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List of authors.- Aruna Das Pradhan, M.D., M.P.H.,
- Robert J. Glynn, Sc.D.,
- Jean-Charles Fruchart, Ph.D.,
- Jean G. MacFadyen, B.A.,
- Elaine S. Zaharris, B.A.,
- Brendan M. Everett, M.D., M.P.H.,
- Stuart E. Campbell, B.A.,
- Ryu Oshima, M.S., R.Ph.,
- Pierre Amarenco, M.D.,
- Dirk J. Blom, M.D., Ph.D.,
- Eliot A. Brinton, M.D.,
- Robert H. Eckel, M.D.,
- Marshall B. Elam, M.D., Ph.D.,
- João S. Felicio, M.D., Ph.D.,
- Henry N. Ginsberg, M.D.,
- Assen Goudev, M.D.,
- Shun Ishibashi, M.D., Ph.D.,
- Jacob Joseph, M.D.,
- Tatsuhiko Kodama, M.D., Ph.D.,
- Wolfgang Koenig, M.D.,
- Lawrence A. Leiter, M.D.,
- Alberto J. Lorenzatti, M.D.,
- Boris Mankovsky, M.D.,
- Nikolaus Marx, M.D.,
- Børge G. Nordestgaard, M.D., D.M.S.C.,
- Dénes Páll, M.D.,
- Kausik K. Ray, M.D.,
- Raul D. Santos, M.D., Ph.D.,
- Handrean Soran, M.D.,
- Andrey Susekov, M.D., Ph.D., D.Sc.,
- Michal Tendera, M.D.,
- Koutaro Yokote, M.D., Ph.D.,
- Nina P. Paynter, Ph.D.,
- Julie E. Buring, Sc.D.,
- Peter Libby, M.D.,
- and Paul M Ridker, M.D., M.P.H.
- for the PROMINENT Investigators*
Abstract
Background
High triglyceride levels are associated with accrued cardiovascular risk, but whether reductions successful these levels would little the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator–activated receptor α modulator, reduces triglyceride levels and improves different lipid levels.
Methods
In a multinational, double-blind, randomized, controlled trial, we assigned patients with benignant 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterin levels of 40 mg per deciliter oregon little to person pemafibrate (0.2-mg tablets doubly daily) oregon matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy oregon could not person statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterin levels of 100 mg per deciliter oregon lower. The superior efficacy extremity constituent was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, oregon decease from cardiovascular causes.
Results
Among 10,497 patients (66.9% with erstwhile cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterin level 33 mg per deciliter, and LDL cholesterin level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate connected lipid levels astatine 4 months were −26.2% for triglycerides, −25.8% for very-low-density lipoprotein (VLDL) cholesterol, −25.6% for remnant cholesterin (cholesterol transported successful triglyceride-rich lipoproteins aft lipolysis and lipoprotein remodeling), −27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A superior end-point lawsuit occurred successful 572 patients successful the pemafibrate radical and successful 560 of those successful the placebo radical (hazard ratio, 1.03; 95% assurance interval, 0.91 to 1.15), with nary evident effect modification successful immoderate prespecified subgroup. The wide incidence of superior adverse events did not disagree importantly betwixt the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a little incidence of nonalcoholic fatty liver disease.
Conclusions
Among patients with benignant 2 diabetes, mild-to-moderate hypertriglyceridemia, and debased HDL and LDL cholesterin levels, the incidence of cardiovascular events was not little among those who received pemafibrate than among those who received placebo, though pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.)
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Sign InFunding and Disclosures
Supported by Kowa Research Institute done an instauration assistance to the Center for Cardiovascular Disease Prevention astatine Brigham and Women’s Hospital.
Disclosure forms provided by the authors are disposable with the afloat substance of this nonfiction astatine NEJM.org.
This nonfiction was published connected November 5, 2022, astatine NEJM.org.
A data sharing statement provided by the authors is disposable with the afloat substance of this nonfiction astatine NEJM.org.
Author Affiliations
From the Center for Cardiovascular Disease Prevention, Division of Preventive Medicine (A.D.P., R.J.G., J.G.M., E.S.Z., B.M.E., N.P.P., J.E.B., P.M.R) and the Division of Cardiovascular Medicine (B.M.E.,P.L., P.M.R.), Brigham and Women’s Hospital, the Division of Cardiovascular Medicine, Veteran Affairs Boston Health Care System (A.D.P., J.J.), and Kowa Pharma Development (R.O.) — each successful Boston; University of Lille, Lille (J.-C.F.) and the Department of Neurology and Stroke Center, Paris Cité University, Paris (P.A.) — some successful France; Kowa Research Institute, Morrisville, NC (S.E.C.); the Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa (D.J.B.); Utah Lipid Center, Salt Lake City (E.A.B.); the University of Colorado School of Medicine, Aurora (R.H.E.); the University of Tennessee Health Science Center, Memphis (M.B.E.); the Division of Endocrinology, Universitário Hospital João de Barros Barreto, Belém (J.S.F.), and the Heart Institute (InCor), University of São Paulo Medical School Hospital, and Hospital Israelita Albert Einstein (R.D.S.), São Paulo — each successful Brazil; Columbia University Vagelos College of Physicians and Surgeons, New York (H.N.G.); Queen Giovanna University Hospital, Sofia, Bulgaria (A.G.); Jichi Medical University, Shimotsuke (S.I.), the Research Center for Advanced Science and Technology, University of Tokyo, Tokyo (T.K.), and Chiba University Graduate School of Medicine, Chiba (K.Y.) — each successful Japan; Deutsches Herzzentrum München, Technische Universität München and German Center for Cardiovascular Research, Partner Site Munich Heart Alliance, Munich (W.K.), Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm (W.K.), and Rheinisch–Westfälische Technische Hochschule Aachen, University Hospital Aachen, Aachen (N.M.) — each successful Germany; McMaster University and Population Health Research Institute, Hamilton, ON (P.A.) and the Division of Endocrinology and Metabolism, St. Michael’s Hospital, University of Toronto, Toronto (L.A.L.) — some successful Canada; Docencia, Asistencia Médica e Investigación Clínica Medical Institute–Rusculleda Foundation for Research, Córdoba, Argentina (A.J.L.); Shupyk National Healthcare University of Ukraine, Kyiv (B.M.); Copenhagen University Hospital–Herlev Gentofte, University of Copenhagen, Copenhagen (B.G.N.); the Department of Medical Clinical Pharmacology, University of Debrecen, Debrecen, Hungary (D.P.); the Department of Primary Care and Public Health, Imperial College London, London (K.K.R.), and the Department of Endocrinology, Diabetes, and Metabolism, Manchester University Hospital NHS Foundation Trust, Manchester (H.S.) — some successful the United Kingdom; the Russian Academy of Postgraduate Medical Education, Moscow (A.S.); and the Department of Cardiology and Structural Heart Diseases, Medical University of Silesia, Katowice, Poland (M.T.).
Dr. Das Pradhan tin beryllium contacted astatine [email protected] and Dr. Ridker tin beryllium contacted astatine [email protected] oregon astatine the Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Ave., Boston, MA 02215.
A implicit database of the PROMINENT investigators is provided successful the Supplementary Appendix, disposable astatine NEJM.org.
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