week pemafibrate 0.4 mg per day treatment group (PEMA, n = 63) or omega-3 fatty acid ethyl 4 g per day treatment group (OMEGA-3, n = 63). The primary endpoint was the percentage change in fasting apoB-48 from baseline to week 16.ResultsThe percentage changes in fasting apoB-48 in PEMA and OMEGA-3 were −50.8% (interquartile range −62.9 to −30.3%) and −17.5% (−38.3 to 15.3%) (P < 0.001), respectively. As the secondary endpoints, the changes in fasting apoB-48 in PEMA and OMEGA-3 were −3.10 μg/ml (−5.63 to −1.87) and −0.90 μg/ml (−2.95 to 0.65) (P < 0.001), respectively. Greater decreases with significant differences in the percentage changes in TG, remnant lipoprotein cholesterol, apoC-III, fasting plasma glucose, alanine aminotransferase, gamma-glutamyl transpeptidase, and alkaline phosphatase were observed in PEMA, compared with OMEGA-3. Greater increases with significant differences in those in high-density lipoprotein (HDL) cholesterol, apoA-I, and apoA-II were observed in PEMA, compared with OMEGA-3. PEMA showed anti-atherosclerotic lipoprotein profiles in gel-permeation high-performance liquid chromatography analyses, compared with OMEGA-3. Although adverse events occurred in 9 of 63 (14.3%) patients in PEMA and 3 of 63 (4.8%) patients in OMEGA-3, no serious adverse events associated with drug were observed in either group.ConclusionsThis is the first randomized trial to compare the lowering effects of pemafibrate and omega-3 fatty acid ethyl on fasting apoB-48. We concluded that pemafibrate was superior to omega-3 fatty acid ethyl in lowering effect of fasting apoB-48. Pemafibrate is expected to reduce the residual risk for ASCVD with statin treatment.Clinical trial registrationhttps://rctportal.niph.go.jp/en, identifier jRCTs071200011.

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“… 50 However, in the most recently published the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes trial, pemafibrate treatment did not reduce the risk of CVD in patients with T2DM and dyslipidemia, in whom 95.7% of the study population were already receiving statins, even though it significantly reduced triglyceride, very-low-LDL-C, measured remnant cholesterol, and apolipoprotein C-III levels. 51 This suggests that triglyceride-lowering treatment using fibrates has limitations in reducing the risk of residual CVD.…”

Section: Treatmentsmentioning

confidence: 99%

Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement

Yang

Kim

et al. 2023

J Lipid Atheroscler

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Dyslipidemia in patients with diabetes is an important treatment target as a modifiable risk factor for cardiovascular disease (CVD). Although the primary treatment goal for dyslipidemia is to control low-density lipoprotein cholesterol (LDL-C), achieving this goal remains suboptimal according to recent studies. It is important to set the target goal for LDL-C control based on an accurate risk assessment for CVD. Here, we summarize the latest evidence on lipid management in patients with diabetes and present a consensus of the Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis on the treatment goals of LDL-C according to the duration of diabetes, presence of CVD, target organ damage, or major cardiovascular risk factors. In patients with type 2 diabetes mellitus (T2DM) and CVD, an LDL-C goal of <55 mg/dL and a reduction in LDL-C level by 50% or more from the baseline is recommended. For the primary prevention of CVD in patients with T2DM with a duration of diabetes ≥10 years, major cardiovascular risk factors, or target organ damage, an LDL-C goal of <70 mg/dL is recommended. In patients with T2DM with a duration of diabetes <10 years and no major cardiovascular risk factors, an LDL-C goal of <100 mg/dL is recommended.

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Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk

Cited by 343 publications

References 25 publications

Patient Selection for Pemafibrate Therapy to Prevent Adverse Cardiovascular Events

Patient Selection for Pemafibrate Therapy to Prevent Adverse Cardiovascular Events

The effects of pemafibrate and omega-3 fatty acid ethyl on apoB-48 in dyslipidemic patients treated with statin: A prospective, multicenter, open-label, randomized, parallel group trial in Japan (PROUD48 study)

Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement

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