broad SMQ MACE endpoint is a composite endpoint that included all cardiovascular
deaths and all preferred terms in the SMQ for myocardial infarction and central nervous
system hemorrhages and cerebrovascular accidents. On the other hand, the so-called
custom MACE is essentially a subset of the broad SMQ MACE. It was developed by
collaboration and consensus of three FDA reviewers.
populations and the intent of choosing these endpoints was twofold. First, to broadly
capture all possible strokes and myocardial infarctions and secondly to more specifically
include terms which when chosen by the investigator were likely to represent true
myocardial infarction or stroke. It is with this intent that the agency termed these
endpoints, broad SMQ MACE and custom. These endpoints separately with the addition
of cardiovascular deaths were thus chosen as the MACE endpoints of interest.
to represent events that would truly be an MI or stroke and that represented events, which
were acute and atherosclerotic in mechanism. The complete list of all terms used on both
endpoints is included in your briefing document. Here, I provide examples of which
terms were chosen for these two endpoints. Under myocardial infarction terms, acute MI
was chosen for both the broad and custom endpoints while blood CPK increased was
listed only under broad. Under stroke terms, CVA was listed under both endpoints, while
paralysis was chosen for broad only.
I will now more specifically define each of these endpoints. The so called
In defining these endpoints, we selected terms, which seemed highly likely
the incidence of custom MACE data for all treatment groups, for both the short-term and
short-term plus long-term periods. These numbers represent the first event for a subject.
Scribes, LLC Toll Free 1-800-675-8846 www.scribesllc.com
FDA requested two separate endpoints be analyzed for these
I will now start presenting results of the analyses. In this slide, I present