Clinical studies of cholesterol-modifying drugs for preventing or treating COVID-19.

Key Messages

This is a summary of ongoing clinical trials testing the use of cholesterol modifying drugs for treating COVID-19.

A search identified 40 different trials testing the effect of cholesterol modifying drugs for managing or preventing COVID-19, three of which are investigating fenofibrate.

Fenofibrate is the only fibrate being investigated out of the 40 different trials. In the three ongoing fenofibrate trials, the use of fenofibrate vs a placebo in hospitalized, non-ICU patients with COVID-19 is compared.

Fibrates may decrease SARS-CoV-2 infectivity by blocking viral entry into cells. This could occur via increased sulfatide levels and by destabilization of a region of the SARS-CoV-2 spike protein to prevent it binding to ACE2, the cell surface protein the virus uses to enter the cell.

The strengths and usefulness of the ongoing fibrate trials are due to the disease outcomes being studied. The studies monitor patient survival, the level of acute respiratory distress, blood markers indicating inflammation levels, and the need for mechanical ventilation.

medRxiv

Publication Date: May 5, 2021
Peer Reviewed: No
Publication Type: Review/Commentary/Letter
DOI: https://www.doi.org/10.1101/2021.05.03.21256468

Lipid-Modulating Agents for Prevention or Treatment of COVID-19 in Randomized Trials

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 YH Lip, Gregg W. Stone, Harlan M. Krumholz, Peter Libby, Samuel Z. Goldhaber, Behnood Bikdeli

Abstract

Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation, endothelial activation, and multi-organ manifestations. Lipid modulating agents may be useful in treating patients with COVID-19. They 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 triglycerides portends worse outcome in patients with COVID-19. Upon a systematic search, 40 RCTs with lipid modulating agents were identified, including 17 statin trials, 14 omega-3 fatty acids RCTs, 3 fibrates RCTs, 5 niacin RCTs, and 1 dalcetrapib RCT for management or prevention of COVID-19. This manuscript summarizes the ongoing or completed randomized controlled trials (RCTs) of lipid modulating agents in COVID-19 and the implications of these trials for patient management.