Major Adverse Cardiovascular Event Definitions Used in Observational Analysis of Administrative Databases: a Systematic Review

Background: Major adverse cardiovascular events (MACE) are increasingly used as composite outcomes in randomized controlled trials (RCTs) and observational studies. However, it is unclear how observational studies most commonly define MACE in the literature when using administrative data.

Methods: We identified peer-reviewed articles published in MEDLINE and EMBASE between January 1, 2010 to October 9, 2020. Studies utilizing administrative data to assess the MACE composite outcome using International Classification of Diseases 9th or 10th Revision diagnosis codes were included. Reviews, abstracts, and studies not providing outcome code definitions were excluded. Data extracted included data source, timeframe, MACE components, code definitions, code positions, and outcome validation.

Results: A total of 920 articles were screened, 412 were retained for full-text review, and 58 were included. Only 8.6% (n = 5/58) matched the traditional three-point MACE RCT definition of acute myocardial infarction (AMI), stroke, or cardiovascular death. None matched four-point (+unstable angina) or five-point MACE (+unstable angina and heart failure). The most common MACE components were: AMI and stroke, 15.5% (n = 9/58); AMI, stroke, and all-cause death, 13.8% (n = 8/58); and AMI, stroke and cardiovascular death 8.6% (n = 5/58). Further, 67% (n = 39/58) did not validate outcomes or cite validation studies. Additionally, 70.7% (n = 41/58) did not report code positions of endpoints, 20.7% (n = 12/58) used the primary position, and 8.6% (n = 5/58) used any position.

Conclusions: Components of MACE endpoints and diagnostic codes used varied widely across observational studies. Variability in the MACE definitions used and information reported across observational studies prohibit the comparison, replication, and aggregation of findings. Studies should transparently report the administrative codes used and code positions, as well as utilize validated outcome definitions when possible.