Excellence in Peripheral Arterial Disease Treatment of Superficial Femoral Artery Disease With Drug-eluting Stents

Current practice of SFA revascularization almost always results in use of a Nitinol (a
nickel-titanium alloy) BMS. Balloon angioplasty of complex SFA lesions, such as CTO or ≥60 mm
lesions is associated with >50% restenosis at 1-year and Nitinol stents have outperformed
stainless-steel stents in the SFA. Debulking strategies are employed selectively and rarely
as a stand-alone therapy of SFA CTO. Stent use in long SFA lesions and CTO is fraught with
the risk of fracture, mechanical deformation, neo-intimal hyperplasia and thrombosis, each of
which is associated with loss of patency. Repeat procedures for in-stent restenosis are
technically difficult, carry a higher morbidity compared to the initial procedure and provide
less symptom relief. Therefore improving the patency of the initial procedure is in the best
interest of the patient and the operator. Though long SFA lesions and CTO constitute ≥50% of
all SFA lesions, it is systematically under-represented in the current SFA randomized trials.
Stenting has not been shown to be superior to balloon angioplasty for short (30-60 mm) SFA
lesions.SFA stenting is associated with lower patency rates and is especially less durable in
diabetics, who have a higher prevalence of long lesions and CTO. In one of the largest to
date outcome analyses of Nitinol stents in the SFA, 56% of lesions constituted a CTO. Seventy
two percent of lesions treated with stents presented with in-stent restenosis compared to 52%
of lesions stented for non-CTO lesions (p<0.001). In a multivariate analysis of stent
patency, presence of a long lesion or CTO was an independent adverse predictor (hazard rate
or HR=5.075, 95% confidence interval or CI 2.715-9.487). It is important to note that the
benefit of stents is greater for longer and more complex lesions, including SFA CTO and long
(≥60 mm) lesions.

Study subjects will be recruited from the group of patients who are referred for clinically
indicated endovascular treatment of SFA for claudication at the Dallas VA Medical Center and
at other participating study sites. The study the investigators propose is significant
because: (a) it would affect many veterans, (b) the consequences of early SFA stent failure
are grave, (c) treatment of SFA lesions is challenging, and (d) outcomes after treatment of
SFA lesions are poor and may be improved with DES. In summary, failure of stent patency after
initial revascularization with stenting is common and carries significant morbidity. If
restenosis rates of SFA stents can be reduced with DES, it could significantly improve
procedural success, durability of treatment, quality of life of patients, reduce the need for
repeat revascularization procedures, and potentially reduce healthcare costs.

The proposed study is a phase 3, randomized controlled, parallel-group study in patients with
long SFA lesions and SFA CTO, undergoing clinically indicated stent-based percutaneous
revascularization.

End points :

The primary study end point is binary restenosis, as assessed by duplex ultrasonography
performed at 12 months post-procedure or earlier if clinically indicated. Binary restenosis
is defined as ≥2.5 fold increase in PSVR within the stented segment and within 10 mm of its
proximal and distal edges to that recorded proximal to the stented segment or by the presence
of an occluded stent with no flow. Secondary endpoints included change of resting
ankle-brachial index (ABI) and symptoms (Rutherford-Becker stages), at 12 months
post-procedure. Patients will be asked to complete a walking impairment questionnaire (score
range: 0 to 14,080) pre-intervention, and then at 12 months for the first year
post-procedure.19 All analyses will be performed in a blinded fashion at the Veterans Affairs
North Texas Clinical Angiographic and Ultrasound Core Laboratory and clinical adjudication
and adverse events monitoring will be performed by an independent data oversight and safety
monitoring board.

Statistical analysis :

The investigators calculated a priori that 55 vascular segments would be needed in each study
arm to have 80% power to detect a reduction in binary restenosis from 40% in the BMS arm to
15% in the DES arm, assuming 10% attrition and an alpha of 0.05. Continuous variables will be
summarized as mean ± standard deviation and compared using the t-test or the Wilcoxon
rank-sum test, as appropriate. Discrete variables will be presented as frequencies and group
percentages compared using the chi-square test or Fisher's Exact Test, as appropriate.
Freedom from restenosis will be assessed using Kaplan-Meier curves and log-rank test. For all
comparisons a two-sided probability of <0.05 will be considered statistically significant.
All analyses will be performed using SAS 9.1 (SAS Institute Inc., Cary, North Carolina).

Inclusion Criteria:

1. Age 18 years or older

2. Referred for clinically indicated lower extremity angiography and peripheral arterial
intervention

3. Willing and able to give informed consent. The patients must be able to comply with
study procedures and follow-up.

4. Absence of allergy to both clopidogrel and aspirin

5. Negative pregnancy test or breast-feeding

6. No coexisting conditions that limit life expectancy to less than 12 months or that
could affect a patient's compliance with the protocol as per the site investigator

7. Serum creatinine <2.5 mg/dL

8. Baseline hemoglobin >9 g/dl

9. Baseline platelet count >80,000/L

10. Absence of prior stroke or transient ischemic attack within 3 months

11. ≥30 days from any prior surgical or endovascular procedure

Angiographic enrollment criteria:

1. Undergoing SFA revascularization with the intention for stent implantation

2. De novo SFA lesion ≥60 mm in length by visual estimation

3. Successfully crossed de novo SFA CTO of any length by visual estimation

Exclusion Criteria:

1. SFA lesion involving <5mm of ostial SFA and/or profunda femoris artery take-off

2. SFA lesion extending below the medial femoral epicondyle

3. <1 vessel below-the knee (BTK) run-off