Seoyoung C. Kim, MD, ScD, MSCE: Cardiovascular Risks with Hydroxychloroquine in Rheumatoid Arthritis

An interview on new findings suggesting baseline heart failure may be an indicator of increased mortality risk in patients treating arthritis with the DMARD.

A new late-breaking study presented at the American College of Rheumatology (ACR) 2021 Convergence showed disease-modifying antirheumatic drug (DMARD) hydroxychloroquine is not associated with risks of sudden cardiac arrest, ventricular arrhythmia, or major adverse cardiovascular events versus methotrexate in patients with rheumatoid arthritis.

The findings, from a team of Brigham and Women’s Hospital and Harvard University investigators, did find though that patients with both rheumatoid arthritis and a history of heart failure were at greater risk of cardiovascular events and related mortality when treated with hydroxychloroquine over methotrexate.

In an interview with HCPLive during ACR 2021, study senior author Seoyoung C. Kim, MD, ScD, MSCE, Associate Professor of Medicine in the Divisions of Pharmacoepidemiology & Pharmacoeconomics and Rheumatology, Inflammation, and Immunity, discussed the new findings and their contribution to interpreting cardiovascular risk with DMARD therapy.

HCPLive: How influential was the emergence of hydroxychloroquine as a potential treatment for COVID-19 in 2020 in your team’s pursuit of this research?

Kim: We actually started studying the cardiovascular (CV) safety before March 2020, but added a few more endpoints after hydroxychloroquine (HCQ) toxicity became the focus of many more people due to COVID-19. As the dose that we generally use for rheumatoid arthritis (RA) is lower than what people had used HCQ last year for COVID-19, even before we saw the study results, we were not particularly concerned about CV toxicity of HCQ.

The most common question I will be getting about this study will be something like, “Will RA patients who use HCQ have milder RA than those who take methotrexate (MTX)?” While our RWD analysis cannot fully account for confounding, we accounted for many baseline covariates using propensity score matching and such confounding (milder RA activity in HCQ vs MTX) cannot explain the directions of HRs listed in Table 2 of our ACR poster completely.

What was the previously understood correlation between DMARD treatment and risk of sudden cardiac arrest or ventricular arrhythmia?

Very limited evidence exists for the risk of sudden cardiac death or ventricular arrhythmias associated with any DMARDs. These events are rare (fortunately), so it is challenging to conduct a study with adequate power. As our study included 54,463 older patients with RA, we were able to observe many events during the follow-up time.

What were some of the most surprising outcomes of your team’s findings, if any?

We were somewhat surprised—although HF is a known concern for HCQ use—to see the increased HRs for CV mortality, all cause-mortality and hospitalized HF associated with HCQ use. It is also important to note that HCQ is associated with an increased risk of hospitalized HF in RA patients with and without history of HF.

How do these findings inform future prescribing strategies with hydroxychloroquine and/or methotrexate?

Based on our subgroup analysis by history of HF, rheumatologists—including myself—should be more cautious in using HCQ or avoid prescribing HCQ in patients with baseline HF.

What more needs to be researched on the basis of these findings?

Our study cohort is based on Medicare enrollees; therefore, the mean age is 74 years. I think it will be clinically important to further examine CV safety of HCQ vs. MTX in younger patients. While one wants to know the effect of HCQ vs. no other DMARDs (ie, non-user of HCQ), such comparison in non-randomized settings will not be valid; thus, it should not be conducted in non-randomized settings.

The study, “Cardiovascular Risk of Hydroxychloroquine in the Treatment of Rheumatoid Arthritis: A Retrospective Cohort Study,” was presented at ACR 2021.