What is Major Adverse Cardiovascular Event (MACE) in the context of diabetes?

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Last updated: February 12, 2025View editorial policy

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From the Guidelines

Major Adverse Cardiovascular Event (MACE) in the context of diabetes refers to a composite of cardiovascular death, myocardial infarction, or stroke.

Definition of MACE

  • MACE is a composite outcome that includes:
    • Cardiovascular death
    • Myocardial infarction (non-fatal)
    • Stroke (non-fatal)
  • In some trials, a 4-point MACE is used, which also includes hospitalization for unstable angina 1.

Importance of MACE in Diabetes Management

  • MACE is a critical outcome in the management of diabetes, particularly in patients with established atherosclerotic cardiovascular disease (ASCVD) or those at high risk for ASCVD.
  • Several studies have demonstrated the effectiveness of certain medications, such as SGLT2 inhibitors and GLP-1 receptor agonists, in reducing the risk of MACE in patients with type 2 diabetes 1.

Examples of MACE Reduction with Medications

  • Empagliflozin, an SGLT2 inhibitor, has been shown to decrease the risk of MACE in patients with established ASCVD 1.
  • Liraglutide, a GLP-1 receptor agonist, has been shown to reduce the risk of MACE by 13% compared to placebo in the LEADER trial 1.
  • Dulaglutide, another GLP-1 receptor agonist, has been shown to reduce the risk of MACE by 12% compared to placebo in a recent trial 1.

From the Research

Definition of Major Adverse Cardiovascular Event (MACE)

  • MACE is a composite endpoint used to measure cardiovascular outcomes in clinical trials, particularly in the context of diabetes 2, 3, 4, 5, 6.
  • The traditional definition of MACE includes nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular death 3.
  • Some studies also include hospitalization for unstable angina (HUA) as a component of MACE, referred to as 4P-MACE 3.
  • More recently, hospitalization for heart failure (HHF) has been added to the definition of MACE, resulting in 5P-MACE 2.

Components of MACE

  • Nonfatal MI: a heart attack that does not result in death 3, 4, 5, 6.
  • Nonfatal stroke: a stroke that does not result in death 3, 4, 5, 6.
  • Cardiovascular death: death due to cardiovascular causes 3, 4, 5, 6.
  • Unstable angina: a condition characterized by chest pain or discomfort due to reduced blood flow to the heart 3.
  • Hospitalization for heart failure: hospitalization due to heart failure, which can be a complication of diabetes and cardiovascular disease 2.

Importance of MACE in Diabetes

  • Diabetes is a major risk factor for cardiovascular disease, and MACE is a common outcome in patients with diabetes 2, 3, 4, 5, 6.
  • Reducing the risk of MACE is a key goal of treatment in patients with diabetes, and can be achieved through lifestyle modifications, glucose-lowering medications, and other interventions 5, 6.
  • MACE can be used as a surrogate endpoint for cardiovascular mortality, allowing for the evaluation of treatment effects on cardiovascular outcomes in clinical trials 2.

Expansion of MACE to Include Peripheral Artery Disease (PAD)

  • PAD is a common complication of diabetes, and can contribute to significant morbidity and mortality 2.
  • Including PAD in the definition of MACE can provide a more comprehensive assessment of cardiovascular risk in patients with diabetes 2.
  • PAD outcomes, such as lower extremity amputation, can be objectively measured and improved with treatment, including intensive glycemic control and novel oral anticoagulants 2.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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