Antimalarial Medication Adherence Significantly Lowers Cardiovascular Risk Among Patients With RA and SLE

Regular adherence to antimalarial medication among individuals with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) has been shown to significantly lower cardiovascular risk over time, according to study results published in Arthritis Care & Research.

Chronic inflammatory autoimmune diseases such as RA and SLE are associated with an increased risk for inflammatory complications, notably, cardiovascular disease. Long term maintenance of these conditions consists mainly of treatment with antimalarial medications. The added lipid lowering, anti-inflammatory, and hypoglycemic effects of these drugs can further attenuate cardiovascular risk. To quantify this benefit, researchers investigated cardiovascular outcomes among patients with RA and SLE in relation to antimalarial adherence.

A retrospective, longitudinal cohort study was conducted in British Columbia, Canada. Adult patients aged at least 18 years with newly diagnosed RA or SLE who were prescribed antimalarial medications at least once without experiencing a cardiovascular event were included in the analysis.

Population Data BC (PopData), an electronic medical tracking record for all residents, was used to collect patient data on outpatient visits, hospitalizations, demographic information, and comprehensive information on prescription medications. Individuals were tracked for medical adherence based on the first day receiving an antimalarial drug and at 90-day interval windows thereafter. Adherence was calculated as a proportion of time when medication was taken as prescribed.

The composite primary study outcome was incident cardiovascular events, including myocardial infarction (MI), ischemic stroke, and venous thromboembolism (VTE).

A total of 16,538 individuals treated with antimalarials, of whom 14,644 (88.5%) were diagnosed with RA and 1894 (11.5%) with SLE, were included in the study. The median number of 90-day follow-up windows for all patients was 33 (mean, 35).

A cumulative 22% antimalarial adherence rate was noted for all 90-day windows of exposure among patients with RA and SLE, with 59% categorized as discontinuation, and 19% as nonadherence. Over the mean follow-up time of 9 years, 2174 (13.2%) patients experienced an incident cardiovascular event. A majority of those events were associated with antimalarial discontinuation (n=1394).

The adjusted hazard ratio (aHR) for incident cardiovascular events for antimalarial adherence relative to discontinuation was 0.72 (95% CI, 0.64-0.81), and 1.01 (95% CI, 0.90-1.14) for nonadherence relative to discontinuation. Estimates were not statistically different between the antimalarial discontinuation and nonadherence groups.

Patients with RA and SLE who did adhere to antimalarial therapy were found to have a 29% lower risk for incident cardiovascular events, compared against those who did not adhere to treatment (aHR, 0.71; 95% CI, 0.61-0.82).

When stratified according to specific cardiovascular event, antimalarial adherence was found to have a comparable risk reduction, with a 38% lower risk for MI (aHR, 0.62; 95% CI, 0.51-0.75), a 55% lower risk for stroke (aHR, 0.45; 95% CI, 0.36-0.58), and a 35% lower risk for VTE (aHR, 0.65; 95% CI, 0.46-0.93), when compared with nonadherence.

A secondary analysis using an 80% cut-off for antimalarial adherence was shown to have similar findings; the aHRs for incident cardiovascular events for antimalarial adherence compared with nonadherence was 0.74 (95% CI, 0.66-0.82) and 1.09 (95% CI, 0.96-1.24), respectively.

Of note, stratified analyses by disease type and sex did not show any effect modification, except for age group. The relative risk reduction of incident cardiovascular events among patients aged at least 65 years was significantly greater compared with those aged less than 65 years, when comparing antimalarial adherence with nonadherence (risk reduction, 41% vs 17%; P =.02).

This study was limited by a lack of data on reasons for antimalarial nonadherence and discontinuation, as well as unmeasured lifestyle factors contributing to adherence. Additional risk factors for cardiovascular events, such as disease activity, body mass index, smoking, and alcohol consumption were unavailable in the data.

The study authors concluded, “The protective effect of antimalarial was found to be lost

when adhering to less than 90% of the prescribed doses, and a greater degree of protection was observed in older patients. Therefore, enhancing medication adherence should be incorporated into appropriate screening strategies targeting high-risk populations (e.g., assessment for antiphospholipid antibodies in SLE) and encouraging compliance from patients to nonpharmacologic measures.”