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; 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.

控制糖尿病中心血管风险（ACCE）的动作是一项随机临床试验，具有3个成分，确定了血糖降低，血压降低以及降低血清甘油三酸酯的影响以及血清高密度脂蛋白胆固醇水平对心血管疾病（CVD）的影响。 10,000名参与者将以同等数量的随机分配，而两个血糖管理治疗组。密集的治疗组将旨在实现和维持血红蛋白A1C水平<6.0％。常规治疗组的目标范围为7.0-7.9％，预期平均值约为7.5％。 这些参与者中有4,200名将同时将其随机分为两个高血压管理方案之一。强化治疗组的靶向收缩压（SBP）<120 mmHg，常规治疗组的靶向SBP <140 mmHg。 5,800名血脂型协定参与者（HDL <40 mg/dl）将以双掩盖方式随机分配给安慰剂或fenofibrate每天160 mg，以降低甘油三酸酯水平，并在高密度脂蛋白胆固醇后（抑制了磷酸脂蛋白胆固醇）的高密度脂蛋白胆固醇水平降低甘油三酸酯水平，并降低了他的素胆固醇。大约100 mg/dl或更低的水平。 协议试验的主要终点是死于心血管原因，非致命性心肌梗塞和非致命性中风。次要结果包括：主要结局以及冠状动脉疾病的任何血运重建以及用于充血性心力衰竭的住院；总死亡率，心血管死亡率；上述特定的冠心病终点中的任何一个，以及致命的和非致命的中风。在本研究中还评估了其他微血管并发症。一项辅助眼研究旨在评估这些药物治疗对统一试验中糖尿病性视网膜病的影响。 Accord Eye研究由2次眼科检查和7个立体田地的眼底摄影组成，该摄影计划用于后续的基线和后续第4年。预计样本量为4065例。在Vanguard阶段之后的主要协议试验从2003年2月到2005年6月招募并随机招募了参与者。协定眼研究表明，密集的血糖控制和强化脂质疗法具有非诺贝特，而他汀类药物降低了糖尿病性视网膜病的进展的风险。 在4年时，强烈的血糖治疗的糖尿病性视网膜病变率为7.3％，而标准治疗率为10.4％（调整后的优势比，0.67； 95％置信区间CI，0.51至0.87； p = 0.003）; 6.5％的非诺贝特型 血脂血症治疗，安慰剂（调整后比值比，0.60; 95％CI，0.42至0.87; p = 0.006）的血脂异常疗法； p = 0.006）；和10.4％的血压疗法为10.4％，而标准治疗的8.8％（调整后的比率：1.23; 95％CI，0.84至1.79; p = 0.29）。 Accord Eye研究参与者的基线和4年级的眼科检查和眼底照片，在Accord Accord试验结束后的4年后，在Accord后续（Accipion）眼睛研究（2010-2014）中重新审查。 结果度量是早期治疗糖尿病性视网膜病研究量表上3个步骤的糖尿病性视网膜病变进展。 结果：糖尿病性视网膜病在5.8％的情况下以强烈的血糖治疗为5.8％，而标准性（调整后的比值比（AOR）：0.42，95％置信区间CI：0.28至0.63，p <0.0001）的糖尿病性病变率为12.7％。 7.5％的BP治疗为7.5％，标准为6.0％（AOR：1.21，95％CI：0.61至2.40，p = 0.59）;和安慰剂（AOR：1.13，95％CI：0.71至1.79，p = 0.60）中，具有非诺佛甲酸酯为10.8％，而10.2％（n = 1310）。 结论：尽管Accor研究结束时A1C水平相似，但先前的强化血糖控制仍继续降低糖尿病性视网膜病的进展。在第一次进行10年型糖尿病患者的血糖控制的持久性是在10年型糖尿病患者中的首次研究，并且与新诊断的UKP参与者相比，这一持续的持续时间为10年的持续时间，并确定了这一效果。 但是，非诺贝特的好处并没有持续存在。 密集的BP控制无效。