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. 2021;17(3):319-327.
doi: 10.2174/1573403X16666201014144022.

Cardiac Complications Attributed to Hydroxychloroquine: A Systematic Review of the Literature Pre-COVID-19

Georgi Fram  1 , Dee D Wang  1 , Kelly Malette  1 , Pedro Villablanca  1 , Guson Kang  1 , Kent So  1 , Mir B Basir  1 , Arfaat Khan  2 , John E McKinnon  3 , Marcus Zervos  3 , William W O'Neill  1
Affiliations

Cardiac Complications Attributed to Hydroxychloroquine: A Systematic Review of the Literature Pre-COVID-19

Georgi Fram et al. Curr Cardiol Rev. 2021.

Abstract

Introduction: Hydroxychloroquine has been used for rheumatological diseases for many decades and is considered a safe medication. With the COVID-19 outbreak, there has been an increase in reports associating cardiotoxicity with hydroxychloroquine. It is unclear if the cardiotoxic profile of hydroxychloroquine is previously underreported in the literature or is it a manifestation of COVID-19 and therapeutic interventions. This manuscript evaluates the incidence of cardiotoxicity associated with hydroxychloroquine prior to the onset of COVID-19.

Methods: PubMED, EMBASE, and Cochrane databases were searched for keywords derived from MeSH terms prior to April 9, 2020. Inclusion eligibility was based on appropriate reporting of cardiac conditions and study design.

Results: A total of 69 articles were identified (58 case reports, 11 case series). The majority (84%) of patients were female, with a median age of 49.2 (range 16-92) years. 15 of 185 patients with cardiotoxic events were in the setting of acute intentional overdose. In acute overdose, the median ingestion was 17,857 ± 14,873 mg. 2 of 15 patients died after acute intoxication. In patients with long-term hydroxychloroquine use (10.5 ± 8.9 years), new onset systolic heart failure occurred in 54 of 155 patients (35%) with median cumulative ingestion of 1,493,800 ± 995,517 mg. The majority of patients improved with the withdrawal of hydroxychloroquine and standard therapy.

Conclusion: Millions of hydroxychloroquine doses are prescribed annually. Prior to the COVID-19 pandemic, cardiac complications attributed to hydroxychloroquine were uncommon. Further studies are needed to understand the impact of COVID-19 on the cardiovascular system to understand the presence or absence of potential medication interactions with hydroxychloroquine in this new pathophysiological state.

Keywords: COVID-19; Clinical cardiology; SLE.; cardiac complications; hydroxychloroquine; infectious disease.

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