Long-term low dose glucocorticoid therapy in rheumatoid arthritis: a systematic review with meta-analysis on cardiovascular effects.
Glucocorticoids (GCs) are widely used as first-line therapy in rheumatoid arthritis (RA) due to their rapid onset of action and strong efficacy. However, inappropriate use is associated with significant adverse effects. Long-term treatment with low doses has been considered relatively safe for most RA patients, although its cardiovascular (CV) impact remains controversial.
A systematic literature review was conducted using PubMed to evaluate the CV effects of long-term (≥12 months) low-dose GC therapy (<7.5 mg/day prednisone equivalent) in RA patients. Studies published between 2010 and 15 March 2026 were screened independently by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2 tool for randomised controlled trials. A meta-analysis was performed to estimate pooled hazard ratios (HRs) with 95% confidence intervals.
Ten studies were included in the review, of which five provided adjusted HRs suitable for meta-analysis. Long-term GC exposure even to low doses was associated with an increased risk of CV events (pooled HR 1.37; 95%CI 1.03-1.81; p=0.01). Substantial heterogeneity was observed among studies. Egger's test did not indicate significant publication bias.
Current evidence suggests that while short-term low-dose GC therapy may be relatively safe in selected RA patients, prolonged use and higher cumulative doses are associated with a slight increased CV risk, particularly in individuals with existing risk factors or comorbidities.
A systematic literature review was conducted using PubMed to evaluate the CV effects of long-term (≥12 months) low-dose GC therapy (<7.5 mg/day prednisone equivalent) in RA patients. Studies published between 2010 and 15 March 2026 were screened independently by two reviewers. Study quality was assessed using the Newcastle-Ottawa Scale for observational studies and the Cochrane Risk of Bias 2 tool for randomised controlled trials. A meta-analysis was performed to estimate pooled hazard ratios (HRs) with 95% confidence intervals.
Ten studies were included in the review, of which five provided adjusted HRs suitable for meta-analysis. Long-term GC exposure even to low doses was associated with an increased risk of CV events (pooled HR 1.37; 95%CI 1.03-1.81; p=0.01). Substantial heterogeneity was observed among studies. Egger's test did not indicate significant publication bias.
Current evidence suggests that while short-term low-dose GC therapy may be relatively safe in selected RA patients, prolonged use and higher cumulative doses are associated with a slight increased CV risk, particularly in individuals with existing risk factors or comorbidities.
Authors
Gotelli Gotelli, Campitiello Campitiello, Hysa Hysa, Soldano Soldano, Pizzorni Pizzorni, Paolino Paolino, Sulli Sulli, Smith Smith, Cutolo Cutolo
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