MACE (Major Adverse Cardiovascular Events)

MACE stands for Major Adverse Cardiovascular Events. It is the composite endpoint cardiovascular outcome trials are built around, and in this field it almost always means three things counted together: death from cardiovascular causes, non-fatal heart attack, and non-fatal stroke. Trials count the first of these to occur in each participant.

Composites exist for a practical reason. Individual events are rare enough that a trial powered to detect a change in heart attacks alone would need to be enormous. Bundling related outcomes makes the question answerable at a feasible size — at the cost of some precision, because a reduction in the composite does not tell you which component moved.

Three trials define what GLP-1 drugs do to MACE. LEADER followed 9,340 people with type 2 diabetes on liraglutide: the primary outcome occurred in 13.0% versus 14.9% on placebo, a hazard ratio of 0.87, with cardiovascular death down to 4.7% from 6.0%. SUSTAIN-6 tested semaglutide in type 2 diabetes and found the composite in 6.6% versus 8.9% (hazard ratio 0.74). SELECT extended the question to 17,604 people with heart disease and excess weight but no diabetes, finding 6.5% versus 8.0% (hazard ratio 0.80).

The confusion worth naming is between relative and absolute. A 20% relative reduction sounds transformative; in SELECT the absolute difference was 1.5 percentage points over nearly four years. Both numbers are true, and the second one is the one that describes your odds.

Where this becomes practical is coverage. A cardiovascular indication on a label is a different conversation with an insurer than a weight indication. If you have documented heart disease, make sure it is in the chart before a prior authorization goes in. Our SELECT analysis and secondary endpoint deep dive break the components apart.