MACE Endpoint Specification Checklist
A checklist for specifying major adverse cardiovascular event composites in RWE, including component list, death source, event-date rules, validation, and component reporting.
What it is
- This guideline is the checklist layer for major adverse cardiovascular event composites in RWE. The companion MACE concept explains the endpoint family; this guideline states what must be specified when a study uses MACE, MACCE, or an expanded cardiovascular composite. It treats "MACE" as an under-specified shorthand until the component list, event-date hierarchy, death source, validation evidence, and first-event/recurrent-event rules are written down.
When to use
- Use it for cardiovascular safety or effectiveness analyses in claims, EHR, registry, linked mortality, pragmatic trial, or post-marketing safety studies whenever the endpoint is a composite of cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, heart failure, revascularization, or similar events. Use it before code-list development and table shells, because a 3-point MACE, 4-point MACE, 5-point MACE, and MACCE can answer different clinical questions and produce different effect estimates.
What it requires / checklist domains
- Name the exact variant and list every component in the protocol, SAP, code appendix, table shell, and manuscript. State whether death is cardiovascular death, all-cause death, unknown-cause death, a competing event, or a separate endpoint. Specify event-date hierarchy, same-day ties, transfer collapse, de-duplication windows, first-event versus recurrent-event handling, and whether a component closes follow-up for the composite. Provide ICD/CPT/HCPCS/death-source algorithms with diagnosis position and care-setting restrictions. Report validation metrics or validation citations for each component, not only the composite. Tabulate component-specific event counts and component-specific estimates.
When NOT to use - limitations and common misapplications
- Do not use "MACE" without a component list. Do not assume all components have the same clinical importance, ascertainment quality, or direction of treatment effect. Do not let a frequent, less severe, or poorly validated component dominate the composite without component-specific reporting. Do not combine all-cause death with nonfatal CV events without explaining the estimand and competing-risk implications. Do not borrow trial endpoint definitions into claims without a computable phenotype and validation plan. A composite can improve power, but it can also obscure heterogeneity and misclassification.
How it maps to this catalog
- This guideline cross-references `major-adverse-cardiovascular-events-mace-rwe` for the endpoint concept, `composite-endpoint-construction-rwe` for first-component and interpretation rules, `outcome-algorithm-construction-rwe` and `claims-outcome-algorithm-ppv-sensitivity-rwe` for validation, `mortality-source-hierarchy-rwe` for death source choice, `acute-event-deduplication-window-rwe` and `hospitalization-transfer-collapse-rwe` for event construction, and `competing-risks-cause-specific-fine-gray-rwe` when death and nonfatal events need separate causal interpretation.
Checklist
- Name the MACE variant and list every component in the protocol, SAP, table shell, and manuscript.
- State whether death is cardiovascular death, all-cause death, unknown-cause death, a competing event, or a separate endpoint.
- Specify event-date hierarchy, first-event versus recurrent-event handling, same-day ties, transfers, and de-duplication windows.
- Provide ICD/CPT/HCPCS/death-source algorithms with diagnosis position and care-setting restrictions.
- Report validation metrics or validation citations for each component, not only the composite.
- Tabulate component-specific event counts and component-specific estimates alongside the composite.
- Run sensitivity analyses that remove low-specificity or high-frequency components if they dominate the composite.