medwireNews: Hydroxychloroquine is not associated with an overall increased risk for sudden cardiac arrest or ventricular arrhythmia (SCA/VA) or major adverse cardiovascular events (MACE) relative to methotrexate among older people with rheumatoid arthritis (RA), study findings suggest.
However, Seoyoung Kim (Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA) and team found that the antimalarial was associated with an elevated risk for adverse cardiovascular (CV) outcomes when the analysis was restricted to patients with pre-existing heart failure (HF).
“Based on our findings, health care providers should be more cautious in prescribing hydroxychloroquine to older patients with baseline HF or at high risk for developing HF, paying careful attention to cardiac manifestations,” write the researchers in the Journal of the American College of Cardiology.
Kim et al used the Medicare database to evaluate CV risk in 27,231 people with RA aged 65 years or older who initiated hydroxychloroquine in 2008–2016, and the same number of propensity score-matched individuals who instead initiated methotrexate. Patients were aged an average of 74 years, 79% were women, and 12% had a history of HF.
During a median follow-up of 209 days, there were 102 SCA/VA events in the hydroxychloroquine group and 109 SCA/VA events in the methotrexate group, giving comparable event rates of 3.67 and 3.57 per 1000 person–years, respectively. Risk for MACE was also similar in the two groups, with a corresponding 820 and 839 cases, and rates of 29.91 and 27.81 per 1000 person–years.
In subgroup analyses, however, hydroxychloroquine was associated with a significantly higher risk for MACE than methotrexate (hazard ratio [HR]=1.30) in people with pre-existing HF, but not in those without.
Evaluation of secondary outcomes in the overall study population found a significantly increased risk for CV mortality (HR=1.17), all-cause mortality (HR=1.10), and hospitalization for HF (HR=1.41) with hydroxychloroquine versus methotrexate. Subgroup analysis showed that the increased risk for CV and all-cause mortality with hydroxychloroquine was restricted to those with a history of HF, whereas the increased risk for HF hospitalization was seen irrespective of prior HF.
Kim et al point out that “a potential cardioprotective activity of methotrexate” could explain their findings, so they conducted an exploratory sensitivity analysis comparing hydroxychloroquine with sulfasalazine in 5018 matched patient pairs. The results remained consistent in this analysis, but the researchers caution that the “statistical power to detect a difference was much lower in this comparison because of the small number of patients treated with sulfasalazine in clinical practice.”
The team concludes that “[f]urther research is needed to clarify the mechanisms responsible for the higher risk of cardiovascular complications and HF during hydroxychloroquine treatment.”
Writing in an accompanying editorial comment, E Blair Solow and Bonnie Bermas, both from the University of Texas Southwestern Medical Center in Dallas, USA, say that the lack of association between hydroxychloroquine use and arrhythmic events or MACE in the overall study population of older RA patients was reassuring.
They note that “the potential cardiovascular toxicity of [hydroxychloroquine] in younger patients […] warrants further exploration,” based on existing evidence suggesting that the agent “may be associated with reduced risk of coronary artery disease in patients with RA.”
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J Am Coll Cardiol 2022; 80: 36–46
J Am Coll Cardiol 2022; 80: 47–49