What is the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial?

From the Guidelines

The ACCORD trial was a major clinical study that examined intensive versus standard blood glucose control in patients with type 2 diabetes who were at high risk for cardiovascular events, and it was stopped early due to increased mortality in the intensive therapy group, leading to a recommendation of individualizing HbA1c targets with less stringent goals for high-risk patients 1.

Key Findings

• The ACCORD trial was stopped early after finding that intensive glucose control (targeting HbA1c below 6.0%) increased mortality compared to standard treatment (targeting HbA1c 7.0-7.9%) 1.
• Patients in the intensive therapy group had a 22% higher relative risk of death, with the intensive treatment involving multiple medications including insulin, metformin, sulfonylureas, and thiazolidinediones to achieve tight glucose control 1.
• The standard treatment group used similar medications but with less aggressive dosing and targets, and the trial significantly changed diabetes management by demonstrating that very tight glucose control in high-risk patients with longstanding diabetes may be harmful rather than beneficial 1.

Implications

• The mechanisms behind this increased mortality remain unclear but may involve hypoglycemia, rapid glucose lowering, or medication side effects 1.
• Based on ACCORD findings, current diabetes guidelines recommend individualizing HbA1c targets, with less stringent goals (around 7-8%) for patients with established cardiovascular disease, longer diabetes duration, or history of severe hypoglycemia 1.
• The trial's results emphasize the importance of considering the individual patient's risk factors and medical history when determining the optimal HbA1c target, rather than adopting a one-size-fits-all approach 1.

From the Research

Overview of the ACCORD Trial

• The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial is a randomized, multicenter, double 2 x 2 factorial design study involving 10,251 middle-aged and older participants with type 2 diabetes who are at high risk for cardiovascular disease (CVD) events 2.
• The trial aims to test the effects of intensive control of glycemia and other CVD risk factors on CVD event rates in patients with type 2 diabetes 3, 2.

Objectives and Design

• The ACCORD trial has three main objectives: to test the hypothesis that a therapeutic strategy targeting a glycosylated hemoglobin (HbA1c) level of <6.0% will reduce the rate of CVD events more than a strategy targeting an HbA1c level of 7.0%-7.9% 2.
• The trial also tests the hypothesis that a therapeutic strategy using a fibrate to increase high-density lipoprotein cholesterol and lower triglyceride levels, together with a statin to lower low-density lipoprotein cholesterol, will reduce the rate of CVD events compared with a strategy using a statin plus a placebo 2.
• Additionally, the trial tests the hypothesis that a therapeutic strategy targeting a systolic blood pressure of <120 mm Hg will reduce the rate of CVD events compared with a strategy targeting a systolic blood pressure of <140 mm Hg 2.

Findings and Results

• The ACCORD trial found that intensive glucose-lowering (with a hemoglobin A1c target of less than 6.0%) did not reduce the incidence of atherosclerotic disease events and death compared with standard treatment (with a hemoglobin A1c target of 7.0% to 7.9%) in patients with type 2 diabetes at high risk of cardiovascular events 4.
• However, a post-hoc analysis of the ACCORD trial data found that some patient subgroups may benefit from intensive glycaemic and blood pressure control, including those with baseline HbA1c <8.5% and those with estimated glomerular filtration rate ≥106 ml/min/1.73 m2 5.
• Another study using machine learning analysis found that intensive glycemic control was associated with lower major adverse cardiovascular events (MACE) in subgroups with low, intermediate, and high MACE rates 6.