Daily glucocorticoids exceeding 5 mg 'threshold' linked to higher cardiovascular risk in RA
Daily glucocorticoid doses of 5 mg or more during the preceding 6 or 12 months is associated with an increased risk for cardiovascular events in steroid-naïve patients with rheumatoid arthritis, according to data.
In addition, this risk increased with cumulative dose and duration of use. Meanwhile, the researchers found no association between cardiovascular risk and daily prednisone doses of 4 mg or less, or shorter cumulative doses and durations.
“Controversy exists regarding the risks and benefits of GC in RA patients,” Anthony James Ocon, MD, PhD, of the University of Rochester Medical Center, in New York, and colleagues wrote in the Annals of the Rheumatic Diseases. “Relative cardiovascular safety is generally assumed with lower dose and shorter durations of use, especially over short-term intervals. However, little data has actually been reported regarding the temporal effects of short-term interval GC use preceding cardiovascular events (CVE).”
“The 2016 and 2019 European League Against Rheumatism and 2015 and 2021 American College of Rheumatology recommend the use of ‘low-dose’ GC for ‘the least amount of time’ in combination with DMARDs for the treatment of RA,” they added. “Thus, it is important to determine the safety of initiating ‘low-dose’ GC in regard to the development of CVE. Furthermore, CVE in RA may be decreasing due to better control of disease activity following the widespread use of ts/bDMARDs, perhaps making the determination of the contribution of GC to CVE even more challenging in the present era.”
To examine whether starting glucocorticoids in steroid-naïve patients with RA increase cardiovascular risk in a dose- and duration-dependent way over a short-term period, Ocon and colleagues analyzed data from the CorEvitas — formerly Corrona — RA registry. The researchers collected data from between Oct. 1, 2001, and March 31, 2018, identifying 48,535 enrolled adults. After excluding patients with current or prior glucocorticoid use, 15 months between visits, or missing gender, age or disease duration data, as well as those without a follow-up visit, a total of 19,902 individuals were included in the analysis.
The researchers assessed glucocorticoid use based on current daily dose, cumulative dose and duration of use over rolling intervals of the preceding 6and 12 months. In addition, they used Cox proportional-hazards models to estimate adjusted hazard ratios for cardiovascular events in patients who started glucocorticoids, adjusting for RA duration, traditional cardiovascular risk factors and time-varying covariates, including clinical disease activity Index, disease-modifying antirheumatic drugs use and prednisone-equivalent use.
According to the researchers, there were 1,106 reported cardiovascular events, or 1.66 per 100 person-years. Increased adjusted hazard ratios were reported at current doses of 5 mg to9mg (1.56; 95% CI, 1.18-2.06) and at 10mg or more (1.91; 95% CI, 1.31-2.79). No increased risk was reported at doses of 0 mg to 4 mg (1.04; 95% CI, 0.55-1.59).
Cumulative dose during the preceding 6months demonstrated increased adjusted hazard ratios at 751 mg to 1,100mg (1.43; 95% CI, 1.04-1.98) and at 1,100mg or more (2.05; 95% CI, 1.42-2.94), without an increased risk at lower doses. Duration of use during the preceding 6months also demonstrated an increased adjusted hazard ratio, for greater than 81days of use (1.54; 95% CI, 1.08-2.32), without an increased risk at shorter durations. Twelve-month findings were consistent.
“We reported that daily doses of 5mg of prednisone-equivalents, elevated cumulative dose and extended duration of use of GC over the preceding 6-month and 1-year intervals are associated with an increased risk for incident CVE in steroid-naïve patients with RA,” Ocon and colleagues wrote. “We also emphasize the relative absence of CVE with dosing of 4mg per day, lower cumulative dose and a duration of use of only 6months prior to an event. Physicians treating patients with RA should consider these threshold ranges of GC use when prescribing prednisone as a part of a treat-to-target regimen.”