Treatment with hydroxychloroquine was not associated with heart failure in patients with rheumatoid arthritis in a recent study; however, more research is needed regarding higher doses, according to a presenter at the EULAR 2020 E-Congress.
“Literature have argued over the cardioprotective and cardiotoxic role of hydroxychloroquine,” Ahmed A. Sorour, of the Mayo Clinic in Rochester, Minnesota, said in the online session. “Heart failure is a rare adverse effect attributed to the drug, but these data have been limited to case reports or series. Knowledge gaps exist on the risk for heart failure in RA patients using hydroxychloroquine.”
To analyze the association between hydroxychloroquine and the risk for heart failure among patients with RA, Sorour and colleagues conducted a nested case-control study of cases among residents of Olmsted County, Minnesota, residents from 1980 to 2013. The researchers enrolled 1,078 participants, including 143 patients with RA and subsequently developed heart failure, and 143 control individuals with RA only. Data on hydroxychloroquine use, including start and stop dates as well as dose changes, were accessed through medical record review.
Investigators matched each participant with RA who developed heart failure to a member of the control group based on birth year, sex and year of RA incidence. They also assigned each control member an index date corresponding to the heart failure diagnosis date of their match. Participants in the control group who later developed heart failure were allowed to switch groups.
Researchers defined heart failure using the Framingham criteria and used age-adjusted logistic regression models to examine the association between the drug and heart failure.
According to Sorour, both groups demonstrated similar RA duration, proportions of patients who were positive for rheumatoid factor and/or cyclic citrullinated antibody (CCP), BMI and smoking status. The duration of hydroxychloroquine use prior to index date was 2.8 years among those who developed heart failure and 2.6 years among those in the control group.
Seventy-one participants with heart failure and 69 individuals without heart failure used the drug at some time prior to the index date. Among these patients, the median duration of hydroxychloroquine use was 2.8 years for among those with heart failure, and 2.5 for those with RA only.
The median cumulative dose was 371 g among patients who eventually developed heart failure, and 302 g in the control group, with 55% of cases receiving a cumulative dose of 300 g or more in the case group, compared with 54% among the controls.
According to the researchers, cumulative dose was not associated with heart failure (OR = 0.96 per 100 g increase in cumulative dose; 95% CI, 0.9-1.03). Nor was there any association between heart failure and reaching a cumulative dose 300 g or more (OR = 0.92; 95% CI, 0.41-2.08). Treatment duration prior to the index date was also not associated with heart failure (OR = 0.98; 95% CI, 0.91-1.05). Retinal toxicity rates were similar in both groups.
“This study found that the use of hydroxychloroquine was not associated with the development of heart failure in patients with rheumatoid arthritis,” Sorour said. “There was also no statistically significant association between the cumulative dose of hydroxychloroquine and heart failure. We hope that this work can be the first step on a long road, as we still need to understand the risk of higher doses of hydroxychloroquine, and have a better assessment of patient compliance to medication.”
“Those larger studies are needed to help identify a safe dosage and duration of treatment with regard to heart failure,” he added. “It will be interesting to quantify the risk for heart failure in other rheumatic diseases treated by hydroxychloroquine, such as systemic lupus erythematosus.”