Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial
Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial
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DOI：
10.1016/s0140-6736(07)61607-9
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发表时间：
2007-11-17
期刊：
影响因子：
168.9
通讯作者：
Colman, P. G.
中科院分区：
文献类型：
--
作者：
Keech, A. C.;Mitchell, P.;Colman, P. G.
背景糖尿病视网膜病变的激光治疗通常与视野缩小和其他眼部副作用有关。我们的目的是评估非诺贝特长期降脂治疗是否可以减少2型糖尿病患者视网膜病变的进展以及对激光治疗的需求。方法非诺贝特干预和降低糖尿病事件（FIELD）研究是一项多国随机试验，纳入了9795名年龄在50-75岁之间的2型糖尿病患者。符合条件的患者被随机分配接受非诺贝特200 mg/天（n=4895）或匹配的安慰剂（n=4900）。在每次临床访视时，收集了关于糖尿病视网膜病变激光治疗的信息--主研究预先规定的第三终点。由眼科医生对治疗分配设盲，对黄斑水肿、增生性视网膜病变或其他眼部疾病的激光治疗进行裁定。在一项包含1012例患者的子研究中，进行了标准化视网膜摄影，并根据早期治疗糖尿病视网膜病变研究（ETDRS）标准对照片进行分级，以确定糖尿病视网膜病变及其组成病变的累积发病率。本研究注册为国际标准随机对照试验，编号ISRCTN 64783481。结果：与血糖或血压控制良好的受试者相比，血糖或血压控制较差的受试者更需要激光治疗，而临床微血管疾病负担更大的受试者，但对这种治疗的需要不受血浆脂质浓度的影响。非诺贝特组对所有视网膜病变首次激光治疗的需求显著低于安慰剂组（非诺贝特组164例[3.4%]患者vs安慰剂组238例[4.9%]患者;风险比[HR] 0.69，95% CI 0.56.0.84; p=0.0002;绝对风险降低1.5% [0.7-2.3]）。在眼科子研究中，两组总体（非诺贝特组46例[9.6%] vs安慰剂组57例[12.3%]; p=0.19）或无既存视网膜病变患者亚组（43例[11.4%] vs 43例[11.7%]; p=0.87）之间的主要终点视网膜病变分级的2步进展无显著差异。相比之下，在既存视网膜病变患者中，非诺贝特组发生2步进展的患者明显少于安慰剂组（3例[3.1%]患者vs 14例[14.6%]; p=0.004）。非诺贝特组视网膜病变分级、黄斑水肿或激光治疗的2步进展的探索性复合终点显著低于安慰剂组（HR 0.66，95% CI 0.47-0.94; p=0.022）。解释2型糖尿病患者使用非诺贝特治疗可以减少糖尿病视网膜病变激光治疗的需要，尽管这种作用的机制似乎与脂质的血浆浓度无关。
Background laser treatment for diabetic retinopathy is often associated with visual field reduction and other ocular side-effects. Our aim was to assess whether long-term lipid-lowering therapy with fenofibrate could reduce the progression of retinopathy and the need for laser treatment in patients with type 2 diabetes mellitus.Methods The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study was a multinational randomised trial of 9795 patients aged 50-75 years with type 2 diabetes mellitus. Eligible patients were randomly assigned to receive fenofibrate 200 mg/day (n=4895) or matching placebo (n=4900). At each clinic visit, information concerning laser treatment for diabetic retinopathy-a prespecified tertiary endpoint of the main study-was gathered. Adjudication by ophthalmologists masked to treatment allocation defined instances of laser treatment for macular oedema, proliferative retinopathy, or other eye conditions. In a substudy of 1012 patients, standardised retinal photography was done and photographs graded with Early Treatment Diabetic Retinopathy Study (ETDRS) criteria to determine the cumulative incidence of diabetic retinopathy and its component lesions. Analyses were by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN64783481.Findings Laser treatment was needed more frequently in participants with poorer glycaemic or blood pressure control than in those with good control of these factors, and in those with a greater burden of clinical microvascular disease, but the need for such treatment was not affected by plasma lipid concentrations. The requirement for first laser treatment for all retinopathy was significantly lower in the fenofibrate group than in the placebo group (164 [3.4%] patients on fenofibrate vs 238 [4.9%] on placebo; hazard ratio [HR] 0.69, 95% Cl 0.56.0.84; p=0.0002; absolute risk reduction 1.5% [0.7-2.3]). In the ophthalmology substudy, the primary endpoint of 2-step progression of retinopathy grade did not differ significantly between the two groups overall (46 [9.6%] patients on fenofibrate vs 57 [12.3%] on placebo; p=0.19) or in the subset of patients without pre-existing retinopathy (43 [11.4%] vs 43 [11.7%]; p=0.87). By contrast, in patients with pre-existing retinopathy, significantly fewer patients on fenofibrate had a 2-step progression than did those on placebo (three [3.1%] patients vs 14 [14.6%]; p=0.004). An exploratory composite endpoint of 2-step progression of retinopathy grade, macular oedema, or laser treatments was significantly lower in the fenofibrate group than in the placebo group (HR 0.66, 95% CI 0.47-0.94; p=0.022).Interpretation Treatment with fenofibrate in individuals with type 2 diabetes mellitus reduces the need for laser treatment for diabetic retinopathy, although the mechanism of this effect does not seem to be related to plasma concentrations of lipids.