American College of Rheumatology White Paper on Antimalarial Cardiac Toxicity

Abstract

Hydroxychloroquine (HCQ) and chloroquine (CQ) are well-established medications used in treating systemic lupus erythematosus and rheumatoid arthritis, as well as skin conditions such as cutaneous lupus erythematosus. In rare cases, arrhythmias and conduction system abnormalities, as well as cardiomyopathy, have been reported in association with HCQ/CQ use. Recently, however, the corrected QT interval (QTc)-prolonging potential of these medications, and risk of torsade de pointes (TdP) in particular, have been highlighted in the setting of their experimental use for COVID-19 infection. This report was undertaken to summarize the current understanding of HCQ/CQ cardiac toxicity, describe QTc prolongation and TdP risks, and discuss areas of priority for future research. A working group of experts across rheumatology, cardiology, and dermatology performed a nonsystematic literature review and offered a consensus-based expert opinion. Current data clearly indicate that HCQ and CQ are invaluable medications in the management of rheumatic and dermatologic diseases, but they are associated with QTc prolongation by directly affecting cardiac repolarization. Prescribing clinicians should be cognizant of this small effect, especially in patients taking additional medications that prolong the QTc interval. Long-term use of HCQ/CQ may lead to a cardiomyopathy associated with arrhythmias and heart failure. Risk and benefit assessment should be considered prior to initiation of any medication, and both initial and ongoing risk-benefit assessments are important with regard to prescription of HCQ/CQ. While cardiac toxicity related to HCQ/CQ treatment of rheumatic diseases is rarely reported, it can be fatal. Awareness of the potential adverse cardiac effects of HCQ and CQ can increase the safe use of these medications. There is a clear need for additional research to allow better understanding of the cardiovascular risk and safety profile of these therapies used in the management of rheumatic and cutaneous diseases.

Hydroxychloroquine lowers Alzheimer’s disease and related dementias risk and rescues molecular phenotypes related to Alzheimer’s disease

“…The doses tested in our in vitro experiments (i.e., 25 µM and 50 µM) may be consistent with brain concentrations achievable with conventional dosing of HCQ in RA patients. Furthermore, HCQ has a well-established safety profile with serious side effects being relatively rare [62], although additional screening for cardiac arrhythmias in some patients may be necessary [63,64].…”

Prevalence of ECG testing and characteristics among new hydroxychloroquine and chloroquine users within a multi-center tertiary care center

“…In our study, age and prior MI were independently associated with prolonged QTc at follow-up among females and prior MI was the only predictor of prolonged QTc at follow-up among males. Indeed, a recent white paper conducted by a working group of experts spanning different subspecialties, suggested that clinicians should be aware of the potential risk of cardiotoxicity of HCQ/CQ and consider a risk and benefit assessment prior to initiation of these medications [ 15 ]. Many studies examining the risk of arrhythmia with HCQ use among SLE and RA patients, several sparked by the COVID-19 pandemic [ 16 – 20 ], are still in abstract form, limited to retrospective analysis, using electronic medical records, and/or based on small cohorts [ 21 ].…”

“…We also acknowledge that although HCQ has a prolonged half-life of 40–50 days, the effect of HCQ/CQ on QTc may happen as early as 2 days after starting the medications and that even among similar dosing in mg/kg/day, there is variability in HCQ blood levels [ 22 – 24 ]. We used the 2-month waiting period as recommended by the white paper on HCQ antimalarial HCQ/CQ toxicity [ 15 ]. Therefore, by including the 2-month after HCQ/CQ initiation period as part of the baseline period, there may have been some patients who developed prolonged QTc during the baseline period.…”

Diagnosis and Management of Cutaneous Manifestations of Autoimmune Connective Tissue Diseases

“… 46 Electrocardiogram at baseline and shortly after initiation of hydroxychloroquine can also be considered, particularly in those taking other QTc prolonging medications. 47 …”

“…Electrocardiogram at baseline and shortly after initiation of hydroxychloroquine can also be considered, particularly in those taking other QTc prolonging medications. 47 Systemic corticosteroids should not be used as a long-term immunomodulatory agent in patients with cutaneous lupus. However, short-term use, in conjunction with steroid sparing agents, can be considered for patients with severe, rapidly progressive, or refractory disease (ie, patients with rapidly progressive discoid lupus at high risk of permanent scarring and dyspigmentation).…”