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CV Risks of Hydroxychloroquine vs. Methotrexate in Rheumatoid Arthritis
Quick Takes
- Treatment with hydroxychloroquine was not associated with an increased risk of SCA/VA compared with methotrexate among all-comers with rheumatoid arthritis.
- Among those with a history of HF, hydroxychloroquine vs. methotrexate initiation was associated with increased risks of MACE, CV mortality, all-cause mortality, and MI.
- Clinicians should be circumspect in prescribing hydroxychloroquine to older patients with baseline HF or at high risk for developing HF, and carefully monitor cardiac manifestations.
Study Questions:
What is the cardiovascular (CV) safety of hydroxychloroquine compared to methotrexate among patients with rheumatoid arthritis (RA)?
Methods:
The investigators used Medicare data (2008–2016) and identified 54,462 propensity score–matched patients with RA, aged ≥65 years, who initiated hydroxychloroquine or methotrexate. Primary outcomes were sudden cardiac arrest or ventricular arrhythmia (SCA/VA) and major adverse cardiac events (MACE). Secondary outcomes were CV mortality, all-cause mortality, myocardial infarction (MI), stroke, and hospitalized heart failure (HF). The authors also examined treatment effect modification by history of HF. Cox proportional hazard models, with the exposure as independent variable, were used to estimate the hazard ratio (HR) and 95% confidence interval (CI). Kaplan-Meier curves were generated to visualize the cumulative incidence of the primary outcomes over time, and log-rank tests were used to compare hazard rates between treatment groups.
Results:
Hydroxychloroquine was not associated with risk of SCA/VA (HR, 1.03; 95% CI, 0.79-1.35) or MACE (HR, 1.07; 95% CI, 0.97-1.18) compared with methotrexate. In patients with history of HF, hydroxychloroquine initiators had a higher risk of MACE (HR, 1.30; 95% CI, 1.08-1.56), CV mortality (HR, 1.34; 95% CI, 1.06-1.70), all-cause mortality (HR, 1.22; 95% CI, 1.04-1.43), MI (HR, 1.74; 95% CI, 1.25-2.42), and hospitalized HF (HR, 1.29; 95% CI, 1.07-1.54) compared to methotrexate initiators. CV risks were not different in patients without history of HF except for an increased hospitalized HF risk (HR, 1.57; 95% CI, 1.30-1.90) among hydroxychloroquine initiators.
Conclusions:
The authors reported that in older patients with RA, hydroxychloroquine and methotrexate showed similar SCA/VA and MACE risks; however, hydroxychloroquine initiators with history of HF had higher risks of MACE, CV mortality, all-cause mortality, and MI.
Perspective:
This cohort study reported that treatment with hydroxychloroquine was not associated with an increased risk of SCA/VA compared with methotrexate among all-comers with RA. However, among those with a history of HF, hydroxychloroquine versus methotrexate initiation was associated with increased risks of MACE, CV mortality, all-cause mortality, and MI. Furthermore, an increased risk of hospitalization for HF was observed in initiators of hydroxychloroquine regardless of a prior history of HF. These findings suggest that clinicians should be circumspect in prescribing hydroxychloroquine to older patients with baseline HF or at high risk for developing HF, and carefully monitor cardiac manifestations. Additional studies are indicated to better understand the mechanisms responsible for the higher risk of CV complications and HF with hydroxychloroquine treatment.
Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Novel Agents, Statins, Acute Heart Failure
Keywords: Acute Coronary Syndrome, Arrhythmias, Cardiac, Arthritis, Rheumatoid, Death, Sudden, Cardiac, Geriatrics, Heart Failure, Hydroxychloroquine, Methotrexate, Myocardial Infarction, Pharmaceutical Preparations, Primary Prevention, Risk Assessment, Stroke, Vascular Diseases
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