Background/Purpose: Rheumatoid arthritis (RA) and systemic glucocorticoid (GC) use are associated with increased risk of cardiovascular disease. The latest RA management recommendations from the American College of Rheumatology (ACR, updated in 2021) and European Alliance of Associations for Rheumatology (EULAR, updated in 2022) are divergent in terms of GC use. Whether there exists a CV-safe dose or duration of GC in the treatment of RA is still debatable and of great clinical interest.

Methods: This was a population-based retrospective cohort study. RA patients without major MACE at baseline were recruited from a Hong Kong citywide database from 2006 to 2015, and followed till the end of 2018. The primary outcome was the first occurrence of a major adverse cardiovascular events (MACE). Cox regression analysis with time-varying covariates was used to evaluate the association of GC and MACE, adjusting for demographics, traditional CV risk factors, inflammatory markers and the usage of anti-rheumatic drugs.

Results: Among 12,233 RA patients with 105,826 patient-years of follow-up with a mean follow-up duration of 8.7 years, 860 (7.0%) developed MACE. The crude incidence rate was 8.13 per 1,000 person-years. The baseline characteristics of the subjects are summarized in Table 1. In the time-varying analyses after controlling for confounding factors, a daily prednisolone dose of ≥ 5mg significantly increased the risk of MACE (erythrocyte sedimentation rate [ESR] model: HR 2.02, 95%CI 1.72-2.37; C-reactive protein [CRP] model: HR 1.87, 95%CI 1.60-2.18), while a daily dose below 5mg was not associated with MACE risk, compared to no GC use. The adjusted hazard ratios (HRs) of all candidate covariates are summarized in the forest plots (Figure 1). The MACE-free Kaplan-Meier survival curves of the groups receiving different GC doses are shown in Figure 2. In patients receiving daily prednisolone ≥5mg, both intermediate- (up to 180 days) and long-term (longer than 180 days) use of prednisolone ≥5mg daily were significantly associated with increased risk of MACE, with an adjusted HR of 1.07 (p-value < 0.001) per month of GC use.

Conclusion: In this population-based real-world database, after controlling for multiple confounding factors, the use of GC was associated with up to two-fold increased risk of incident MACE on long term follow-up. No safe duration of use was found in patients receiving daily prednisolone ≥5mg.Very low dose prednisolone (< 5mg daily) did not appear to increase CV risk.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/systemic-glucocorticoids-are-associated-with-a-time-and-dose-dependent-risk-of-major-adverse-cardiovascular-event-in-patients-with-rheumatoid-arthritis-a-population-based-study/