Rheumatoid Arthritis Treatment: Weighing the Cardiovascular Risks of Glucocorticoids
—Glucocorticoid treatment for rheumatoid arthritis is associated with an increased risk of cardiovascular disease in both younger patients and older patients with high CV risk and in older patients with more comorbidities, according to this study.
Treatment for rheumatoid arthritis (RA) is generally therapy with disease-modifying anti-rheumatic drugs (DMARDs). However, glucocorticoids are also used in the short term, particularly when just beginning a DMARD or switching to a different one.
In an interview with MedPageToday, Brian Coburn, MD, PhD, of the Division of Rheumatology at the University of Pennsylvania, said, “We know glucocorticoids can be useful for patients with RA, but glucocorticoids also have risks. In addition to considering the risks of infection or osteoporosis, clinicians may want to consider the association of glucocorticoids with increased cardiovascular (CV) risk.”
Despite this risk, it has been reported that approximately one-third of patients continue glucocorticoids long-term (>5 years).1 RA itself has an increased risk of CV disease;2,3 therefore, it is thought that controlling inflammation might decrease this risk.4 This needs to be weighed with the knowledge that some medications, such as glucocorticoids, even at low doses, may also increase CV risk whether or not a patient has an underlying high CV risk.5,6
Study overview and methodology
Dr. Coburn and colleagues investigated the CV risk of using low-dose glucocorticoids for patients with RA. They also looked at the CV risk of this use in patients with RA who also were at high risk for CV outcomes. Their report was published online in Arthritis & Rheumatology.4
Using Medicare and Clinformatics® Data Mart (CDM) (a commercial insurer) claims data, with a study index date from January 2007 through August 2015, the researchers included adult patients with RA who were on stable DMARD treatment. Treatment with glucocorticoids was classified as none, ≤ 5 mg/d, > 5 to 10 mg/d, and > 10 mg/d, with ≤ 5 mg/d defined as the low dose. The glucocorticoid dose was recalculated every 90 days. The main outcome of the study was the incidence of a first stroke or myocardial infarction (MI) (composite CV outcomes). The covariates that are associated with CV outcomes were measured during the baseline period (1 year). These included age, geographic demographics, smoking status, comorbidities, usage of healthcare, DMARD and other medication use, and immunization status.4
A total of 135,583 patients on Medicare and 39,272 patients in CDM were included in the study. Those in the Medicare group tended to be older than those in the CDM group (67.7 vs 56.4) and had more comorbidities. Of the CDM patients in the study, 10% were on targeted synthetic DMARDs and 40% were taking biologics. Of all the patients, 46.2% of the Medicare patients and 38.7% of the CDM patients were taking glucocorticoids (mostly low dose).4
Increased CV risk with glucocorticoid use
Regarding CV outcomes, the Medicare patients had a 1.3/100 person-years incidence of composite CV outcomes and the CDM patients had a 0.8/100 person-years incidence. Stroke contributed to the outcome in 56% of the Medicare patients and 50% in the CDM patients; MI contributed in 42% and 48%, in the Medicare and CDM patients, respectively. The unadjusted analysis showed that glucocorticoid use was associated with a dose-dependent increase in CV outcomes compared with no glucocorticoids. The adjusted model showed that this remained in the Medicare cohort, but not the CDM group.4
Looking at the high-risk patients—defined as those with a history of smoking, hypertension, hyperlipidemia, diabetes, or extra-articular RA in the year prior to index, or those who had a previous MI—the Medicare patients had a 2.1/100 person-years incidence of composite CV outcomes and the CDM patients had a 2.0/100 person-years incidence. The use of glucocorticoids was associated with an increase in the composite CV outcomes in both groups.4
Practical takeaways for clinicians
In reviewing the clinical implications of their study, Dr. Coburn said, “We can detect CV risk most easily among older adults and those at highest baseline CV risk. The CV risks found in our study reinforce the principle of keeping glucocorticoid use to the lowest dose over the shortest time possible to provide the needed benefit for patients with RA. For some patients, clinicians may also consider alternative options such as switching DMARD therapy instead of starting or prolonging glucocorticoid use.”
Dr. Coburn added, “This study doesn't imply that glucocorticoids should be completely avoided even in patients with high baseline CV risk. The potential increase in CV risk we saw was modest, but we do hope the results emphasize the importance of weighing the risks and benefits of glucocorticoids for each patient individually.”
Limitations
The investigators did mention several limitations to their study. The retrospective observational nature of the study may have the risk of confounding. Additionally, the study period ended in 2015; it is possible that there have been advances in the management of CV disease since that time. However, the authors also state that they do not think any changes would significantly alter the association between the use of low-dose glucocorticoids and CV outcomes. Several factors were not available to the investigators for the study, such as direct measures of disease activity for RA and details of exposures to smoking; these could alter their conclusions. Another limitation was the relatively short follow-up of less than 1 year. Finally, misclassifications of glucocorticoid doses, indications for taking the glucocorticoids, and outcomes could have occurred secondary to the data being from filled prescriptions and claims data.4
Future directions for research
In a discussion about the future and what studies should be done, Dr. Coburn told MedPageToday, “We need better methods to identify which patients are at highest risk of adverse CV outcomes from glucocorticoids. I would also like to see work focused on whether existing treatments with known CV benefits could reduce the increased risk we observed among high-risk patients with RA.”
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