Hydroxychloroquine Linked to Less Heart Risk in RA, Lupus

Current use of hydroxychloroquine was associated with a significantly decreased risk for cardiovascular events among patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE), Canadian researchers found.

Compared with patients who had used hydroxychloroquine in the past but had discontinued the drug for at least a year, current users had an odds ratio for a cardiovascular event of 0.86 (95% CI 0.77-0.97) after adjustment for comorbidities and other medication use, according to J. Antonio Avina-Zubieta, MD, PhD, of the University of British Columbia in Vancouver, and colleagues.

In addition, significantly lower risks with hydroxychloroquine use were observed specifically for venous thromboembolic events, with an adjusted odds ratio of 0.74 (95% CI 0.59-0.94), the researchers reported online in Arthritis Care & Research.

While these systemic inflammatory conditions typically carry an elevated risk for early cardiovascular disease and mortality, observational studies have suggested that hydroxychloroquine use in these patients may have benefits on various potential cardiovascular risk factors, such as hyperglycemia and dyslipidemia. An in small studies, venous thromboembolic events occurred less often in SLE patients taking hydroxychloroquine.

To further explore the potential for cardiovascular risk reduction with hydroxychloroquine use in patients with these diseases, Avina-Zubieta and colleagues conducted a nested case-control study in a cohort of patients with incident RA or SLE among the entire population of British Columbia using data from the administrative database Population Data BC. Medication use was determined from the PharmaNet database.

The inception cohort included 64,012 adult patients with RA and 6,241 with SLE diagnosed from 1997 to 2015.

Each patient in the combined group who experienced an incident cardiovascular event was matched by age, sex, and type of rheumatic disease with three controls also from the inception cohort who did not have an event. Cardiovascular events included myocardial infarction (MI), ischemic stroke/transient ischemic attack, or venous thromboembolism (deep vein thrombosis or pulmonary embolism).

Hydroxychloroquine use was categorized as current; recent, if their prescription ended between 90 and 365 days before the index event; remote, if their prescription ended more than a year prior to the event; or never.

Variables included the Charlson comorbidity index, prior cardiovascular disease, chronic kidney disease, and use of cardiac medications, glucocorticoids, disease-modifying antirheumatic drugs, and biologics.

To avoid confounding by indication, the reference group for the analysis was remote users, with the assumption that the drug would have been indicated for those patients.

Among the combined RA and SLE cohorts’ 70,253 patients, there were 10,268 cases with cardiovascular events (9,736 with RA and 532 with SLE), who were matched with 29,969 controls without events (28,720 with RA and 1,249 with SLE).

Two-thirds of patients were women, and mean age at the time of the cardiovascular event was 74. Overall, cases had a higher Charlson comorbidity index (1.20 vs 1.04) and more use of cardiovascular medications (53.6% vs 42.9%).

The analysis revealed that both recent use and never use of hydroxychloroquine had similar risks for cardiovascular events as remote use, with odds ratios of 0.93 (95% CI 0.77-1.13) and 0.96 (95% CI 0.88-1.04), respectively. The observation that recent users had similar risks as remote users “may suggest a loss of benefits after hydroxychloroquine discontinuation which is of relevance to weighing the risks and benefits of continuing long-term use of hydroxychloroquine in patients with SLE or RA,” the authors cautioned.

For the individual types of cardiovascular events, only venous thromboembolic events showed a significantly reduced risk among current hydroxychloroquine users versus remote users. Nonetheless, the adjusted odds ratios were 0.88 (95% CI 0.74-1.05) for MI and 0.87 (95% CI 0.74-1.03) for stroke/transient ischemic attack, suggesting a trend towards lower risks for these events with current hydroxychloroquine use, the researchers noted.

With regard to risk for acute MI, “prior studies have linked hydroxychloroquine use with improvement in several risk factors for coronary artery disease, including hyperlipidemia and insulin resistance, indicating potential mechanisms for prevention of MI,” they wrote. “Prospective studies are warranted to confirm the possible benefit of hydroxychloroquine in preventing coronary artery disease and MI events in patients with rheumatic disease,” they added.

In a stratified analysis according to type of rheumatic disease, the risks for RA patients were similar to the overall analysis, but the findings were nonsignificant for the SLE group, which may reflect the smaller size of the SLE cohort and limited power for analysis.

A limitation of the study was its reliance on administrative data.