FIELDS of dreams, fields of tears: a perspective on the fibrate trials
FIELDS of dreams, fields of tears: a perspective on the fibrate trials
复制标题
梦想的领域，泪水的领域：贝特类试验的视角
DOI：
--
复制
发表时间：
2006
影响因子：
2.6
通讯作者：
A. Wierzbicki
中科院分区：
文献类型：
--
作者：
A. Wierzbicki
自 1971 年以来，贝特类药物治疗冠心病的终点研究一直在进行。结果令人困惑——从小型研究中的初步益处开始，但与冠心病药物项目中的最小益处或世界卫生组织氯贝特研究中的不良非心血管 (non-CV) 作用相矛盾。退伍军人事务部 HDL 干预试验中发现，事件减少 25% 后，低 HDL-C 和低 LDL-C 患者重新使用贝特类药物。代谢综合征的脂质三联征的更大重要性和糖尿病患病率的增加增加了贝特类药物的应用性，因为它们的主要作用是将小密度低密度脂蛋白转化为轻浮性低密度脂蛋白。非诺贝特干预糖尿病事件降低（FIELD）研究继承了这一传统。对 9795 名混合低风险一级预防和中风险二级预防队列的患者进行非诺贝特治疗，使冠状动脉事件减少 11% (p = 0.16)，心血管事件也有类似但显着的减少 (p = 0.04；需要治疗的人数 = 70)。其益处集中在一级预防和非致命性心肌事件上，但由于非诺贝特的 LDL-C 降低作用，该研究因他汀类药物的不对称滴入而受到干扰。安全性总体上良好，包括与他汀类药物联合使用，但人们对猝死、胰腺炎和静脉血栓形成的担忧又回来了。非诺贝特对微血管终点（包括微量白蛋白尿和视网膜病变）具有意想不到的益处。非诺贝特是治疗糖尿病血脂异常的合理二线疗法，联合治疗是安全的。其对微血管疾病和联合治疗的益处需要进一步证实。
Endpoint studies have been performed with fibrates in coronary heart disease since 1971. The results have been confusing – starting with initial benefits in small studies, but contradicted by either minimal benefits in the Coronary Drug Project or adverse noncardiovascular (non‐CV) effects in the World Health Organization Clofibrate Study. Fibrates returned for patients with low HDL‐C and low LDL‐C after a 25% event reduction were seen in the Veterans Affairs HDL Intervention Trial. The greater prominence ascribed to the lipid triad of the metabolic syndrome and the increasing prevalence of diabetes increased the topicality of fibrates given their main action of converting small dense to light buoyant LDL. The Fenofibrate Intervention in Event Lowering in Diabetes (FIELD) Study has carried on the tradition. Fenofibrate therapy in 9795 patients comprising a mixed low‐risk primary and a medium‐risk secondary prevention cohort resulted in an 11% reduction in coronary events (p = 0.16), a similar but significant reduction in CV events (p = 0.04; number needed to treat = 70). The benefits were concentrated in primary prevention and on nonfatal myocardial events, but the study was confounded by asymmetrical statin drop‐in due to the LDL‐C‐lowering effect of fenofibrate. Safety was generally good, including in combination with statins, but old concerns about sudden death, pancreatitis and venous thrombosis returned. Unexpected benefits were seen with fenofibrate on microvascular endpoints including microalbuminuria and retinopathy. Fenofibrate is a reasonable second‐line therapy for dyslipidaemia in diabetes and safe in combination therapy. Its benefits on microvascular disease and in combination therapy require further confirmation.