Major adverse cardiovascular events

Major adverse cardiovascular events (MACE, or major adverse cardiac events) is a composite endpoint frequently used in cardiovascular research.^[1][2] Despite widespread use of the term in clinical trials, the definitions of MACE can differ, which makes comparison of similar studies difficult.^[3]

The so-called "classical 3-point MACE" is defined as a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death.^[4][5] Another study similarly defined MACE as a composite of nonfatal stroke, nonfatal acute coronary syndrome, and death from vascular causes.^[6] But another study defines MACE as "CVD events, admission for HF (heart failure), ischemic cardiovascular [CV] events, cardiac death".^[7] Yet another study defined MACE as "CV death, hospitalization for HF, or myocardial infarction (MI)".^[8]

The heterogeneity of the sets defining MACE, hampering systematic reviews and meta-analyses, has been repeatedly criticized.^[9][10][11]

Which conditions are risk factors for MACE depends on some characteristics of the investigated cohort. Established risk indicators in the general population include age, pre-existing cardiovascular disease, smoking, diabetes mellitus, elevated concentrations of triglycerides and non-HDL cholesterol concentration, reduced HDL concentration and hypertension, as, e. g., demonstrated by the Framingham Heart Study. More recently, additional risk indicators have been identified, e. g. type 2 allostatic load,^[12] high-sensitivity C-reactive protein, d-dimer level,^[13] renal failure,^[14] consumption of salt as sodium chloride,^[6] and altered thyroid function.^{[15][16][17][18]}

Two reviews have concluded that SGLT2 inhibitors benefit patients with atherosclerotic MACE.^[19][20] One of those studies defined MACE as the composite of myocardial infarction, stroke, or cardiovascular death.^[19] Other studies have shown MACE to be potently predicted by levels of ceramide found in patients.^[21]