Association of Immunosuppressive Glomerular Disease Therapies With Cardiovascular Risk

Individuals with glomerular disease are at high risk of cardiovascular problems, including heart attack and stroke. Immunosuppressive therapies used to treat glomerular disease are thought to contribute to this risk, but their contribution remains unclear.

To address this knowledge gap, Mark Canney, MB, BCh, BAO, PhD, and colleagues conducted a retrospective cohort study of 1,912 adults from British Columbia, Canada. Of these participants, 759 had immunoglobulin A nephropathy, 540 had focal segmental glomerulosclerosis, 387 had membranous nephropathy, and 226 had minimal change disease. A total of 1,137 (59.5%) participants were male, and their mean (SD) age was 50.6 (16.8) years.

The researchers assessed the association between exposure to certain immunosuppressive medications and a composite outcome comprising coronary artery, cerebrovascular, and peripheral arterial events. They adjusted survival models for baseline cardiovascular risks, type of glomerular disease, estimated glomerular filtration rate (eGFR) and proteinuria over time. The median follow-up was 6.8 years, during which 212 (11.1%) participants experienced the primary outcome.

After adjustment for cardiovascular risk factors, exposure to corticosteroids was not significantly associated with the primary outcome.

In fully adjusted models, calcineurin inhibitor exposure was associated with a twofold increased risk of cardiovascular events. This was true at both 150 to 300 defined daily doses (DDD) (hazard ratio [HR], 2.98; 95% CI, 1.27-6.95) and 300 or more DDD (HR, 2.78; 95% CI, 1.32-5.84).

At a peak daily dose of 0.5 or more DDD, antimetabolite (azathioprine, mycophenolate mofetil, and mycophenolate sodium) was associated with a higher risk of cardiovascular events, even after adjusting for baseline risk factors and the type of glomerular disease. However, this was not the case after adjusting for time-varying eGFR and proteinuria (HR, 1.70; 95% CI, 0.91-3.20).

In a fully adjusted model, each 10 g of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of cardiovascular events (HR, 1.46; 95% CI, 1.22-1.75).

In summary, the authors wrote that “our findings suggest that immunosuppressive therapies used in the treatment of glomerular disease may have different cardiovascular risk profiles, which should be considered when deciding on immunosuppression for individual patients and as a safety endpoint in future clinical trials.”

Source: Kidney International