Low-dose steroids may not increase cardiovascular risk in rheumatoid arthritis

August 7, 2023|Federal Practitioner

FROM ANNALS OF THE RHEUMATIC DISEASES

A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).

Previous studies have shown a dose-dependent increase in the risk of all-cause and cardiovascular (CV) mortality above a 7.5- to 8-mg dose of prednisolone, but “the question of whether there is a CV-safe dose and duration of GC use remains a topic of debate,” senior author Lai-Shan Tam, MD, a professor in the department of medicine and therapeutics at the Chinese University of Hong Kong, told this news organization in an email.

Other studies of GCs and CV risk among RA patients have yielded conflicting results, especially for low-dose GCs. Findings from a 2020 study published in PLOS Medicine suggested that patients who had several immune-mediated inflammatory diseases – including RA – and who took less than a 5-mg prednisolone-equivalent dose daily had 74% higher risk for all-cause CVD, compared with nonusers. But results from a 2021 study published in Annals of the Rheumatic Diseases suggested that a daily prednisone dose of 4 mg or less did not increase cardiovascular events over a period of 6 months to 1 year.

These contradictory results were “primarily due to incomplete control of confounding variables, such as failure to adjust for C-reactive protein (CRP) levels,” Dr. Tam said. “Our study aimed to use a big data analytical approach to determine the effect of systemic GC dose and duration on the risk of major adverse cardiovascular events in patients with RA, while controlling for systemic inflammation, traditional CV risk factors, and other therapies.”

Is there a ‘safe’ dose for glucocorticoids?

To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.

The study was published in Annals of the Rheumatic Diseases.

The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.

This quantification of the risk for MACE according to GC dosing – particularly the increase in risk over time – “is incredibly helpful for counseling patients, because I think most patients would not opt for that risk category,” Christie Bartels, MD, who heads the division of rheumatology at the University of Wisconsin–Madison, told this news organization. She was not involved with the study.