免疫抑制剂对类风湿关节炎病人心血管事件的影响

libbocratic

The impact of immunosuppressive medications on cardiovascular events in RA patients
TNF blockers not associated with increased or decreased risk of heart attack or stroke
免疫抑制剂对RA患者心血管事件的影响
心脏病或中风发生危险的增加或减少与TNF拮抗剂无相关性。
Patients with rheumatoid arthritis (RA) have an increased risk of heart attack and stroke. According to extensive evidence, the key driver for this increased risk of cardiovascular disease is the increased systemic inflammation characteristic of RA. Studies are less clear on whether medications that work to reduce RA's inflammatory symptoms provide protective benefits against cardiovascular events. Some data have suggested that the most potential biologic therapies, such as the TNF blockers, might reduce the risk of ischemic cardiovascular events.
类风湿性关节炎（RA）患者有着更高的心脏病及中风的危险性。大量的证据表明，RA患者心血管事件发生率高的关键因素是由于其系统性的炎症。目前，关于是否这些减轻RA炎症症状的药物可减少心血管事件的发生，还没有明确。一些资料表明，目前最有效的生物制剂，如肿瘤坏死因子拮抗剂（TNF-BA）可能改善心血管事件中的局部缺血症状。
To investigate, researchers at Harvard Medical School's Brigham and Women's Hospital compared the effects of a variety of immunosuppressive agents on cardiovascular events in a large sample of RA patients. Based on their findings, featured in the December 2006 issue of Arthritis & Rheumatism (http://www.interscience.wiley.com/journal/arthritis), TNF blockers were not associated with either a reduction or an increase in the risk of heart attack or stroke compared with the most commonly used RA treatment, methotrexate. While certain anti-inflammatory drugs appeared to exacerbate the risk of heart attack and stroke for RA patients, particularly among older women.
为了对此继进行研究，哈福大学医学院的Brigham女子医院的研究人员对不同的免疫抑制剂在大样本的RA患者心血管事件的影响进行了比较。他们的研究结果题名“为TNF拮抗剂与RA最常用的药物甲氨喋呤（MTX）相比，对于心脏病或中风的危险的增加或减少无明显相关性”，发表在2006年12月的Arthritis & Rheumatism杂志上。虽然某些抗炎药物增加老年妇女心脏病和中风的危险性。

Drawing on a database of Medicare patients receiving a drug benefit from the state of Pennsylvania, the researchers identified 946 individuals who had been diagnosed with RA, prescribed an immunosuppressive agent, and hospitalized for either heart attack or stroke within a six-year period. These patients were defined as case subjects for studying the role of anti-inflammatory RA therapies in the risk of cardiovascular disease. Each case subject was matched by age and gender to ten controls. The controls, a total of 9,460 RA patients, did not experience cardiovascular events during the delineated period. All the subjects were over age 65 and most were female and white.
基于宾夕法尼亚州从这些药物治疗中受益医保患者资料，研究人员从中选出946名确诊的使用免疫抑制剂的RA患者，要求在6年内因心脏病或中风住过院。这些患者被确认为研究对象，用于研究抗炎治疗在RA患者心血管疾病中的危险性。每例研究对象与10例对照组在年龄及性别上配对。9460例对照组RA患者，在规定时间内无心血管事件发生。所有研究对象年龄大于65岁，且大多是女性和白人。
Current therapy was defined by having a prescription filled 90 days prior to the date of the case subject's first cardiovascular event. Researchers then categorized the different drugs and analyzed their relationship to heart attack and stroke using standard risk regression models. Methotrexate (MTX) was considered individually and, as the most widely prescribed immunosuppressive agent, used as the reference group for other therapies.
目前的治疗规定，在研究对象第一次心血管事件发生前，治疗满90天。研究人员对不同的药物进行分类，并使用标准危险评估模型对不同药物和心脏病发作及中风的危险性进行分析。最常使用的免疫抑制剂MTX作为对照组被单独评估。
Compared with MTX, researchers found neither a protective nor detrimental cardiovascular impact for biologic agents, including the interleukin-1 receptor antagonist anakinra as well as the three TNF?blockers, adalimumab, etanercept, and infliximab. Oral glucocorticoids, steroid hormones like prednisone, were associated with a 50 percent increase in the probability of a cardiovascular event when taken alone; a similar trend in the direction of risk was seen with glucocorticoids combination therapy. Most significantly, cytotoxic agents, also known as disease-modifying antirheumatic drugs (DMARDs), were found to increase the likelihood of heart attack or stroke by 80 percent when used without other drugs. This finding applied to azathioprine, cyclosporine, and leflunomide.
研究人员发现，与MTX相比，生物制剂包括如白介素-1受体拮抗剂阿那白滞素以及三个TNF拮抗剂，阿达木单抗、依那西普、英夫利昔单抗，对心血管没有明显的损害或保护作用。当单独使用口服的糖皮质激素，类固醇激素如强的松时，可使心血管事件的发生的可能性增加50%；当联合使用糖皮质激素治疗时也有类似的影响。值得注意的是，被认为可改善病情的细胞毒药物，包括硫唑嘌呤（TZA）、环孢霉素A（CS-A）、来氟米特，当被单独使用时，也可使心脏病发生或中风的可能性增加80%。

Daniel Solomon, MD, MPH, the study's lead author and Associate Professor of Medicine at Brigham and Women's Hospital and Harvard Medical School, acknowledges that this study has several limitations. Given the data source--a huge healthcare utilization database--it was difficult to assess the severity of RA and the contribution of other cardiovascular risk factors, such as smoking and diet. Furthermore, the subjects were primarily elderly, with a mean age of 82, and in a frail state of health. \"Experimental designs, such as randomized clinical trials, would be very useful to better understand the effects of these agents on cardiovascular outcomes among patients with RA,\" Dr. Solomon reflects.
这项研究的负责人，哈福医学院和Brigham女子医院医学副教授、医学博士、公共卫生学硕士，所罗门丹尼尔，承认这项研究有一些局限性。鉴于极大的数据资源-一个巨大的医疗保健数据库-，很难对RA的严重性及其他心血管事件的危险因素如吸烟和肥胖的影响作出评估。此外，研究对象平均年龄82岁，且健康状况较差。Solomon博士说，实验设计，如随机临床实验将有助于更好的了解这些药物在RA患者心血管不良事件发生中的影响。