High Cardiovascular Burden from Glucocorticoid Exposure in Giant Cell Arteritis: A Retrospective Cohort Analysis

Objectives Giant cell arteritis (GCA) is the most common type of vasculitis in adults, with high morbidity including cardiovascular disease (CVD). [1] Although tocilizumab and upadacitinib are approved for use in GCA, many patients remain dependent on high cumulative glucocorticoid doses, exposing them to the risk of cardiovascular toxicity.[2] Population-based data on glucocorticoid-associated CVD risk in GCA is scarce. We aimed to assess the association between glucocorticoid exposure and the risk of CVD in patients with GCA at the population level. Methods We used administrative data from British Columbia (BC), including all outpatient and hospital visits, all dispensed medications, vital statistics, demographics, and cancer registry. We assembled a population-based retrospective cohort of GCA with incident glucocorticoid use. Sample: all newly diagnosed GCA patients receiving healthcare between January 1997-December 2023 with no glucocorticoid exposure and no CVD events prior to GCA onset. GCA was defined by ≥1 code for GCA by a rheumatologist or hospital (ICD-9-CM 446.5; ICD-10 M31.5), or 2 ICD-9-CM codes for GCA between ≥2 months-2 years apart by a non-rheumatologist physician. Exposure: glucocorticoid dosing was calculated using Pharmanet data. Exposure was categorized as current use (Yes/No), current dose (mg/day), total past cumulative dose (grams), and total cumulative duration of use(months). Outcomes: We identified CVD outcomes using inpatient and outpatient ICD-9 billing codes, including myocardial infarction (MI) (ICD-9 410), stroke (434), and venous thromboembolism (VTE: DVT and PE) (453, 415.1, 673.2, 639.6). Associations between glucocorticoid exposure and CVD were estimated using a Cox proportional hazard model, adjusted for relevant confounders as in our previous studies. Results 4,681 patients with newly diagnosed GCA were identified with incident glucocorticoid use and no prevalent CVD (mean age 70.4, 68.9% female), with a mean Charlson comorbidity score of 0.94 (SD 1.58). During follow-up, we identified 969 CVD events (439 MI, 645 stroke, 134 VTE). Compared to non-users, glucocorticoid use was associated with a 113% increase in risk of CVD (Table 1). Moreover, current daily dose (15% per each 5 mg) and cumulative glucocorticoid dose (78% per each gram accumulated in the past) were associated with an increased risk of CVD. Cumulative duration of glucocorticoid use was also associated with a 23% increased risk of CVD per each month of use. Table 1. Increased Risk of Cardiovascular Disease from Glucocorticoid Exposure: Unadjusted and Adjusted Cox Proportional Hazard Models Conclusion Among patients with GCA, glucocorticoid use, daily dose, cumulative dose, and cumulative duration were significantly associated with increased risk of CVD. New strategies with newer therapies should target minimizing glucocorticoid use in patients with GCA. References [1.] Aviña-Zubieta JA. Ann Rheum Dis 2016;75:148-54. [2.] Pujades-Rodriguez M. PLoS Med 2020;17:e1003432.