Despite the widespread clinical use of hydroxychloroquine (HCQ) as a disease-modifying antirheumatic drug for long-term rheumatoid arthritis (RA) treatment, only a limited data set consisting of case reports and case series is available to confirm the risk of HCQ cardiotoxicity, a rare but potentially life-threatening side effect.1
Speaking during the clinical science abstract presentation for the e-congress of EULAR 2020, Dr. Ahmed A. Sorour, Division of Rheumatology at Mayo Clinic in Rochester, Minnesota, said, “Literature has argued over the cardioprotective and cardiotoxic role of HCQ. Heart failure (HF) is a rare adverse effect attributed to the drug, but these data are limited to case reports or series. Knowledge gaps exist on the risk of HF in RA patients using HCQ.”
A major hurdle in determining the risk of HF associated with HCQ treatment for RA patients is the lack of large cohort studies. To examine this relationship, Dr. Sorour and his colleagues from the Cardiovascular and Biostatistical Department conducted a nested case-control study among residents of Olmsted County, Minnesota from 1980 to 2013. The study consisted of 1,078 participants (≥18 years), of which 143 RA patients (mean age 65.8, 62% female) were diagnosed with HF as defined by the Framingham criteria, and were matched by age, sex and year of RA incidence to the corresponding control group consisting of 143 RA patients (mean age 64.5, 62% female) with no HF. Both groups are drawn from the same population with RA, meeting the 1987 American College of Radiology (ACR) criteria.2
According to the study, the proportion of patients positive for RA antibody have similar cyclic citrullinated peptide, rheumatoid factor, RA duration, body mass index, and smoking status. At the same time, hypertension and diabetes were more prevalent in the HF group.2 Moreover, 71 HF patient cases and 69 non-HF patient controls used HCQ before HF diagnosis or index date. The median (interquartile range) duration of HCQ use was 2.8 (0.6, 10.0) years for cases and 2.5 (0.7, 8.2) for controls.2
The median cumulative dose of HCQ was 371g and 302g in cases and controls, respectively. The findings revealed that 55% of cases and 54% of controls received a cumulative dose of ≥300g HCQ with no observed association with HF incidence (OR=0.92; 95% CI: 0.41-2.08). Likewise, HCQ cumulative dose was also not associated with HF (OR=0.96 per 100g increase in cumulative dose; 95% CI: 0.90-1.03). Furthermore, there was a lack of correlation between the duration of HCQ exposure prior to index and HF incidence (OR=0.98; 95% CI: 0.91-1.05). Retinal toxicity rates were similar in cases and controls.2
Dr. Sorour added, “The use of HCQ was not associated with the development of HF in patients with RA. There was also no statistically significant association between the cumulative dose of HCQ and HF.”
At the moment, Dr. Sorour and his team are assessing the echocardiography features of the HF patient case group. In reviewing the data, Dr. Sorour highlighted the need for extensive studies to determine safe HCQ dosage and treatment length. Notably, Dr. Sorour believes that quantification of HF-risk in other rheumatic diseases treated by HCQ, such as systemic lupus erythematosus, might facilitate a better understanding of the risk-benefit profile of HCQ.