Direction de la Stratégie, des Études et des Statistiques, Caisse Nationale de l'Assurance Maladie, Paris, France.
Pharmacoepidemiol Drug Saf. 2010 Dec;19(12):1256-62. doi: 10.1002/pds.2044. Epub 2010 Oct 13.
To evaluate and quantify in diabetic patients treated with benfluorex in France, a fenfluramine-derivated product, a possible increase in risk of valvular heart disease, previously suggested by several published case reports.
This was a French comparative cohort study using data from two large national linked databases, health insurance system (SNIIRAM) and hospitalization (PMSI). Patients aged 40-69 years with reimbursement for oral antidiabetic and/or insulin in 2006 were eligible. Exposed patients were defined as patients with at least one benfluorex reimbursement in 2006. Selected admission diagnoses of interest in 2007 and 2008 PMSI databases were valvular insufficiency for any cause, mitral insufficiency, aortic insufficiency, and valvular replacement surgery with cardiopulmonary bypass. Relative risks (RR) were adjusted on gender, age, and history of chronic cardiovascular disease.
A total of 1,048173 diabetic patients were included, with 43,044 (4.1%) exposed to benfluorex. The risk of hospitalization in 2007 and 2008 for any cardiac valvular insufficiency was higher in the benfluorex group: crude RR=2.9 [95% confidence interval 2.2-3.7] and adjusted RR=3.1 [2.4-4.0], with a lower risk for patients with lower cumulative dose of benfluorex. Adjusted RR for mitral insufficiency and aortic insufficiency admissions were 2.5 [1.9-3.7] and 4.4 [3.0-6.6], respectively. Adjusted RR for valvular replacement surgery was 3.9 [2.6-6.1].
Benfluorex in diabetic patients was significantly associated with hospitalization for valvular heart disease in the 2 years following benfluorex exposure. Linkage between SNIIRAM and PMSI databases is in France a valuable tool to quantify the risk of serious adverse drug reactions.
评估和量化在法国接受苯氟雷司治疗的糖尿病患者中，一种芬氟拉明衍生产品，可能会增加先前由几份已发表病例报告提示的瓣膜性心脏病风险。
这是一项法国比较队列研究，使用了两个大型国家关联数据库（健康保险系统（SNIIRAM）和住院（PMSI））的数据。2006 年有口服抗糖尿病药物和/或胰岛素报销的年龄在 40-69 岁的患者符合条件。暴露组患者定义为 2006 年至少有一次苯氟雷司报销的患者。2007 年和 2008 年 PMSI 数据库中选择的感兴趣的入院诊断为任何原因的瓣膜功能不全、二尖瓣功能不全、主动脉瓣功能不全和心肺旁路手术的瓣膜置换术。相对风险（RR）根据性别、年龄和慢性心血管疾病史进行调整。
共纳入 1048173 例糖尿病患者，其中 43044 例（4.1%）暴露于苯氟雷司。2007 年和 2008 年，苯氟雷司组因任何心脏瓣膜功能不全住院的风险更高：粗 RR=2.9 [95%置信区间 2.2-3.7]，调整 RR=3.1 [2.4-4.0]，累积剂量较低的患者风险较低。二尖瓣功能不全和主动脉瓣功能不全入院的调整 RR 分别为 2.5 [1.9-3.7]和 4.4 [3.0-6.6]。瓣膜置换术的调整 RR 为 3.9 [2.6-6.1]。
在接受苯氟雷司治疗后的 2 年内，糖尿病患者使用苯氟雷司与瓣膜性心脏病住院显著相关。SNIIRAM 和 PMSI 数据库之间的联系是法国量化严重药物不良反应风险的一种有价值的工具。
