Hydroxychloroquine and chloroquine (HCQ/CQ) were early treatments for COVID-19, until trials of HCQ were halted because of concerns about arrhythmias. Other known cardiovascular adverse effects of HCQ/CQ are cardiomyopathy and conduction system abnormalities, including prolonged QTc interval.
Yet in a large retrospective study published in Rheumatology International, researchers at Brigham and Women’s Hospital found that before the COVID-19 pandemic, electrocardiograms (ECGs) were infrequently obtained before initiation of HCQ/CQ and even less often during follow-up. Lack of testing was particularly pronounced among women, a population more likely to use HCQ/CQ as they are disproportionately affected by rheumatic diseases.
Authors included May Y. Choi, MD, formerly a fellow in the Division of Rheumatology, Inflammation and Immunity, Brittany Weber, MD, PhD, director of the Cardio-Rheumatology Clinic, Karen H. Costenbader, MD, MPH, director of the Lupus Program, and colleagues.
The researchers analyzed records on 10,248 adult patients at Mass General Brigham and two partner community hospitals who received a new prescription for HCQ/CQ between January 1, 2015, and March 1, 2020 (before the pandemic). The two most common indications were rheumatoid arthritis (29% of patients) and systemic lupus erythematosus (14%). Nearly all patients (99.7%) were prescribed HCQ.
12-lead resting ECGs, where available, were reviewed for the baseline period and follow-up period (defined as 10 months after the first prescription of HCQ/CQ). Abnormally prolonged QTc interval was defined as >470 ms for women and >450 ms for men.
Frequency of ECG
The frequency of ECG before and after HCQ/CQ prescription was low:
- All new users—24% had a baseline ECG, 15% had a follow-up ECG and 8% had both
- Female new users—22%, 14%, and 8%
- Male new users—30%, 18%, and 11%
Frequency of Prolonged QTc
Among patients who had both baseline and follow-up ECGs:
- 13% of 634 women and 12% of 210 men had normal QTc at baseline but developed prolonged QTc during follow-up (statistically similar)
- 190 women with prolonged QTc at baseline—60% continued to have prolonged QTc throughout follow-up
- 103 men with prolonged QTc at baseline—77% continued to have prolonged QTc throughout follow-up
Predictors of Prolonged QTc
In the adjusted logistic regression model:
- For women—Older age at initiation of HCQ/CQ (OR, 1.01; 95% CI, 1.00–1.02) and prior myocardial infarction (MI) (OR, 2.52; 95% CI, 1.69–3.76) were significantly associated with prolonged QTc during follow-up
- For men—Prior MI (OR, 1.97; 95% CI, 1.10–3.52) was the only significant predictor
The other factors studied were race/ethnicity, body mass index, history of stroke, history of hypothyroidism, and disease indication for HCQ/CQ.
Paradigm Change Needed?
Rheumatologists and dermatologists have prescribed HCQ/CQ for decades with no obvious cardiac safety signal. However, the true risk isn’t known since cardiac monitoring hasn’t been performed routinely and most cases of prolonged QTc are asymptomatic. Prospective studies are needed to ascertain that risk.
In the meantime, a white paper developed by a multidisciplinary working group for the American College of Rheumatology advises clinicians to remain aware of the potential cardiotoxicity of HCQ/CQ and conduct a risk/benefit assessment before prescribing these drugs.