Tumor necrosis factor-alpha antagonist use and heart failure in elderly patients with rheumatoid arthritis - PubMed (original) (raw)

Tumor necrosis factor-alpha antagonist use and heart failure in elderly patients with rheumatoid arthritis

Soko Setoguchi et al. Am Heart J. 2008 Aug.

Abstract

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.

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Figures

Figure 1

Figure 1

The sensitivity analysis shows how imbalanced a confounding factor needs to be imbalanced and strongly associated with HF hospitalization to account for the observed increased risk for TNFA use solely on the basis of confounding. Each line splits the area into 2: the upper right area represents all parameter combinations of ORE and RRCD that would create confounding by an unmeasured factor strong enough to move the point estimate of the observed HR (HR = 1.7) to the null (HR = 1.0) or even lower, that is, make the association go away. Conversely, the area to the lower left represents all parameter combinations that would not be able to move the observed HR to the null. We assumed a prevalence of the confounder of 0.2. (A prevalence of 0.2 for the confounder was chosen because this level minimized the magnitude of the odds ratios needed to elevate the apparent risk.) To elevate the HR of TNFA from 1.0 to the observed value of 1.7, a highly imbalanced factor between TNFA users and MTX that is strongly associated with HF hospitalization has to be unmeasured in our data.

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