Setoguchi Soko, Schneeweiss Sebastian, Avorn Jerry, Katz Jeffrey N, Weinblatt Michael E, Levin Raisa, Solomon Daniel H
Divisions of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard MedicalSchool, Boston, MA 02130, USA.
Am Heart J. 2008 Aug;156(2):336-41. doi: 10.1016/j.ahj.2008.02.025. Epub 2008 Jun 17.
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.
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.
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).
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.
临床试验表明，肿瘤坏死因子-α拮抗剂（TNFAs）在晚期心力衰竭（HF）中获益甚微，且有些药物可能会造成潜在危害。尽管TNFAs在治疗类风湿关节炎（RA）方面有显著疗效，但对于老年RA患者使用此类药物是否会增加HF风险却知之甚少。
利用两个州（1994 - 2004年）医疗保险和药物福利项目的数据进行队列研究。我们确定年龄≥65岁且接受TNFAs或甲氨蝶呤（MTX）治疗的RA患者。该队列分为有和无既往HF的患者。我们考虑了人口统计学变量、心血管危险因素、与RA严重程度相关的指标以及其他合并症。主要终点是因HF住院。我们使用分层Cox比例风险回归来估计TNFAs对HF住院的调整效应。
该队列包括1002名TNFAs使用者和5593名MTX使用者。在使用TNFAs的1680人年中有59例HF入院，在使用MTX的10623人年中有227例HF入院。将TNFAs使用者与MTX使用者进行比较，HF住院的调整风险比为1.70（95%置信区间1.07 - 2.69）。在有和无既往HF的患者中我们发现了类似结果。在有既往HF的患者中，死亡的调整风险比为4.19（95%置信区间1.48 - 11.89）。
TNFAs可能会增加老年RA患者首次住院和HF病情加重的风险。我们的研究不能排除残留混杂因素的可能性；需要更大规模和更详细的研究来证实这些发现。
