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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

The Problem With Composite End Points in Cardiovascular Studies

The Story of Major Adverse Cardiac Events and Percutaneous Coronary Intervention

Kevin E. Kip, PhD^_*,_*, Kim Hollabaugh, RN, MSN, Oscar C. Marroquin, MD, FACC and David O. Williams, MD, FACC

^_* College of Nursing, University of South Florida, Tampa, Florida
School of Nursing, University of Pittsburgh, Pittsburgh, Pennsylvania
Cardiovascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania
Department of Cardiology, Rhode Island Hospital, Providence, Rhode Island.

Manuscript received May 2, 2007; revised manuscript received September 4, 2007, accepted October 29, 2007.

^_* Reprint requests and correspondence: Dr. Kevin E. Kip, University of South Florida, College of Nursing, MDC 22, Room 2010, 12901 Bruce B. Downs Boulevard, Tampa, Florida 33612. (Email: kkip{at}health.usf.edu).

Objectives: 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.

Abbreviations and Acronyms   ARC = Academic Research Consortium   BMS = bare-metal stent(s)   CI = confidence interval   DES = drug-eluting stent(s)   MACE = major adverse cardiac events   MI = myocardial infarction   PCI = percutaneous coronary intervention   RCT = randomized clinical trial   ST = stent thrombosis   TLR = target lesion revascularization   TVR = target vessel revascularization

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J. Am. Coll. Cardiol. 2008 51: A35-A36. [Full Text] [PDF]