泼尼松＞10 mg/d增加红斑狼疮患者心血管风险

纽约——约翰霍普金斯大学的Michelle Petri博士在纽约大学主办的会议上报告称，泼尼松日剂量＞10 mg可使系统性红斑狼疮(SLE)患者的心血管事件(CVE)风险加倍。他建议，应尽最大努力确保红斑狼疮患者泼尼松用量<10 mg/d的临界值。

在这项旨在探索可能增加SLE患者CVE风险的因素的观察性队列研究中，研究者分析了霍普金斯狼疮队列中1,874例SLE患者的资料，该队列纳入了在23年期间(1987年4月~2010年6月)每季度在该中心就诊的患者。结果显示，在泼尼松用量为1~9 mg/d的患者中，共发生32例CVE，与普通人群预期发生率无显著差异。但10~19 mg/d患者的CVE风险显著增加[相对风险(RR)，2.4；P=0.002]，相当于20.2例/1,000(人·年)；用量≥20 mg/d的患者风险增加超过5倍(P＜0.001)，相当于35.4例/1,000(人·年)(Am. J. Epidemiol. 2012;176:708-19)。

校正年龄因素后，CVE发生率与病程无关，但与既往疾病平均活动度和目前抗双链DNA抗体水平存在关联。尽管既往累计用量≥36,500 mg(相当于10 mg/d泼尼松或类似药物使用≥10年)可使CVE发生率加倍(P=0.0066)，但过去服用而目前不使用糖皮质激素对CVE发生率没有影响。

研究者建议，为降低SLE患者的CVE风险，应对传统心血管风险因素(高血压、肥胖、高脂血症、吸烟和久坐生活方式)进行评估和控制。儿童和成人临床试验已表明，他汀类药物不能预防SLE患者动脉粥样硬化加速，小鼠实验也未见预防作用。吗替麦考酚酯(MMF)或许是一种潜在的治疗药物，但该药尚未被美国食品药品管理局(FDA)批准用于SLE治疗。尽管有一些证据显示MMF可减缓肾脏移植患者及小鼠动脉粥样硬化进程，但目前还没有临床研究支持该药物可用于SLE患者的治疗。Petri博士也不建议将MMF用于SLE患者，因为该药有一些警告信息(感染、淋巴瘤和恶性肿瘤、妊娠丢失和先天畸形、中性粒细胞减少症和红细胞发育不全、干扰口服避孕药等)。

研究者还指出，非甾体抗炎药物(NSAID)也与SLE患者心血管损伤风险增加66%相关，应避免使用类固醇和NSAID。上述结果也进一步凸显了对红斑狼疮新治疗药物的需求。

Petri博士是葛兰素史克公司的顾问。

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By: AMY ROTHMAN SCHONFELD, Cardiology News Digital Network

NEW YORK – Current use of prednisone above 10 mg/day more than doubles the risk of cardiovascular events in patients with systemic lupus erythematosus, according to a study conducted by Dr. Michelle Petri and her colleagues.

"Do everything you can to keep patients with lupus below the 10-mg/day cutoff for prednisone," said Dr. Petri, director of the Lupus Center at Johns Hopkins Hospital, Baltimore. She presented the results of her work at a meeting sponsored by New York University.

In an observational cohort study that explored factors that might increase the risk of cardiovascular events (CVEs) in people with systemic lupus erythematosus (SLE), Dr. Petri analyzed data from 1,874 SLE patients in the Hopkins Lupus Cohort who were seen quarterly at a single clinical center for more than 23 years (April 1987 to June 2010). In patients who took 1-9 mg/day of prednisone, 32 CVEs occurred, which was not significantly different from what would be expected in the general population. But once 10 mg/day was exceeded, the risk of having a CVE increased significantly in the 10- to 19-mg/day prednisone group (relative risk 2.4, P = .002), equivalent to a rate of 20.2/1,000 person-years). A more than a fivefold increase in risk was noted in those who took 20 mg or more per day (P less than .001), which was equivalent to 35.4/1,000 person-years (Am. J. Epidemiol. 2012;176:708-19).

After adjustment for age, CVE rates were not associated with disease duration, but were associated with average past levels of lupus disease activity and recent levels of circulating anti–double-stranded DNA. Past use of corticosteroids in the absence of current use did not affect CVE rates, although a cumulative past dose of 36,500 mg or more (equivalent to 10 or more years of prednisone 10 mg/day or equivalent) more than doubled the CVE rate (P = .0066).

To reduce cardiovascular risk in patients with SLE, Dr. Petri suggested assessing and treating traditional cardiovascular risk factors (hypertension, obesity, hyperlipidemia, smoking, and a sedentary lifestyle). Clinical trials in children and adults have shown that statins do not prevent accelerated atherosclerosis in SLE, so they are not helpful. "They don’t even work in mice!" said Dr. Petri, a professor in the division of rheumatology at Johns Hopkins University School of Medicine, Baltimore.

One possible treatment might be mycophenolate mofetil (MMF), which has not been approved by the Food and Drug Administration for use in SLE. Although there is some evidence that MMF slows progression of atherosclerosis in renal transplant patients and in mice, no clinical studies have been done to support its use in SLE. But Dr. Petri discouraged treating patients with MMF because of warnings associated with its use (infection, lymphoma and malignancies, pregnancy loss and congenital malformations, neutropenia and red cell aplasia, and interference with oral contraceptives).

NSAIDs have also been associated with a 66% increased risk of cardiovascular damage in SLE, Dr. Petri said. "These findings are a driving factor behind our need for new therapies for lupus. We need to avoid steroids as well as NSAIDs."

Dr. Petri is a consultant to GlaxoSmithKline.