Turn the Beat Around: An Encore Performance or One Last Dance for Hydroxychloroquine?

^{By Douglas L. Jennings, PharmD, FACC, FAHA, FCCP, FHFSA, BCPS}

Just when it seemed that hydroxychloroquine had officially been relegated to the COVID-19 drug therapy graveyard: a new study emerges. This time from my old haunt, Henry Ford Hospital in Detroit Michigan.

The journey has certainly been a rocky one for this antiquated drug therapy. Riding on the waves of small preliminary studies, this inexpensive and widely-available medication garnered support from the highest levels of the US government earlier this spring. Then followed a wave of negative studies—including one from my new haunt (New York)—along with other massive studies from the NIH and the RECOVERY network in the U.K., hydroxychloroquine quickly fell out of favor. The Oxford dataset was particularly massive: a total of 1,542 patients were randomized to hydroxychloroquine and compared with 3,132 patients randomized to usual care alone. There was no significant difference in the primary endpoint of 28-day mortality (25.7% hydroxychloroquine vs. 23.5% usual care; hazard ratio 1.11 [95% confidence interval 0.98-1.26]; p=0.10). There was also no evidence of beneficial effects on hospital stay duration or other outcomes. 

This new observation study examined outcomes of patients admitted for COVID-19 disease and evaluated mortality rates according to a recipe of several drug therapies. Overall crude mortality rates were 18.1% in the entire cohort, 13.5% in the hydroxychloroquine alone group, 20.1% among those receiving hydroxychloroquine plus azithromycin, 22.4% among the azithromycin alone group, and 26.4% for neither drug. The authors cite the early initiation—91% of patients were treated within 48 hours—as the possible source of these beneficial outcomes.

Several important caveats for this new paper:

• The New York data also started most patients within the first day and found no benefit of this therapy
• Nearly twice as many patients in the Henry Ford paper who received hydroxychloroquine were taking steroids, which is relevant as dexamethasone recently showed significant promise in reducing mortality rates for patients with severe COVID-19 disease
• The Henry Ford study excluded nearly 10% of their patients who had not yet been discharged from the hospital, which may have skewed the results in favor of hydroxychoroquine

Having reviewed this new paper and evaluated the available literature, I think that the preponderance of the evidence still suggests that hydroxychloroquine is not effective for treating Covid-19 disease. Based on the lack of efficacy, combined with the potential cardiotoxicity, clinicians should not prescribe or recommend hydroxychloroquine for COVID-19 disease until additional data is available.

Dr Jennings is currently an Associate Professor of Pharmacy at Long Island University and the clinical pharmacist for the Heart Transplant and LVAD teams at NewYork- Presbyterian Hospital Columbia University Irving Medical Center.  He is an active researcher in his field, and he has published over 120 peer-reviewed abstracts and manuscripts, primarily focusing on the pharmacotherapy of patients under mechanical circulatory support. As a recognized expert in this area, he has been invited to speak at numerous national and international venues, including meetings in France, Saudia Arabia, India. Finally, Dr. Jennings has been active in professional organizations throughout his career. He is a fellow of the American College of Clinical Pharmacy, the American College of Cardiology, the Heart Failure Society of America, and the American Heart Association. 

References:

Recovery. No clinical benefit from use of hydroxychloroquine in hospitalised patients with COVID-19. https://www.recoverytrial.net/news/statement-from-the-chief-investigators-of-the-randomised-evaluation-of-covid-19-therapy-recovery-trial-on-hydroxychloroquine-5-june-2020-no-clinical-benefit-from-use-of-hydroxychloroquine-in-hospitalised-patients-with-covid-19. Published June 2020.

CNN. Commonly used steroid reduces risk of death in sickest coronavirus patients, preliminary study results suggest. https://www.cnn.com/2020/06/16/health/dexamethasone-covid-drug-recovery-trial-bn/index.html. June 16, 2020.

Arshad S, Kilgore P, Chaudhry ZS, et al. Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19 [published online ahead of print, 2020 Jul 2]. Int J Infect Dis. 2020;97:396-403. doi:10.1016/j.ijid.2020.06.099