'Just 30 days of glucocorticoid use' in RA spikes cardiovascular risk by 15% over 6 months
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Among patients with rheumatoid arthritis, 30 days of glucocorticoid use in 6 months is associated with 15% increased odds of major adverse cardiac events in the next 6 months, according to data presented at ACR Convergence 2021.
This association appears to be independent of baseline cardiovascular risk and certain measures of RA disease activity, the presenter said.
“Up to half of RA patients in the United States use long-term glucocorticoids, despite previous work suggesting they increase major cardiovascular events, or MACE, in a dose-dependent way” Beth Wallace, MD, MS, of the University of Michigan Medicine and the U.S. Veterans Affairs Ann Arbor Healthcare System, told attendees at the virtual meeting.
“Prior work suggests long-term glucocorticoid use is common among RA patients with traditional MACE risk factors, like hyperlipidemia, diabetes, hypertension and smoking, but we know little about the incremental effect of ongoing glucocorticoid use on MACE risk in RA, particularly as traditionally predisposed comorbidities might confound its assessment,” she added. “For example, RA patients who take steroids may be more likely to develop diabetes or hypertension, which, if not adjusted for, could confound an association between glucocorticoid exposure and MACE.”
To examine the incremental impact of glucocorticoid on major adverse cardiac events in RA, Wallace and colleagues conducted a retrospective cohort study of national VA administrative data. The researchers used this data to identify patients with RA and at least one rheumatology visit from 2013 to 2018, with the first post-diagnosis visit set as the index date. Patients were excluded if they were younger than 40 or older than 90 years, or if they had other rheumatic diseases, prior major adverse cardiac event, or congestive heart failure in the previous 5 years.
The researchers then used pharmacy data to determine the patients’ supply of glucocorticoids, in days, as well as claims to identify any incidents of major adverse cardiac events. A major event was defined as any acute myocardial infarction, stroke, transient ischemic attack, cardiac arrest or coronary revascularization. Analyses included multilevel logistic regression to evaluate the association between days’ supply of glucocorticoids dispensed in a 6-month period, as well as the lagged outcome of major adverse cardiac events during the subsequent 6 months.
Patients were censored after their first major adverse cardiac event. The researchers adjusted data for baseline covariates, including demographics, health care use and long-term glucocorticoid use of more than 90 days. Additional time-varying covariates included methotrexate and biologic use. Wallace and colleagues also adjusted for baseline cardiovascular risk, using the VA risk score for cardiovascular disease. This score uses medical and pharmacy claims, vital signs and laboratory results to calculate a continuous risk prediction estimate and categorize 5-year risk for major adverse cardiac events.
A total of 26,239 patients were included the analysis.
According to the researchers, the median risk for major adverse cardiac events at baseline, as determined by the VA risk score, was 5.7%, within the range for medium risk. Among the patients, 23% demonstrated a high risk on the VA score, at more 9%. In all, 23% of the overall study population — and 24% of those with high risk — received 90 days or more of glucocorticoids during the first year of follow-up. Major adverse cardiac events occurred in 3.2% of patients overall, and in 4.9% of those with a high risk score. The median time to major event was 25 months (IQR = 12-44).
After adjusting for all covariates, 30 days of glucocorticoid use in a 6-month period was associated with a 1.14 (95% CI, 1.1-1.19) increase in the odds of a major adverse cardiac event in the following 6 months.
“We again demonstrate that long-term glucocorticoid use is common in the RA population, even among patients at high risk for MACE, as determined by a validated risk score,” Wallace said. “We also see that just 30 days of glucocorticoid use in a 6-month period, even if discontinuous, is associated with a 15% increase in odds of MACE over the following 6-month period. This association appears to be independent of baseline MACE risk, as well as claims measures of RA disease activity, like biologic and methotrexate use.”
She added: “We are now conducting further studies to evaluate whether glucocorticoid exposure modifies the effect of other MACE risk factors on the risk of future MACE, the relationship between glucocorticoid exposure and second MACE among those who have had a prior MACE, and whether the association we have observed persists after more robust adjustment for disease activity, for example in a registry population.”
Perspective
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Jonathan M. Greer, MD, FACR, FACP
This study by Wallace and colleagues was elegantly designed in its attempt to adjust for numerous covariates including MACE risk factors in RA patients exposed to systemic glucocorticoids. Although this was a retrospective study, the 6-year review of over 25,000 patients enhances the face-validity of these results.
As we have seen with other studies implying an increased risk of cardiovascular disease in glucocorticoid-exposed patients, this study confirms an association in patients using steroids for a prolonged (30 day) period, with an increased risk of MACE over the following 6 months.
It is interesting to note, however, that the actual daily and cumulative dose of glucocorticoids received over a 30-day period was not reported. There may be a threshold, above which a certain dose may be of significance, whereas a lower daily/cumulative dose may be safe to use in RA patients who need better control of their disease. Stratification based on dose, therefore, would be helpful to ascertain if this threshold exists.
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Wallace B. Abstract 1428. Presented at: ACR Convergence 2021; November 5-9, 2021 (virtual meeting).
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