MACE: Clinical implications and recommendations for cardiac care

By Naveed Saleh, MD, MS
Published February 3, 2022

Key Takeaways

  • Major adverse cardiac events (MACE) refers to non-fatal stroke, non-fatal myocardial infarction, or cardiovascular death.

  • MACE is important for all physicians to recognize and predict.

  • MACE can be problematic and warrant close follow-up even in those without severe coronary artery disease.

Physicians regularly encounter patients with histories of heart disease, but heart disease may be one component of a constellation of conditions and/or cardiac events. This constellation has a name: major adverse cardiac events (MACE). MACE predisposes people to future disease and death, making it essential knowledge for anyone treating cardiac patients.

Defining and preventing MACE can be tricky, and those at risk require follow-up.

Explaining MACE

MACE refers to endpoints including non-fatal stroke, non-fatal myocardial infarction, or cardiovascular death. Its definition, however, remains somewhat amorphous.

“Over time various definitions have been used in cardiovascular research with MACE selected as primary or secondary end-point,” authors of a Cureus review wrote. “It has been defined by various authors since mid-1990 to include an overlapping range of adverse events.”

Those adverse events include heart failure, angina pain that recurs, non-fatal re-infarction, hospital readmission for cardiovascular-related illness, repeat percutaneous coronary intervention (PCI), coronary artery bypass grafting, and all-cause mortality, as well as unscheduled coronary revascularization, re-infarction, and stroke.

The authors found that the incidence of MACE is between 4.2% and 51% in those who had an ST-elevation myocardial infarction  (STEMI) regardless of the mode of treatment. Follow-up visits for MACE following STEMI can occur from the first day to 10 years. 

Related: ​​What makes a community-based health center for cardio treatment successful?

Clinical implications

As mentioned, coronary artery disease (CAD) is linked to MACE. In a 2019 study published in the Journal of the American Heart Association, Korean researchers assessed the link between CAD and MACE for a duration of up to 5 years in 5,890 patients who had chest pain without severe CAD.

The researchers found that in this sample, coronary artery spasm (CAS), myocardial bridge (MB), or insignificant coronary stenosis (ICS) were common. Moreover, in those without severe CAD, aging and ICS were strongly linked to future long-term MACE. On a related note, dyslipidemia, ICS, myocardial bridge, and CAS strongly predicted angina pectoris.

During follow-up, fewer than 1% of patients experienced stroke or heart failure.

Clinical recommendations

Based on results of the current study, researchers suggested certain clinical recommendations. First, chest pain could be deduced as cardiogenic if CAS, MB, and ICB are present—even if severe CAD Is not present. Furthermore, CAS, MB, and ICS can appear alone or in combination, but the combination is linked to poor long-term clinical outcomes compared with single factors. Even in those without severe CAD, ICS was the strongest independent predictor of MACE. When observed with ICS, MACE requires close follow-up.

Regarding choice stent placement for percutaneous coronary intervention (PCI), drug-eluted stents may better protect against MACE endpoints including target vessel revascularization and hospital readmission compared with bare-metal stents. This 2018 cross-sectional study was performed by Iranian researchers and involved 192 patients, of whom 93.8% received stents.

Related: The brain-heart connection holds important lessons for clinicians

MACE after noncardiac surgery

In patients receiving noncardiac surgical procedures, MACE are common, according to the author of Essentials of Cardiac Anesthesia for Noncardiac Surgery. Although the occurrence of perioperative myocardial infarction (PMI) is less than 1%, many more patients experience a perioperative increase in cardiac troponins without other criteria for myocardial infarction, which is referred to as myocardial injury after noncardiac surgery (MINS).

In surgical patients, physicians should watch for MACE risk factors. These risk factors can be patient specific or surgery specific. Patient-specific factors include advanced age, kidney disease, and anemia. Surgery-specific factors include type of procedure, urgency, complexity, and intraoperative complications.

Of note, there are scoring systems that allow specialists to predict MACE preoperatively (e.g., Revised Cardiac Risk Index) and intraoperatively (e.g., ANESCARDIOCAT). These tests can help identify which patients need preventive measures and strict intraoperative/postoperative monitoring.

What does this mean to you?

MACE can take many presentations in your patients. It can be defined as non-fatal stroke, non-fatal myocardial infarction or cardiovascular death. Keep an eye out for those at risk and mitigate this risk as appropriate via follow-up referral. Even in those without severe CAD, MACE can be problematic and demands follow-up.


  1. Choi BJ. Association of Major Adverse Cardiac Events up to 5 Years in Patients With Chest Pain Without Significant Coronary Artery Disease in the Korean Population. JAHA.

  2. Farshidi H. Major adverse cardiovascular event (MACE) after percutaneous coronary intervention in one-year follow-up study. Electronic Physician.

  3. Poudel I. Major Adverse Cardiovascular Events: An Inevitable Outcome of ST-elevation myocardial infarction? A Literature Review. Cureus.

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