Rationale and design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study

Aruna D. Pradhan, Nina P. Paynter, Brendan M. Everett, Robert J. Glynn, Pierre Amarenco, Marshall Elam, Henry Ginsberg, William R. Hiatt, Shun Ishibashi, Wolfgang Koenig, Børge G. Nordestgaard, Jean Charles Fruchart, Peter Libby, Paul M. Ridker

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Abstract

Observational, genetic, and experimental data indicate that triglyceride rich lipoproteins (TRLs) likely participate causally in atherothrombosis. Yet, robust clinical trial evidence that triglyceride (TG) lowering therapy reduces cardiovascular events remains elusive. The selective peroxisome proliferator-activated receptor alpha modulator (SPPARM-α), pemafibrate, will be used to target residual cardiovascular risk remaining after treatment to reduce low-density lipoprotein cholesterol (LDL-C) in individuals with the dyslipidemia of type 2 diabetes mellitus (T2). The PROMINENT study will randomly allocate approximately 10,000 participants with T2D, mild-to-moderate hypertriglyceridemia (TG: 200– 499 mg/dl; 2.26– 5.64 mmol/l) and low high-density lipoprotein cholesterol levels (HDL-C: ≤40 mg/dl; 1.03 mmol/l) to either pemafibrate (0.2 mg twice daily) or matching placebo with an average expected follow-up period of 3.75 years (total treatment phase 5 years; 24 countries). At study entry, participants must be receiving either moderate-to-high intensity statin therapy or meet specified LDL-C criteria. The study population will be one-third primary and two-thirds secondary prevention (established cardiovascular disease). The primary endpoint is a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, hospitalization for unstable angina requiring urgent coronary revascularization, and cardiovascular death. This event-driven study will complete when 1092 adjudicated primary endpoints have accrued with at least 200 occurring in women. Statistical power is at least 90% to detect an 18% reduction in the primary endpoint. Pre-specified secondary and tertiary endpoints include all-cause mortality, hospitalization for heart failure, new or worsening peripheral artery disease, new or worsening diabetic retinopathy and nephropathy, and change in biomarkers including select lipid and non-lipid biomarkers, inflammatory and glycemic parameters.

Original languageEnglish (US)
Pages (from-to)80-93
Number of pages14
JournalAmerican Heart Journal
Volume206
DOIs
StatePublished - Dec 1 2018

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Triglycerides
LDL Cholesterol
Hospitalization
Biomarkers
Hydroxymethylglutaryl-CoA Reductase Inhibitors
PPAR alpha
Hypertriglyceridemia
Peripheral Arterial Disease
Unstable Angina
Diabetic Nephropathies
Diabetic Retinopathy
Therapeutics
Dyslipidemias
Secondary Prevention
Type 2 Diabetes Mellitus
HDL Cholesterol
Lipoproteins
Cardiovascular Diseases
Heart Failure
Stroke

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Rationale and design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study. / Pradhan, Aruna D.; Paynter, Nina P.; Everett, Brendan M.; Glynn, Robert J.; Amarenco, Pierre; Elam, Marshall; Ginsberg, Henry; Hiatt, William R.; Ishibashi, Shun; Koenig, Wolfgang; Nordestgaard, Børge G.; Fruchart, Jean Charles; Libby, Peter; Ridker, Paul M.

In: American Heart Journal, Vol. 206, 01.12.2018, p. 80-93.

Research output: Contribution to journalArticle

Pradhan, AD, Paynter, NP, Everett, BM, Glynn, RJ, Amarenco, P, Elam, M, Ginsberg, H, Hiatt, WR, Ishibashi, S, Koenig, W, Nordestgaard, BG, Fruchart, JC, Libby, P & Ridker, PM 2018, 'Rationale and design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study', American Heart Journal, vol. 206, pp. 80-93. https://doi.org/10.1016/j.ahj.2018.09.011
Pradhan, Aruna D. ; Paynter, Nina P. ; Everett, Brendan M. ; Glynn, Robert J. ; Amarenco, Pierre ; Elam, Marshall ; Ginsberg, Henry ; Hiatt, William R. ; Ishibashi, Shun ; Koenig, Wolfgang ; Nordestgaard, Børge G. ; Fruchart, Jean Charles ; Libby, Peter ; Ridker, Paul M. / Rationale and design of the Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients with Diabetes (PROMINENT) study. In: American Heart Journal. 2018 ; Vol. 206. pp. 80-93.
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