Background In the last years, glucocorticoids given in addition to disease-modifying anti-rheumatic drugs (DMARDs) have been used as disease modifying therapy. The potential cardiovascular (CV) risk of exposure to GCs is a subject of controversy and debate. Bidirectional effect of GCs has been suggested as an unfavourable action through pro-atherogenic modulation of traditional CV risk factors may be counteracted by a positive CV impact through lowering RA-disease activity.
Objectives To examine the association between exposure to low-dose prednisolone in early RA and CV outcomes in a two-year randomized prednisolone trial, with follow-up for ten years.
Methods Retrieval of data from the BARFOT two-year randomized trial comparing prednisolone 7.5 mg/day in addition to DMARDs (P-group) with DMARD therapy alone (NoP-group) (1). In all 223 patients with RA and symptom duration ≤12 months who had no prior history of CV events were included. The end points were incident composite CV events, ischemic coronary artery and cerebrovascular events, which were tracked through the Swedish Hospital Discharge and Cause of Death Registries.
Results At inclusion, the treatment groups differed in age [P-group 50.6 (14.1) vs NoP-group 56.9 (13.0) years, p=0.001] but not sex, disease characteristics or traditional CV risk factors (body mass index, smoking, diabetes mellitus, hyperlipidaemia). The cumulative burden of disease within the first two years after inclusion was lower in the P-group. A good half of the patients in the P-group stopped prednisolone treatment at the two year-visit and a further fourth quarter after 4-5 years. Only 6% of subjects in the NoP-group initiated prednisolone therapy. From the two-year follow-up visit to the last assessment, the traditional CV risk factors were evenly distributed in the treatment groups, except for diabetes mellitus, 2% in the P-group vs 9% in the NoP-group, p=0.017.
During 2041 person-years of observation, the total number of incident CV events was in the P-group 17/112 patients (15%), and in the NoP-group 15/111 patients (14%). The age-adjusted hazards for the incident composite CV event and ischemic coronary artery event did not differ significantly between the treatment groups, HRs (95% CI) of 1.8 (0.9-3.6), and 0.98 (0.4-2.6), respectively. The risk for incident cerebrovascular event showed a 3.7-fold hazard (95% CI, 1.2-11.4) among prednisolone treated patients as compared with those not treated with prednisolone. Addition of measures of disease activity to the Cox proportional hazard models did not change the results.
Conclusions The two-year exposure to a fixed low-dose of prednisolone in patients with early RA may affect the risk of ischemic cerebrovascular events. The results must though be interpreted in its context, as the population of this study was relatively young and had a low frequency of traditional CV risk factors.
Svensson B, Boonen A, Albertsson K, van der Heijde D, Keller C, Hafström I. Arthritis Rheum 2005; 52:3360-70.
Disclosure of Interest : None declared