Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19: JACC State-of-the-Art Review

Azita H Talasaz; Parham Sadeghipour; Maryam Aghakouchakzadeh; Isaac Dreyfus; Hessam Kakavand; Hamid Ariannejad; Aakriti Gupta; Mahesh V Madhavan; Benjamin W Van Tassell; David Jimenez; Manuel Monreal; Muthiah Vaduganathan; John Fanikos; Dave L Dixon; Gregory Piazza; Sahil A Parikh; Deepak L Bhatt; Gregory Y H Lip; Gregg W Stone; Harlan M Krumholz; Peter Libby; Samuel Z Goldhaber; Behnood Bikdeli

doi:10.1016/j.jacc.2021.08.021

Investigating Lipid-Modulating Agents for Prevention or Treatment of COVID-19: JACC State-of-the-Art Review

J Am Coll Cardiol. 2021 Oct 19;78(16):1635-1654. doi: 10.1016/j.jacc.2021.08.021.

Authors

Azita H Talasaz¹, Parham Sadeghipour², Maryam Aghakouchakzadeh³, Isaac Dreyfus⁴, Hessam Kakavand³, Hamid Ariannejad⁵, Aakriti Gupta⁶, Mahesh V Madhavan⁷, Benjamin W Van Tassell⁸, David Jimenez⁹, Manuel Monreal¹⁰, Muthiah Vaduganathan¹¹, John Fanikos¹², Dave L Dixon⁸, Gregory Piazza¹¹, Sahil A Parikh⁷, Deepak L Bhatt¹¹, Gregory Y H Lip¹³, Gregg W Stone¹⁴, Harlan M Krumholz¹⁵, Peter Libby¹¹, Samuel Z Goldhaber¹¹, Behnood Bikdeli¹⁶

Affiliations

¹ Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacotherapy and Outcome Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA.
² Cardiovascular Intervention Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.
³ Department of Clinical Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
⁴ NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA.
⁵ Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.
⁶ NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA; Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, USA; Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, Connecticut, USA.
⁷ NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, New York, USA; Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, USA.
⁸ Department of Pharmacotherapy and Outcome Science, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA; Pauley Heart Center, Division of Cardiology, Department of Internal Medicine, School of Pharmacy, Virginia Commonwealth University, Richmond, Virginia, USA.
⁹ Respiratory Department, Hospital Ramón y Cajal and Medicine Department, Universidad de Alcalá (Instituto de Ramón y Cajal de Investigación Sanitaria), Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, Madrid, Spain.
¹⁰ Department of Internal Medicine, Hospital Universitari Germans Trials i Pujol, Universidad Católica San Antonio de Murcia, Barcelona, Spain.
¹¹ Division of Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹² Department of Pharmacy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
¹³ Liverpool Centre for Cardiovascular Science, Liverpool Heart and Chest Hospital, University of Liverpool, Liverpool, United Kingdom; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
¹⁴ Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, USA; Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁵ Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, Connecticut, USA; Department of Health Policy and Administration, Yale School of Public Health, New Haven, Connecticut, USA; Section of Cardiovascular Medicine, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
¹⁶ Clinical Trials Center, Cardiovascular Research Foundation, New York, New York, USA; Center for Outcomes Research and Evaluation (CORE), Yale School of Medicine, New Haven, Connecticut, USA; Division of Cardiovascular Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. Electronic address: bbikdeli@bwh.harvard.edu.

Abstract

Coronavirus disease-2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multiorgan manifestations. Lipid-modulating agents may be useful in treating patients with COVID-19. These agents may inhibit viral entry by lipid raft disruption or ameliorate the inflammatory response and endothelial activation. In addition, dyslipidemia with lower high-density lipoprotein cholesterol and higher triglyceride levels portend worse outcomes in patients with COVID-19. Upon a systematic search, 40 randomized controlled trials (RCTs) with lipid-modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrate RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for the management or prevention of COVID-19. From these 40 RCTs, only 2 have reported preliminary results, and most others are ongoing. This paper summarizes the ongoing or completed RCTs of lipid-modulating agents in COVID-19 and the implications of these trials for patient management.

Keywords: COVID-19; fibrate; lipid-modulating agent; niacin; omega-3; statin.

Publication types

Research Support, N.I.H., Extramural
Review

MeSH terms

Amides / pharmacology
Amides / therapeutic use
COVID-19 / prevention & control*
COVID-19 Drug Treatment*
Esters / pharmacology
Esters / therapeutic use
Fatty Acids, Omega-3 / pharmacology
Fatty Acids, Omega-3 / therapeutic use*
Fibric Acids / pharmacology
Fibric Acids / therapeutic use*
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Lipid Regulating Agents / pharmacology
Lipid Regulating Agents / therapeutic use
Niacin / pharmacology
Niacin / therapeutic use*
Randomized Controlled Trials as Topic
Sulfhydryl Compounds / pharmacology
Sulfhydryl Compounds / therapeutic use

Substances

Amides
Esters
Fatty Acids, Omega-3
Fibric Acids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipid Regulating Agents
Sulfhydryl Compounds
Niacin
dalcetrapib

Abstract

Publication types

MeSH terms

Substances

Grants and funding