Hydroxychloroquine has been linked with a significantly decreased risk for cardiovascular events, including venous thromboembolic events, among patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE), found a Canadian study.
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 after adjustment for comorbidities and other medication use, according to Dr J Antonio Avina-Zubieta of the University of British Columbia in Vancouver, and colleagues.
In addition, reports Medpage Today, 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 for various potential cardiovascular risk factors, such as hyperglycaemia and dyslipidaemia. And 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 people 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.
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), ischaemic stroke/transient ischaemic attack, or venous thromboembolism (deep vein thrombosis or pulmonary embolism).
Hydroxychloroquine use was categorised 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 before 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.
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 and 0.96 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 for MI and 0.87 for stroke/transient ischaemic 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 hyperlipidaemia 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 non-significant 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.
Study details
Hydroxychloroquine Use and Cardiovascular Events Among Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis
April Jorge, Na Lu, Hyon Choi, John Esdaile, Diane Lacaille, J. Antonio Avina-Zubieta
Published in Arthritis Care & Research on 23 December 2021
Abstract
Objective
We evaluated the potential temporal association between Hydroxychloroquine (HCQ) use and cardiovascular (CV) events among patients with SLE or RA.
Methods
We conducted a nested case-control study within inception cohorts of SLE and RA patients using administrative health databases including the entire population of British Columbia, Canada. We identified cases with incident CV events, including myocardial infarction (MI), stroke, or venous thromboembolism (VTE). We matched each case with up to three controls on age, sex, and rheumatic disease. HCQ exposure was categorised by the time between the last HCQ prescription date covered and the index date as current use, recent use, remote use, or never used. We used conditional logistic regression to assess the association between HCQ exposure and CV events, using remote use as the reference group.
Results
We identified 10,268 cases and 29,969 controls. Adjusted conditional odd ratios (cORs) (95% CI) for current HCQ use relative to remote use were 0.86 (0,77-0,.97) for combined CV events, 0,88 (0,74, 1.05) for MI, 0.87 (0,74, 1,03) for stroke, and 0,74 (0,59, 0,94) for VTE. Recent HCQ users and non-users had similar odds of combined CV events as remote users (cORs 0,93 ([95% CI, 0,77-1,13] and 0, 96 [95% CI, 0,88-1,04], respectively).
Conclusion
In this nested case-control study of patents with SLE and RA, we found a reduced risk of overall CV events associated with current HCQ use including reductions in VTE and trends towards reductions in MI and stroke. These findings suggest a possible cardiovascular preventative benefit of HCQ use.
Medpage Today article – Hydroxychloroquine Linked to Less Heart Risk in RA, Lupus (Open access)
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