The Value of Screening for HPR in Patients Undergoing Lower Extremity Arterial Endovascular Interventions
The Value of Screening for HPR in Patients Undergoing Lower Extremity Arterial Endovascular Interventions
This is a randomized controlled trial designed to evaluate the role of screening for and
 intervening on patients with high on treatment platelet reactivity undergoing lower extremity
 arterial endovascular interventions.
Peripheral arterial disease (PAD) affects millions of people worldwide. Management of PAD has
 evolved from open surgery to an endovascular first approach leading to increased volume of
 endovascular interventions. Endovascular femoropopliteal intervention has emerged as a
 standard treatment for symptomatic PAD with acceptable patency rates.

 Histologic observation of bare metal stents with early failure shows association with
 platelet rich thrombus, high counts of platelets, and neutrophils associated with stent
 struts. Additionally, high inflation pressures associated with balloon angioplasty often
 causes local tissue damage leading to platelet activation. These findings led to studies
 targeting platelet activation following endovascular treatment showing improved outcomes in
 patients receiving stronger platelet inhibition.

 The current standard of care is prescription of dual antiplatelet therapy (DAPT) for
 femoropopliteal angioplasty or stenting. DAPT is active use of any two antiplatelet agents,
 often low dose aspirin plus P2Y12 inhibitor (clopidogrel, ticagrelor, prasugrel). There is
 improved stent patency and reduced adverse cardiovascular events in patients taking DAPT
 versus aspirin monotherapy.

 Clopidogrel is the most common additional antiplatelet agent prescribed, but 4-65% of
 patients taking clopidogrel fail to achieve clinically expected platelet inhibition. This
 persistent platelet reactivity despite compliant antiplatelet use is commonly referred to as
 high on-treatment platelet reactivity (HPR), and increases risk of endovascular intervention
 failure and associated adverse clinical events in these patients. Clopidogrel is a pro-drug
 metabolized by CYP2C19 enzyme into its active form. Failure to respond appropriately to
 clopidogrel is largely due to genetic polymorphisms within CYP2C19 enzyme resulting in
 variable metabolization of clopidogrel into the active metabolite.

 Alternative antiplatelet medications can overcome HPR through different metabolic pathways,
 but unfortunately at a significantly higher cost. Of these, ticagrelor is often used to
 overcome HPR for patients taking clopidogrel with favorable outcomes. However, regional cost
 for ticagrelor is $352.50 compared to $1.96 for clopidogrel. Cost and bleeding concerns among
 providers have prevented widespread use. Overall, there is paucity of evidence looking at HPR
 and lower extremity arterial endovascular interventions without consensus or guidelines on
 how to address this problem. Thus, the investigators propose an unblinded, randomized
 controlled trial in patients having femoropopliteal angioplasty or stenting comparing two
 strategies: 1. testing and treating for HPR versus 2. guideline based therapy without testing
 for HPR.
Inclusion Criteria:

 -  Peripheral arterial disease

 -  Planned angioplasty or stenting of superficial femoral artery or popliteal artery.

 Exclusion Criteria:

 -  Patients treated on an emergency basis

 -  Planned intervention on prior site of open surgical intervention (autogenous or
 autologous bypass, endarterectomy, or patch angioplasty)

 -  Planned intervention at site exclusive of superficial femoral artery or popliteal
 artery

 -  Planned re-stenting at site of prior stent placement

 -  Planned re-angioplasty at site of prior angioplasty

 -  Known inability to tolerate antiplatelet regimen before enrollment

 -  Patients who plan on receiving follow up care outside the University of Pittsburgh
 Medical Center

 -  Current use of prasugrel or ticlopidine

 -  Current use of oral anticoagulation medication

 -  Pregnant patients