SAN DIEGO – Even when taken at low doses and over short periods, glucocorticoids (GCs) were linked to a higher risk of major adverse cardiovascular events (MACE) over the long term in a Veterans Affairs population of older, mostly male patients with rheumatoid arthritis, a new retrospective cohort study has found.
The analysis of nearly 19,000 patients, presented by rheumatologist Beth Wallace, MD, MSc, at the annual meeting of the American College of Rheumatology, showed that the level of risk for MACE rose with the dose, duration, and recency of GC use, in which risk increased significantly at prednisone-equivalent doses as low as 5 mg/day, durations as short as 30 days, and with last use as long as 1 year before MACE.
University of Michigan
Dr. Beth Wallace
“Up to half of RA patients in the United States use long-term glucocorticoids despite previous work suggesting they increase MACE in a dose-dependent way,” said Dr. Wallace, assistant professor of medicine at the University of Michigan, Ann Arbor, and a rheumatologist at the VA Ann Arbor Healthcare Center. “Our group previously presented work suggesting that less than 14 days of glucocorticoid use in a 6-month period is associated with a two-thirds increase in odds of MACE over the following 6 months, with 90 days of use associated with more than twofold increase.”
In recent years, researchers such as Dr. Wallace have focused attention on the risks of GCs in RA. The American College of Rheumatology and the European Alliance of Associations for Rheumatology emphasize avoiding long-term use of GCs in RA and keeping doses as small and over the shortest amount of time as possible.
When Dr. Wallace and colleagues looked at the clinical pattern of GC use for patients with RA during the past 2 years, those who took 5 mg, 7.5 mg, and 10 mg daily doses for 30 days and had stopped at least a year before had risk for MACE that rose significantly by 3%, 5%, and 7%, respectively, compared with those who didn’t take GCs in the past 2 years.
While those increases were small, risk for MACE rose even more for those who took the same daily doses for 90 days, increasing 10%, 15%, and 21%, respectively. Researchers linked current ongoing use of GCs for the past 90 days to a 13%, 19%, and 27% higher risk for MACE at those respective doses.
The findings “add to the literature suggesting that there is some risk even with low-dose steroids,” said Michael George, MD, assistant professor of rheumatology and epidemiology at the University of Pennsylvania, Philadelphia, who did not take part in the research but is familiar with the findings.
Dr. Michael George
“We can see that even glucocorticoids taken several years ago may affect cardiovascular risk but that recent use has a bigger effect on risk,” Dr. George said in an interview. “This study also suggests that very low-dose use affects risk.”
For the new study, Dr. Wallace and colleagues examined a Veterans Affairs database and identified 18,882 patients with RA (mean age, 62.5 years; 84% male; 66% GC users) who met the criteria of being > 40 and < 90 years old. The subjects had an initial VA rheumatology visit during 2010-2018 and were excluded if they had a non-RA rheumatologic disorder, prior MACE, or heart failure. MACE was defined as MI, stroke/TIA, cardiac arrest, coronary revascularization, or death from CV cause.
A total of 16% of the cohort had the largest exposure to GCs, defined as use for 90 days or more; 23% had exposure of 14-89 days, and 14% had exposure of 1-13 days.
The median 5-year MACE risk at baseline was 5.3%, and 3,754 patients (19.9%) had high baseline MACE risk. Incident MACE occurred in 4.1% of patients, and the median time to MACE was 2.67 years (interquartile ratio, 1.26-4.45 years).
Covariates included factors such as age, race, sex, body mass index, smoking status, adjusted Elixhauser index, VA risk score for cardiovascular disease, cancer, hospitalization for infection, number of rheumatology clinic visits, and use of lipid-lowering drugs, opioids, methotrexate, biologics, and hydroxychloroquine.
Dr. Wallace noted limitations including the possibility of residual confounding and the influence of background cardiovascular risk. The study didn’t examine the clinical value of taking GCs or compare that to the potential risk. Nor did it examine cost or the risks and benefits of alternative therapeutic options.
A study released earlier this year suggested that patients taking daily prednisolone doses under 5 mg do not have a higher risk of MACE. Previous studies had reached conflicting results.
“Glucocorticoids can provide major benefits to patients, but these benefits must be balanced with the potential risks,” Dr. George said. At low doses, these risks may be small, but they are present. In many cases, escalating DMARD [disease-modifying antirheumatic drug] therapy may be safer than continuing glucocorticoids.”
He added that the risks of GCs may be especially high in older patients and in those who have cardiovascular risk factors: “Often biologics are avoided in these higher-risk patients. But in fact, in many cases biologics may be the safer choice.”
No study funding was reported. Dr. Wallace reported no relevant financial relationships, and some of the other authors reported various ties with industry. Dr. George reported research funding from GlaxoSmithKline and Janssen and consulting fees from AbbVie.