Cardiac Complications Attributed to Chloroquine and Hydroxychloroquine: A Systematic Review of the Literature

Abstract

Introduction

Chloroquine and hydroxychloroquine are widely used in the long-term treatment of connective tissue disease and usually considered safe. However, chloroquine- or hydroxychloroquine-related cardiac disorder is a rare but severe adverse event, which can lead to death. This systematic review investigates cardiac complications attributed to chloroquine and hydroxychloroquine.

Methods

PubMED, EMBASE, and Cochrane database searches were conducted using keywords derived from MeSH terms. Reports published prior to 31 July, 2017 were eligible for inclusion, without restriction to study design. Searches were also conducted on reference lists of included studies.

Results

Eighty-six articles were identified, reporting individual cases or short series, providing information on 127 patients (65.4% female). A majority of patients were treated with chloroquine (58.3%), with the remaining treated with hydroxychloroquine (39.4%), or both in succession. Most patients had been treated for a long time (median 7 years, minimum 3 days; maximum 35 years) and with a high cumulative dose (median 1235 g for hydroxychloroquine and 803 g for chloroquine). Conduction disorders were the main side effect reported, affecting 85% of patients. Other non-specific adverse cardiac events included ventricular hypertrophy (22%), hypokinesia (9.4%), heart failure (26.8%), pulmonary arterial hypertension (3.9%), and valvular dysfunction (7.1%). For 78 patients reported to have been withdrawn from treatment, some recovered normal heart function (44.9%), while for others progression was unfavorable, resulting in irreversible damage (12.9%) or death (30.8%).

Limitations

The risk of cardiac complications attributed to chloroquine/hydroxychloroquine was not quantified because of the lack of randomized controlled trials and observational studies investigating the association.

Conclusions

Clinicians should be warned that chloroquine- or hydroxychloroquine-related cardiac manifestations, even conduction disorders without repercussion, may be initial manifestations of toxicity, and are potentially irreversible. Therefore, treatment withdrawal is required when cardiac manifestations are present.

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Authors

Contributions

CC and YMP collected the data and analyzed and interpreted the patient data regarding the cardiac complications of chloroquine/hydroxychloroquine. CC and YMP wrote a draft of the manuscript. FR, HV, and CJ provided expertise in heart disease and imaging modalities and participated in writing the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yves-Marie Pers.

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No sources of funding were used to assist in the preparation of this study.

Conflict of interest

Clotilde Chatre, François Roubille, Hélène Vernhet, Christian Jorgensen, and Yves-Marie Pers have no conflicts of interest that are directly relevant to the content of this study.

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Chatre, C., Roubille, F., Vernhet, H. et al. Cardiac Complications Attributed to Chloroquine and Hydroxychloroquine: A Systematic Review of the Literature. Drug Saf 41, 919–931 (2018). https://doi.org/10.1007/s40264-018-0689-4

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