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).
