Long-Term Use of Hydroxychloroquine May Increase Mortality Risk

Risk of hydroxychloroquine cardiovascular disease

A retrospective study published in The Lancet Rheumatology shows that the long-term use of hydroxychloroquine to treat rheumatoid arthritis patients may increase the risk of cardiovascular mortality.

Furthermore, wrote authors, who were led by Patrick Ryan, Ph.D., of Columbia University Irving Medical Center and the pharmaceutical company, Janssen Research and Development, adding azithromycin can worsen outcomes.

“The addition of azithromycin increases the risk of heart failure and cardiovascular mortality even in the short term. We call for careful consideration of the benefit–risk trade-off when counselling those on hydroxychloroquine treatment,” the authors wrote.

The recommendation is based on the outcomes of a multinational, retrospective study, new user cohort studies of adult rheumatoid arthritis patients. The study included 956,374 patients who u sed hydroxychloroquine, 310,350 who used sulfasalazine, and, 323,122 who used hydroxychloroquine with azithromycin, and, 351,956 who used hydroxychloroquine and amoxicillin.

No other excess risk of severe adverse events was identified at 30 days in either the hydroxychloroquine treatment group or the sulfasalazine treatment group. But in the long term, hydroxychloroquine use appeared to be associated with increased cardiovascular mortality (calibrated HR 1·65 [95% CI 1·12–2·44]). And, adding azithromycin to the treatment appeared to be associated with an increased risk of 30-day cardiovascular mortality (calibrated HR 2·19 [95% CI 1·22–3·95]), chest pain or angina (1·15 [1·05–1·26]), and heart failure (1·22 [1·02–1·45]).

The study is based on the analysis of 14 sources of claims data or electronic medical records from Germany, Japan, the Netherlands, Spain, the United Kingdom and the United States.

“Our results suggest that long-term use of hydroxychloroquine leads to increased cardiovascular mortality, which might relate to cumulative effects of hydroxychloroquine leading to an increased risk of QT (interval) lengthening and potentially to sudden undetected torsade-de-pointes and cardiovascular death. Although long-term treatment with hydroxychloroquine is not expected for the management of COVID-19, some research suggests that the higher doses prescribed for COVID-19 than for rheumatoid arthritis can, even in the short term, lead to equivalent side-effects given the long half-life of hydroxychloroquine,” the authors wrote.

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REFERENCE

Jennifer C E Lane, MRCS, James Weaver, MSc, Kristin Kostka, MPH, Talita Duarte-Salles, PhD, et al. "Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study," The Lancet Rheumatology. Online First Aug. 21, 2020.