Tumor necrosis factor-alpha antagonist use and heart failure in elderly patients with rheumatoid arthritis.
BACKGROUND
Clinical trials have shown that tumor necrosis factor-alpha antagonists (TNFAs) confer little benefit, and some may cause potential harm in advanced heart failure (HF). Although TNFAs had significant benefits in treating rheumatoid arthritis (RA), little is known whether the drugs pose an increased risk of HF in older patients with RA.


METHODS
A cohort study was conducted using data from Medicare and drug benefit programs in 2 states (1994-2004). We identified patients with RA aged > or =65 who received TNFA or methotrexate (MTX). The cohort was divided into patients with and without previous HF. We considered demographic variables, cardiovascular risk factors, RA severity-related measures, and other comorbidities. The primary end point was hospitalization with HF. We used stratified Cox proportional hazards regression to estimate the adjusted effect of TNFAs on HF hospitalization.


RESULTS
The cohort consisted of 1,002 TNFA users and 5,593 MTX users. There were 59 HF admissions during 1,680 person-years of TNFA use and 227 HF admissions during 10,623 person-years of MTX use. Comparing TNFA with MTX users, the adjusted hazard ratio for HF hospitalization was 1.70 (95% confidence interval 1.07-2.69). We found similar results in patients with and without previous HF. Among patients with previous HF, the adjusted hazard ratio for death was 4.19 (95% confidence interval 1.48-11.89).


CONCLUSIONS
TNFAs may increase the risk of both first hospitalization and exacerbation of HF in elderly patients with RA. The potential for residual confounding in our study cannot be ruled out; larger and more detailed studies are needed to confirm the findings.
Setoguchi
Soko
S
Divisions of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard MedicalSchool, Boston, MA 02130, USA. ssetoguchi@partners.org <ssetoguchi@partners.org>
Schneeweiss
Sebastian
S
Avorn
Jerry
J
Katz
Jeffrey N
JN
Weinblatt
Michael E
ME
Levin
Raisa
R
Solomon
Daniel H
DH
D000367:Age Factors; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy*; D015331:Cohort Studies; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006333:Heart Failure / Q000209:etiology* / Q000401:mortality; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D008727:Methotrexate