The problem with composite end points in cardiovascular studies: the story of major adverse cardiac events and percutaneous coronary intervention.
OBJECTIVE
Our purpose was to evaluate the heterogeneity and validity of composite end points, major adverse cardiac events (MACE) in particular, in cardiology research.


BACKGROUND
The term MACE is a commonly used end point for cardiovascular research. By definition, MACE is a composite of clinical events and usually includes end points reflecting safety and effectiveness. There is no standard definition for MACE, as individual outcomes used to make this composite end point vary by study. This inconsistency calls into question whether use of MACE in cardiology research is of value.


METHODS
We conducted a 2-phase literature review on the use of MACE as a composite end point: 1) studies that have compared use of bare-metal versus drug-eluting stents; and 2) studies published in the Journal in calendar year 2006. We subsequently tested 3 different definitions of MACE during 1-year of follow-up among 6,922 patients in the DEScover registry who received at least 1 drug-eluting stent.


RESULTS
The review identified substantial heterogeneity in the study-specific individual outcomes used to define MACE. Markedly different results were observed for selected patient subsets of acute myocardial infarction (MI) (vs. no MI) and multilesion stenting (vs. single-lesion stenting) according to the various definitions of MACE.


CONCLUSIONS
Varying definitions of composite end points, such as MACE, can lead to substantially different results and conclusions. Therefore, the term MACE, in particular, should not be used, and when composite study end points are desired, researchers should focus separately on safety and effectiveness outcomes, and construct separate composite end points to match these different clinical goals.
Kip
Kevin E
KE
College of Nursing, University of South Florida, Tampa, Florida 33612, USA. kkip@health.usf.edu
Hollabaugh
Kim
K
Marroquin
Oscar C
OC
Williams
David O
DO
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D003327:Coronary Disease / Q000401:mortality / Q000628:therapy*; D054855:Drug-Eluting Stents / Q000009:adverse effects; D023381:Endpoint Determination / Q000379:methods* / Q000592:standards; D006801:Humans; D009203:Myocardial Infarction / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control; D017063:Outcome Assessment, Health Care; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D015607:Stents / Q000009:adverse effects; D009626:Terminology as Topic