Hydroxychloroquine use does not increase risk of heart failure in RA patients

Use of hydroxychloroquine (HCQ) does not contribute to the development of heart failure (HF) in patients with rheumatoid arthritis (RA), a study has shown.

“[T]his is the first population-based study to quantify the association between HCQ use and HF in patients with RA, to our knowledge,” the researchers said. “We found no increased risk of HF in this RA population receiving HCQ.”

This nested case-control study identified residents of Olmsted County, Minnesota, US, with incident RA, based on the 1987 American College of Rheumatology criteria, from 1980 to 2013 who developed HF after RA incidence. Each case was matched based on birth year, sex, and year of RA incidence with an RA control who did not develop HF.

The researchers then reviewed data on HCQ use, including start and stop dates, as well as dose changes. They used these data to calculate HCQ duration and cumulative dose. Finally, the association between HCQ and HF was examined using age-adjusted logistic regression models.

Overall, 143 individuals with RA and diagnosed with HF (mean age 65.8 years, 62 percent females) and 143 non-HF RA controls (mean age 64.5 years, 62 percent female) were included in the analysis.

HCQ cumulative dose did not have a significant impact on HF risk (odds ratio [OR], 0.96 per 100-g increase in cumulative dose, 95 percent confidence interval [CI], 0.90–1.03). There was also no association found for patients with a cumulative dose ≥300 g (OR, 0.92, 95 percent CI, 0.41–2.08). [J Rheumatol 2021;48:1508-1511]

In addition, the duration of HCQ use in years prior to index showed no meaningful relationship with HF (OR, 0.98, 95 percent CI, 0.91–1.05).

“The inflammatory burden characteristic of RA has been linked to the increased risk of cardiovascular (CV) disease, including HF,” the researchers said. “HF development in patients with RA is multifactorial, with contribution from CV risk factors and RA disease-related factors.” [Arthritis Rheum 2005;52:412-420; Arthritis Rheum 2005;52:3039-3044]

Notably, a meta-analysis focusing on the association of HCQ and chloroquine use with CV risk in rheumatic patients revealed a reduced risk of CV disease development among HCQ users. [Drug Des Devel Ther 2018;12:1685-1695]

Some studies suggested that HCQ use had the following cardiotoxic effects: conduction disorders, restrictive cardiomyopathy, left ventricular hypertrophy, ventricular dysfunction, and valvular abnormalities. [Drug Saf 2018;41:919-931; Immunopharmacol Immunotoxicol 2013;35:434-442]

This evidence was drawn primarily from case reports/series and drug surveillance reports instead of population-based longitudinal data. However, two rationales supported such indications.

“First, HCQ cardiotoxicity has been characterized for its specific histological appearance on endomyocardial biopsy. Second, improvement after withdrawal of HCQ has been reported both clinically and histologically,” the researchers said. [N Engl J Med 1987;316:191-193; Eur J Echocardiogr 2007;8:247-251; Eur Heart J Acute Cardiovasc Care 2013;2:77-83]

“Larger prospective studies are needed to define the safety of higher cumulative doses of HCQ with regard to HF development, as well as to identify the incidence of HCQ-related cardiotoxicity in patients with RA, in order to define the subgroups of high-risk patients and the need for cardiovascular screening,” they noted.