Immunosuppressive medications and hospitalization for cardiovascular events in patients with rheumatoid arthritis.
OBJECTIVE
The risk of cardiovascular disease (CVD) is increased in patients with rheumatoid arthritis (RA), most likely because of increased systemic inflammation. Prior research suggests that immunosuppressive medications may reduce the risk of CVD among RA patients. This study was undertaken to investigate the effects of various immunosuppressive medications on the risk of cardiovascular events among a group of older patients with RA.


METHODS
In this nested case-control study, the source cohort was derived from Medicare beneficiaries receiving a drug benefit from the state of Pennsylvania. These individuals were required to have been diagnosed as having RA on at least 2 visits and to have filled a prescription for an immunosuppressive agent. Cases were defined as those patients who were hospitalized for a cardiovascular event such as myocardial infarction or stroke, and 10 control subjects were matched to each case by age, sex, and calendar year of the index date (the time of the first cardiovascular event in each case). Current use of an immunosuppressive medication was defined as having filled a prescription for these agents within the 90 days prior to the index date. Multivariate logistic regression models that included important covariates were assessed to determine the risk of cardiovascular events associated with immunosuppressive agents and their combinations.


RESULTS
Among the study cohort, we identified 3,501 RA patients who fulfilled our eligibility criteria. During followup of this cohort, 946 patients were hospitalized for a cardiovascular event. Although the 95% confidence intervals (95% CIs) were wide in adjusted risk regression models with methotrexate (MTX) monotherapy as the reference group, biologic immunosuppressive agents showed neither protective nor deleterious effects (with biologics monotherapy, odds ratio [OR] 1.0, 95% CI 0.5-1.9; with biologics plus MTX combination therapy, OR 0.8, 95% CI 0.3-2.0; and with biologics plus other immunosuppressive agents, OR 1.2, 95% CI 0.7-2.2). Monotherapy with oral glucocorticoids was associated with an increased risk of cardiovascular events (OR 1.5, 95% CI 1.1-2.1), and a similar trend in the direction of risk was seen with glucocorticoid combination therapy (OR 1.3, 95% CI 0.8-2.0). Cytotoxic immunosuppressive agents other than MTX (azathioprine, cyclosporine, and leflunomide) were also associated with an increased risk of cardiovascular events (with both monotherapy and combination treatment, OR 1.8, 95% CI 1.1-3.0).


CONCLUSIONS
When compared with RA patients receiving MTX monotherapy, those receiving biologic immunosuppressive agents had neither an increased nor decreased risk of experiencing a cardiovascular event, whereas use of oral glucocorticoids and cytotoxic immunosuppressive agents was associated with significant increases in the risk of cardiovascular events.
Solomon
Daniel H
DH
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02120, USA. dhsolomon@partners.org
Avorn
Jerry
J
Katz
Jeffrey N
JN
Weinblatt
Michael E
ME
Setoguchi
Soko
S
Levin
Raisa
R
Schneeweiss
Sebastian
S
D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D006278:Medicare; D009203:Myocardial Infarction / Q000453:epidemiology; D010414:Pennsylvania / Q000453:epidemiology; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology
D018501:Antirheumatic Agents; D007166:Immunosuppressive Agents