Summer 2020 (Volume 30, Number 2)
HCQ and the Heart
By Zahi Touma, MD, PhD, FACP, FACR
Despite much in the media these days about antimalarials
(AM) for the treatment of COVID-19, hydroxychloroquine
(HCQ) and chloroquine have been used for a
long time for the treatment of different rheumatic diseases, and
HCQ remains the cornerstone of systemic lupus erythematosus
(SLE) therapy. HCQ is preferred because of the lower incidence
of adverse retinal effects. The evidence supporting HCQ use in
SLE is very compelling and based on a large body of evidence.
HCQ controls SLE disease activity and allows glucocorticoid
discontinuation, improves survival rates, reduces some traditional
cardiovascular risk factors, has antithrombotic effect, reduces
damage and risk of flares, and is safe during pregnancy.1
In rheumatoid arthritis (RA), HCQ is one of the commonly prescribed
traditional non-biologic disease-modifying antirheumatic
drugs, and triple therapy for RA includes HCQ.2,3
AM can cause serious toxicity and are stored long term
in different organs including skin, eyes, skeletal muscle, and
cardiac tissue. Retinal toxicity is the most discussed adverse
effect, but other adverse events can also occur – skin hyperpigmentation,
neuromyopathy and cardiotoxicity.
We have recently studied whether cumulative AM use is
associated with ECG abnormalities in 453 patients (SLE duration
at ECG 19.7 ± 10.4 years).1 Conduction abnormalities
(bundle-branch block, incomplete or complete AV block,
QTc-prolongation and consequent torsades de pointes)
were slightly more prevalent than ECG features suggestive
of structural abnormalities (concentric hypertrophy with biatrial
enlargement and biventricular hypertrophy), 16% vs.
13% respectively; 26% of patients had both abnormalities. In
this cohort, 56% had cumulative AM dose above the median
of 1207 grams at time of their ECG, with 44% at or below
the median. While a cumulative AM dose above the median
predicted structural ECG abnormalities in univariate analysis,
in multivariate analysis the increased risk (OR 1.82;
95% CI: 0.95–3.47) was not statistically significant. More
importantly, AM cumulative dose was protective for conduction
abnormalities (OR 0.42; 95% CI: 0.22– 0.77, p=0.006).
In the nested case-control analysis, the protective effect of
AM against conduction abnormalities was also demonstrated
(OR 0.36), and an AM dose higher than median was not
significantly associated with structural abnormalities.
Other studies found similar prevalence for conduction
abnormalities (17%) in SLE after a 10-year follow up.4 Others
confirmed that the prevalence of conduction abnormalities in
SLE is similar to the general population.5 We have also demonstrated
a low prevalence of prolonged QTc (3 patients; 0.7%)1
while others reported a higher prevalence (6.5%) and found
an association with anti-Ro/SSA antibodies.6
Cardiac AM adverse effects are potentially reversible
if detected early and withdrawal of AM is essential. While
ECG may be normal or nonspecific, it might allow for early
detection and promote further assessment. More specific
tests for heart muscle damage (troponin I) might also facilitate
screening for cardiotoxicity in patients with elevated
creatine kinase.7 Though cardiac MRI and PET scan can be
utilized in the assessment for AM cardiotoxicity, endomyocardial
biopsy remains the gold standard test.
Recognition of potential adverse effects and potential
risk factors (excessive daily dose by weight, duration of use,
cumulative dose, existing renal disease, increasing age, liver
disease and other genetic factors) for AM toxicity along
with appropriate screening is crucial. Lastly, we recognize
that more specific tests for AM cardiotoxicity are needed
for appropriate risk stratification.
The COVID-19 pandemic resulted in the unconventional
use of HCQ as a therapeutic option in combination with
azithromycin. Concerns raised by the media and Health
Canada about the potential serious side effects associated
with HCQ are based on the fear that some patients may
obtain HCQ to prevent or treat COVID-19. Side effects with
the unsupervised use of HCQ can occur, but rheumatologists
are familiar with this drug and the potential side effects.
Rheumatologists have used HCQ for decades without
major side effects – we weigh the risks and benefits and,
more importantly, we follow patients closely and monitor
for HCQ toxicities. This is crucial for the successful management
of patients with rheumatic diseases on HCQ.
Zahi Touma, MD, PhD, FACP, FACR
Assistant Professor of Medicine,
Division of Rheumatology
Faculty of Medicine
University of Toronto
Krembil Research Institute (Krembil)
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to anti-malarials in systemic lupus erythematosus. Clinical and experimental rheumatology 2018 Jul-Aug;
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1-26. PubMed PMID: 26545940.
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frequency and incidence in a group of 112 patients (author's transl) Les troubles de conduction au cours
du lupus erythemateux. Frequence et incidence dans une population de 112 patients]. Annales de medecine interne 1981; 132(4):234-40. PubMed PMID: 7305172.
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hydroxychloroquine for connective tissue diseases. Rheumatology (Oxford, England) 2007 May;46(5):808-10. PubMed PMID: 17202178.
6. Bourre-Tessier J, Clarke AE, Huynh T, Bernatsky S, Joseph L, Belisle P, et al. Prolonged corrected QT interval in anti-Ro/SSA-positive adults with systemic lupus erythematosus. Arthritis Care Res (Hoboken) 2011
Jul; 63(7):1031-7. PubMed PMID: 21452253.
7. Tselios K, Gladman DD, Harvey P, Akhtari S, Su J, Urowitz MB. Abnormal Cardiac Biomarkers in Patients
with Systemic Lupus Erythematosus and No Prior Heart Disease: A Consequence of Antimalarials? J Rheumatol 2019 Jan; 46(1):64-9. PubMed PMID: 30068764.