There are no medical therapies indicated for reduction of limb ischemic events. Studies of
dual-antiplatelet therapy with aspirin and clopidogrel versus aspirin alone (CASPAR) as well
as studies of systemic anticoagulation (WAVE) have shown no benefit for either strategy in
the reduction in limb vascular events. Surgical bypass grafting involves harvesting of the
vein, warm ischemia with disruption of vaso vasorum, ischemia-reperfusion, and finally
heightened hemodynamic stress in the new arterial environment. Vein grafts rapidly remodel in
response to the increase in blood flow and pressure in an attempt to normalize them into
physiological range. The investigators have previously identified 3 distinct temporal phases
of the remodeling process: During the first 30 days following implantation is a critical
period of luminal enlargement which appears to be an endothelium-independent process. The
second phase occurs between 1 and 3 months and represents a period of stiffening of the vein
graft indicating synthesis of fibrous proteins. The third period is referred to as
biochemical remodeling wherein the vein recovers clinically measureable endothelial function.
It is likely diabetes mellitus impacts each of these phases. TRA2°P-TIMI 50 demonstrated a
reduction in acute limb ischemic (ALI) events (42% reduction) and urgent peripheral arterial
revascularizations (35% reduction), a finding unique among medical therapies. While the
temporal trend in reduction in ALI events occurred early and late after exposure suggestion
an antithrombotic mechanism, the reduction in elective revascularization occurred later
suggested beneficial effects beyond platelet inhibition. The purpose of this trial is to
study the physiological impact of vorapaxar on lower extremity bypass graft maturation and
function.
Phase:
Phase 4
Details
Lead Sponsor:
Vanderbilt University Vanderbilt University Medical Center