Effects of combination lipid therapy in type 2 diabetes mellitus.
Effects of combination lipid therapy in type 2 diabetes mellitus.
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DOI：
10.1056/nejmoa1001282
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发表时间：
2010-04-29
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影响因子：
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通讯作者：
Byington RP
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作者：
ACCORD Study Group;Ginsberg HN;Elam MB;Lovato LC;Crouse JR 3rd;Leiter LA;Linz P;Friedewald WT;Buse JB;Gerstein HC;Probstfield J;Grimm RH;Ismail-Beigi F;Bigger JT;Goff DC Jr;Cushman WC;Simons-Morton DG;Byington RP
我们研究了与他汀类药物单药治疗相比，他汀类药物加贝特类药物联合治疗是否会降低心血管疾病高危的2型糖尿病患者的心血管疾病风险。我们将5518名正在接受开放标签辛伐他汀治疗的2型糖尿病患者随机分为两组，一组接受非诺贝特治疗，另一组接受安慰剂治疗。主要结局是首次发生非致死性心肌梗死、非致死性卒中或心血管原因死亡。平均随访4.7年。非诺贝特组主要结局的年发生率为2.2%，安慰剂组为2.4%（非诺贝特组的风险比为0.92; 95%可信区间[CI]为0.79 - 1.08; P = 0.32）。两个研究组在任何次要结局方面也没有显著差异。非诺贝特组的年死亡率为1.5%，安慰剂组为1.6%（风险比，0.91; 95%CI，0.75 - 1.10; P = 0.33）。预先规定的亚组分析表明，根据性别，治疗效果存在异质性，男性获益，女性可能受损（相互作用P = 0.01），根据脂质亚组，可能存在相互作用，基线甘油三酯水平高和基线高密度脂蛋白胆固醇水平低的患者可能获益（相互作用P = 0.057）。与辛伐他汀单药相比，非诺贝特和辛伐他汀联合用药不能降低致死性心血管事件、非致死性心肌梗死或非致死性卒中的发生率。这些结果不支持常规使用非诺贝特和辛伐他汀联合治疗来降低大多数2型糖尿病高危患者的心血管风险。（ClinicalTrials.gov编号，NCT 00000620。）
We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease. We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years. The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P = 0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P = 0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P = 0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P = 0.057 for interaction). The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)