of preferred terms that were used for case identification. Primary MACE defined by us
and custom MACE defined by the Agency had the shortest list of preferred terms
consisting of 54 and 33 terms, respectively. We identified 41 patients with primary
MACE and 40 patients with custom MACE. In contrast, SMQ MACE defined by the
FDA was based upon a list of 148 preferred terms. As expected, this more broadly
defined endpoint identified a larger number of patients; that is, 141 patients. The
relationship of these four endpoints is important for the interpretation of the results.
based on searching for 117 preferred terms in the MedDRA dictionary. We identified 61
patients with acute CV events. Subsequent to submitting the NDA, we analyzed MACE
(Major Adverse Cardiovascular Events). MACE was a composite endpoint that
encompassed CV death, nonfatal myocardial infarction, and nonfatal stroke. Three
definitions of MACE were initially investigated. For each type of MACE, case
identification was based upon searching the adverse event database using specific lists of
preferred terms supplemented by clinical review of all deaths to ensure that each death
with a CV etiology was counted.
endpoints using a series of Venn diagrams. The relationship with the two most broadly
defined endpoints, SMQ MACE and acute CV events, is described at the top of the slide.
There were 141 patients with SMQ MACE and 61 patients with acute CV events. There
were 46 patients in the overlap; that is, patients whose events were classified as both
As can be seen in this slide, the three types of MACE varied in the breadth
On the next slide I'll explain the relationship of patients with these
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relatively broad endpoint that included both reversible and irreversible ischemic
events. It also included revascularization procedures.
Cases of acute CV events were identified in the adverse event database