What is MACE (Major Adverse Cardiovascular Events)?
MACE is a composite endpoint measuring serious cardiovascular outcomes, traditionally defined as cardiac death (including fatal myocardial infarction), nonfatal myocardial infarction (both ST-segment elevation and non-ST-segment elevation MI), and stroke, though the specific components vary significantly across clinical contexts and studies. 1
Core Components
The standard definition includes three primary components (3-point MACE) 1:
- Cardiac death - including fatal myocardial infarction and death from cardiovascular causes 1
- Nonfatal myocardial infarction - encompassing both ST-segment elevation MI and non-ST-segment elevation MI 1
- Stroke - fatal and nonfatal cerebrovascular events 1
Extended Definitions
The definition of MACE is not standardized and varies substantially across studies and clinical contexts, which creates significant challenges in comparing research findings. 2, 3
Four-Point MACE
Adds unstable angina requiring coronary revascularization to the three core components 1
Five-Point MACE (Extended MACE)
May additionally include 1:
- Hospitalization for heart failure 1
- Repeat revascularization procedures (PCI or CABG) 1
- Cardiac arrest 1
Context-Specific Variations
In interventional cardiology (PCI procedures), MACE definitions often include procedure-related complications 1:
- Death related to the procedure 1
- Myocardial infarction related to the procedure 1
- Ischemia requiring emergency CABG 1
- Same-day or same-stay CABG surgery 1
In diabetes and chronic kidney disease management, MACE may be defined as a composite including myocardial infarction, stroke, and cardiovascular death (3-point MACE), with or without the addition of hospitalization for unstable angina (4-point MACE). 1
Clinical Risk Thresholds
The American Heart Association defines elevated surgical risk as ≥1% risk of MACE, which serves as a threshold for identifying patients requiring enhanced monitoring and risk stratification. 4
- Patients with Revised Cardiac Risk Index (RCRI) score ≥3 have substantially elevated MACE risk requiring aggressive intervention 4, 5
- High-risk acute coronary syndrome patients (GRACE score >140 or HEART score ≥7) require immediate intervention strategies 5
Critical Limitations and Pitfalls
The lack of standardization in MACE definitions across studies creates major problems for research interpretation and clinical application. 2, 3
Key Issues to Recognize:
- Only 8.6% of observational studies using administrative data match the traditional three-point MACE definition used in randomized controlled trials 3
- 67% of studies do not validate MACE outcomes or cite validation studies 3
- Individual outcomes used to define MACE vary substantially by study, making cross-study comparisons unreliable 2, 3
- The term "MACE" alone should not be used without specifying exact component definitions 2
Common Variations in Research:
The most frequently used MACE definitions in observational studies are 3:
- AMI and stroke only (15.5% of studies)
- AMI, stroke, and all-cause death (13.8% of studies)
- AMI, stroke, and cardiovascular death (8.6% of studies)
When evaluating research or clinical guidelines citing MACE, always verify the specific component endpoints included, as markedly different results can occur depending on the definition used. 2
Prognostic Significance
MACE serves as a critical outcome measure across cardiovascular medicine, with the presence and extent of coronary artery disease demonstrating a dose-response relationship with MACE risk. 4
- Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) have a 62.3% increased risk of developing MACE 6
- Survivors of immune-mediated thrombotic thrombocytopenic purpura experience MACE rates of 28.6% over median 7.6-year follow-up, occurring at younger ages than the general population 7
- Patients with myocardial injury and type 2 MI have higher MACE risk than those with type 1 MI, largely due to death and heart failure hospitalizations 8