What does MACE (major adverse cardiac events) refer to in acute coronary syndrome?

What is MACE in Acute Coronary Syndrome?

MACE (Major Adverse Cardiac Events) in acute coronary syndrome is a composite endpoint that traditionally includes cardiac death, nonfatal myocardial infarction, and stroke, though the specific components vary significantly across clinical contexts and studies. 1

Core Components of MACE

The American College of Cardiology/American Heart Association defines MACE as including: 1

• Death (cardiac or procedure-related)
• Myocardial infarction (both ST-segment elevation MI and non-ST-segment elevation MI)
• Stroke
• Ischemia requiring emergency coronary artery bypass grafting (CABG)

In specific interventional cardiology contexts (PCI procedures), MACE may also include: 1

• Urgent target-vessel revascularization
• Vascular access site complications
• Contrast-induced nephropathy
• Excessive bleeding requiring treatment

Clinical Application in ACS Risk Stratification

The acceptable threshold for excluding ACS is defined as less than 1% risk of 30-day MACE. 2 This threshold is critical when determining which patients can be safely discharged from the emergency department versus those requiring admission and further evaluation.

Risk Stratification Framework

Clinical decision pathways use MACE as the primary outcome to stratify patients into risk categories: 2

• Low-risk patients: <1% 30-day MACE rate
• Intermediate-risk patients: 8-20% 30-day MACE rate 3
• High-risk patients: >26% 30-day MACE rate 3

Common Risk Scoring Systems

Multiple validated risk scores predict 30-day MACE in ACS patients: 2, 3

• GRACE score: Uses 8 variables (age, Killip class, systolic blood pressure, heart rate, ST-segment deviation, cardiac arrest, serum creatinine, cardiac biomarkers) with superior discriminative ability (C-statistic 0.83) 3
• HEART score: Consists of 5 components (History, ECG, Age, Risk factors, Troponin) with scores 0-3 indicating <1% MACE risk, 4-6 indicating 8-20% risk, and 7-10 indicating >26% risk 3
• TIMI score: Uses 7 equally-weighted variables to predict 14-day outcomes 3

Important Clinical Caveats

Heterogeneity in MACE Definitions

A critical limitation is that there is no standardized definition of MACE across studies, leading to substantial heterogeneity in reported outcomes. 4 Different studies include varying individual components, which can lead to markedly different results and conclusions. 4

Troponin Testing Limitations

Troponins measured at 0 and 2 hours should NOT be used alone to exclude ACS. 2 The 2015 International Consensus strongly recommends against using high-sensitivity cardiac troponin (hs-cTnT or hs-cTnI) alone measured at 0 and 2 hours to exclude the diagnosis of ACS. 2

Instead, troponin testing must be combined with clinical risk stratification: 2

• Negative hs-cTnI at 0 and 2 hours + low-risk clinical score (Vancouver rule or TIMI score 0-1) may be used to exclude ACS
• Negative cTnI or cTnT at 0 and 3-6 hours + very low-risk clinical score (TIMI score 0, low-risk HEART score, low-risk North American CP rule) may be used to exclude ACS

Impact of Prior Coronary Disease

Among moderate-risk patients, those with known coronary artery disease have a 7.1% 30-day MACE rate compared to only 1.4% in patients without prior CAD. 5 This five-fold difference emphasizes that prior CAD history substantially elevates risk even when initial troponins are negative and ECG is nonischemic. 5

Prognostic Significance

Patients with GRACE scores >140 are considered high-risk and require aggressive therapy including early invasive strategy, intensive antiplatelet therapy, and close monitoring. 3, 6 The American College of Cardiology defines elevated surgical risk as ≥1% risk of MACE, which serves as a threshold for enhanced monitoring and risk stratification. 1