What is MACE (Major Adverse Cardiac Events)?
MACE is a composite endpoint used to measure serious cardiovascular outcomes, traditionally defined as cardiac death (including fatal myocardial infarction), nonfatal myocardial infarction, and stroke, though the specific components vary significantly across clinical contexts and studies. 1
Core Components and Definitions
The traditional definition of MACE includes three primary components 1:
- Cardiac death (including fatal myocardial infarction)
- Nonfatal myocardial infarction (both ST-segment elevation MI and non-ST-segment elevation MI)
- Unstable angina requiring coronary revascularization
However, the American College of Cardiology/American Heart Association guidelines expand this to include major adverse cardiac and cerebral events (MACCE), which encompasses 1:
- Death related to the procedure or cardiac cause
- Stroke
- Myocardial infarction
- Ischemia requiring emergency coronary artery bypass grafting (CABG)
Important Variability in Clinical Practice
A critical caveat: there is no standardized definition of MACE across clinical trials and observational studies. 1, 2 Research demonstrates that only 8.6% of observational studies match the traditional three-point MACE definition, with most studies using varying combinations of endpoints 2. This heterogeneity makes direct comparison across studies challenging and limits the ability to replicate or aggregate findings 2.
Common variations include 1, 2:
- Three-point MACE: AMI, stroke, cardiovascular death
- Four-point MACE: Adding unstable angina to the above
- Five-point MACE: Adding heart failure hospitalization
- Some definitions use all-cause mortality instead of cardiovascular death 2
Clinical Context and Risk Thresholds
In the perioperative setting, the American Heart Association defines elevated surgical risk as ≥1% risk of MACE, which is used as a threshold to identify patients requiring enhanced monitoring and risk stratification 1. Patients with a Revised Cardiac Risk Index (RCRI) score ≥3 have a predicted 40.2% incidence of MACE, including myocardial injury after noncardiac surgery (MINS), myocardial infarction, cardiac arrest, or cardiac death 3.
Additional Components in Specific Contexts
In interventional cardiology procedures (PCI), complications may be categorized into eight outcome categories, with the first four considered MACCE 1:
- Death related to the procedure
- Stroke
- Myocardial infarction related to the procedure
- Ischemia requiring emergency CABG
- Vascular access site complications
- Contrast agent nephropathy
- Excessive bleeding requiring treatment
- Other complications (coronary perforation, tamponade)
Prognostic Significance
MACE rates vary substantially based on clinical presentation and patient characteristics 4, 5:
- In STEMI patients, MACE incidence ranges from 4.2% to 51% depending on treatment and follow-up duration 4
- In moderate-risk chest pain patients without prior coronary disease, 30-day MACE occurs in 1.4%, compared to 7.1% in those with known coronary artery disease 5
- The presence and extent of coronary artery disease on CT angiography demonstrates a dose-response relationship with MACE risk, with obstructive disease conferring an 11-fold increased hazard compared to normal coronary arteries 6