Pre-existing heart failure affects safety of hydroxychloroquine in RA patients

Comparing methotrexate and hydroxychloroquine therapy for rheumatoid arthritis (RA) resulted in similar results for severe cardiovascular events or sudden cardiac death/ventricular arrhythmia. In case of a concomitant heart failure diagnosis, methotrexate appears to be a safer option in terms of mortality and cardiovascular events.

“In the US, hydroxychloroquine is commonly used as a first-line treatment in patients with RA, while methotrexate is the recommended first-line disease-modifying antirheumatic drug (DMARD),” Dr Elvira D’Andrea (Brigham and Women’s Hospital, MA, USA) stated [1]. In the wake of assessments on hydroxychloroquine use in COVID-19 patients, concerns regarding cardiovascular safety have been raised [2]. “We conducted a comprehensive cardiovascular safety evaluation of hydroxychloroquine compared with methotrexate in patients with RA,” Dr D’Andrea explained the aim of the presented research [1].

Data from Medicare linked to the National Death Index was used to identify a cohort of patients with RA starting on their first-line medication with either hydroxychloroquine or methotrexate. This led to 54,462 matched pairs in each group that were followed over a median time of 209 days. The composite primary outcome was defined as sudden cardiac arrest or ventricular arrhythmia and 3-point major adverse cardiovascular event. Secondary outcomes consisted of cardiovascular events as well as all-cause mortality, myocardial infarction, stroke, and hospitalised heart failure. The mean age of the cohort was 74.3 years, and 78.5% were women. Heart failure was known in 12% of the cases, and coronary artery disease in just over 24%.

In terms of the primary outcome, no significant difference was found between methotrexate (i.e. reference group) and hydroxychloroquine: HR 1.03 (95% CI 0.79–1.35) for sudden cardiac death/ventricular arrhythmia and HR 1.07 (95% CI 0.97–1.18) for major adverse cardiovascular events. The results for the secondary outcomes, however, revealed significant differences between the groups for cardiovascular and all-cause mortality. Patients treated with hydroxychloroquine had a 41% higher relative risk for heart failure hospitalisation and the HR for all-cause mortality was 1.10.

A subgroup analysis was additionally performed based on prior history of heart failure. No disparities were shown between methotrexate or hydroxychloroquine treatment in those without previously established heart failure, but they were found for hospitalisation due to heart failure (HR 1.63 in favour of methotrexate). “Hydroxychloroquine use appears to be associated with increased risk of major adverse cardiovascular events, cardiovascular mortality, all-cause mortality, and myocardial infarction in patients with a history of heart failure. An increased risk of hospitalisation for heart failure was observed in new users of hydroxychloroquine regardless of prior history of heart failure,” Dr D’Andrea said in her final remarks.

1. D’Andrea E. Cardiovascular risk of hydroxychloroquine in the treatment of a rheumatoid arthritis: a retrospective cohort study. Abstract L11, ACR Convergence 2021, 3–10 November.


2. Desmarais J, et al. Arthritis Rheumatol. 2021 Oct 26. Online ahead of print.

 

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Posted on 14 January, 2022