ACCORD (Action to Control Cardiovascular Risk in Diabetes)

ACCORD（控制糖尿病心血管风险的行动）

• 批准号: 10019993
• 负责人: EMILY Y CHEW
• 金额: $ 5.51万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10019993
• 关键词: Blood Glucose; Blood Pressure; Cardiovascular Diseases; Cardiovascular system; Cataract Extraction; Cessation of life; Clinical Treatment; Confidence Intervals; Congestive Heart Failure; Coronary Arteriosclerosis; Coronary heart disease; Diabetes Mellitus; Diabetic Retinopathy; Dyslipidemias; Early treatment; Enrollment; Eye; Fenofibrate; Fundus; Fundus photography; Glycosylated hemoglobin A; Goals; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Hospitalization; LDL Cholesterol Lipoproteins; Lipids; Low-Density Lipoproteins; Masks; Measurement; Medical; Microvascular Dysfunction; Myocardial Infarction; Newly Diagnosed; Non-Insulin-Dependent Diabetes Mellitus; Odds Ratio; Ophthalmic examination and evaluation; Outcome; Outcome Measure; Participant; Patients; Persons; Phase; Placebos; Protocols documentation; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Risk; Sample Size; Schedule; Serum; Simvastatin; Stroke; Time Study; Triglycerides; Visual Acuity; blood pressure regulation; cardiovascular risk factor; clinical effect; conventional therapy; design; follow-up; glycemic control; hypertension control; mortality; posters; primary endpoint; primary outcome; recruit; secondary analysis; secondary outcome; stereoscopic; treatment arm

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) is a randomized clinical trial with 3 components, determining the effects of blood glucose lowering, blood pressure lowering, and lowering of serum triglycerides plus raising serum high density lipoprotein cholesterol levels on cardiovascular disease (CVD) in patients with type 2 diabetes. 10,000 participants will be randomly assigned in equal numbers to two glycemic management treatment arms. An intensive treatment arm will aim to achieve and maintain hemoglobin A1C level < 6.0%. A conventional treatment arm will target an A1C range of 7.0-7.9% with an expected mean value of approximately 7.5%. 4,200 of these participants will simultaneously be randomized to one of two hypertension management protocols. The intensive treatment arm targets a systolic blood pressure (SBP) < 120 mmHg and the conventional treatment arm targets a SBP <140 mmHg. 5,800 dyslipidemic ACCORD participants (HDL < 40 mg/dl) will be randomly assigned in a double masked fashion to either a placebo or fenofibrate 160 mg daily for reduction of triglyceride levels and increase in high-density lipoprotein cholesterol levels, after low-density lipoprotein cholesterol has been lowered with statin therapy (simvastatin 20 mg daily) to target LDL levels of approximately 100 mg/dl or lower. The primary endpoint of the ACCORD Trial is death from cardiovascular causes, non-fatal myocardial infarction and non-fatal stroke. Secondary outcomes include: the combination of the primary outcome plus any revascularization for coronary artery disease plus hospitalization for congestive heart failure; total mortality, cardiovascular mortality; any one of the specific coronary heart disease endpoints noted above, and fatal and non-fatal strokes. Other microvascular complications were also assessed in this study. An ancillary eye study was designed to evaluate the effects of these medical treatments on diabetic retinopathy within the ACCORD Trial. The ACCORD Eye Study consists of 2 eye exams with fundus photography of 7 stereoscopic fields, scheduled for baseline and year 4 of follow-up. The projected sample size is 4065 patients. The main ACCORD Trial, which follows the Vanguard Phase, recruited and randomizes participantss from February 2003 through June 2005. The ACCORD Eye Study showed that intensive glycemic control and intensive lipid therapy with fenofibrate and a statin reduced the risk of progression of diabetic retinopathy. At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval CI, 0.51 to 0.87; P = 0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P = 0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio: 1.23; 95% CI, 0.84 to 1.79; P = 0.29). ACCORD Eye study participants, who had baseline and year 4 eye exams and fundus photograph, were re-examined in the ACCORD Follow-on (ACCORDION) Eye Study (2010-2014) 4 years following ACCORD trial closeout. The outcome measure was diabetic retinopathy progression of 3 steps on the Early Treatment Diabetic Retinopathy Study scale. Results: Diabetic retinopathy progressed in 5.8% with intensive glycemic treatment versus 12.7% with standard (adjusted odds ratio (aOR): 0.42, 95% confidence interval CI: 0.28 to 0.63, P<0.0001); 7.5% with intensive BP treatment versus 6.0% for standard (aOR: 1.21, 95% CI: 0.61 to 2.40, P=0.59); and 11.8% with fenofibrate versus 10.2% with placebo (aOR: 1.13, 95% CI: 0.71 to 1.79, P=0.60) in ACCORDION Eye participants (n=1310). Conclusions: Prior intensive glycemic control continued to reduce diabetic retinopathy progression, despite similar A1C levels when ACCORD Study ended.This persistence of benefits of glycemic control is demonstrated for the first time study in persons with type 2 diabetes of 10 years duration and established cardiovascular disease, unlike the newly diagnosed participants of UKPDS, that demonstrated this effect. The benefit of fenofibrate, however, did not persist. Intensive BP control had no effect.

控制糖尿病心血管风险的行动（雅阁）是一项随机临床试验，包括3个组成部分，旨在确定降低血糖、降低血压、降低血清甘油三酯和升高血清高密度脂蛋白胆固醇水平对2型糖尿病患者心血管疾病（CVD）的影响。10，000名参与者将被随机分配到两个血糖管理治疗组。强化治疗组的目标是实现并维持血红蛋白A1 C水平<6.0%。常规治疗组的目标A1 C范围为7.0-7.9%，预期平均值约为7.5%。 其中4,200名参与者将同时随机接受两种高血压管理方案之一。强化治疗组的目标是收缩压（SBP）< 120 mmHg，常规治疗组的目标是SBP <140 mmHg。 5，800名血脂异常雅阁参与者（HDL < 40 mg/dl）将以双盲方式随机分配至安慰剂或非诺贝特160 mg/天，用于降低甘油三酯水平和增加高密度脂蛋白胆固醇水平，他汀类药物治疗降低低密度脂蛋白胆固醇后（辛伐他汀20 mg/天）至约100 mg/dl或更低的目标LDL水平。 雅阁试验的主要终点是心血管原因导致的死亡、非致死性心肌梗死和非致死性卒中。次要结局包括：主要结局加上冠状动脉疾病的任何血运重建加上充血性心力衰竭的住院治疗的组合;总死亡率、心血管死亡率;上述任何一种特定的冠状动脉心脏病终点，以及致命性和非致命性中风。本研究还评估了其他微血管并发症。设计了一项辅助眼部研究，以评价雅阁试验中这些药物治疗对糖尿病视网膜病变的影响。 雅阁眼科研究包括2次眼科检查，包括7个立体视野的眼底摄影，计划在基线和第4年随访时进行。预计样本量为4065例患者。主要的雅阁试验遵循先锋阶段，从2003年2月至2005年6月招募并随机分配参与者。雅阁眼科研究表明，强化血糖控制和非诺贝特和他汀类药物强化脂质治疗可降低糖尿病视网膜病变进展的风险。 4年时，强化治疗组的糖尿病视网膜病变进展率为7.3%，而标准治疗组为10.4%（校正比值比为0.67; 95%置信区间CI，0.51 - 0.87; P = 0.003）;非诺贝特强化治疗6.5% 血脂异常治疗组为10.2%，安慰剂组为10.2%（校正比值比：0.60; 95%CI：0.42 - 0.87; P = 0.006）;强化降压治疗组为10.4%，标准治疗组为8.8%（校正比值比：1.23; 95%CI：0.84 - 1.79; P = 0.29）。 在ACCORD试验结束后4年，在ACCORD随访（ACCORDION）眼科研究（2010-2014）中对接受基线和第4年眼科检查和眼底照片的ACCORD眼科研究参与者进行了重新检查。 结果测量是糖尿病视网膜病变早期治疗研究量表上的3级糖尿病视网膜病变进展。 结果如下：糖尿病视网膜病变进展，强化血糖治疗组为5.8%，标准血糖治疗组为12.7%。（校正比值比（aOR）：0.42，95%置信区间CI：0.28 - 0.63，P<0.0001）;强化BP治疗组为7.5%，标准BP治疗组为6.0%（aOR：1.21，95% CI：0.61 - 2.40，P=0.59）;在ACCORDION Eye受试者（n=1310）中，非诺贝特组为11.8%，安慰剂组为10.2%（aOR：1.13，95% CI：0.71 - 1.79，P=0.60）。 结论：先前的强化血糖控制继续减少糖尿病视网膜病变的进展，尽管类似的A1 C水平时，雅阁研究结束。这种持续的血糖控制的好处是证明了第一次研究的2型糖尿病患者的10年的时间和确定的心血管疾病，不像新诊断的参与者UKPDS，证明了这种效果。 然而，非诺贝特的益处并未持续。 强化血压控制没有效果。