Stent and Non-Stent Based Outcomes of Infrainguinal Peripheral Artery Interventions From the Multicenter XLPAD Registry

Abstract: Background. There are limited data regarding contemporary use of stent and non-stent based treatment strategies of infrainguinal peripheral artery disease (PAD). Methods. We analyzed data from the ongoing multicenter XLPAD registry between July 2005 and October 2013 to report on the use of non-stent (atherectomy ± balloon angioplasty) and stent-based treatment of superficial femoral artery (SFA), popliteal, and below-the-knee (BTK) vessels in contemporary clinical practice. Results. A total of 584 interventions (SFA, 82.5%; popliteal, 7.2%; BTK, 9.9%) were performed in 372 patients (mean age, 63.2 years; diabetes mellitus, 57.7%; Rutherford category 1-3, 73.5%; Rutherford category 4-6, 20.1%). Stents were deployed in 389 lesions (66.6%; SFA, 90.5%; popliteal, 5.1%; BTK, 4.1%) and non-stent strategy (atherectomy, 49%) in 195 lesions (33.4%; SFA, 66.7%; popliteal, 11.3%; BTK, 21.5%). In the stent and non-stent groups, mean lesion lengths were 133.9 mm and 86.0 mm (P<.001), chronic total occlusions (CTOs) constituted 63.0% and 49.7% (P<.01), and restenotic lesions were 12.6% and 32.3% (P<.001), respectively. At a mean follow-up of 260 ± 130 days, in the stent and non-stent treated patients, all-cause mortality was 4.3% and 3.5% (P=.65), clinically indicated repeat revascularization was 17.5% and 14.9% (P=.42), and amputation was 4.6% and 9.2% (P<.01), respectively. SFA lesion location, long lesion length, and CTO were associated with the use of stents. Advanced Rutherford class was associated with a non-stent treatment strategy. Conclusion. The majority of endovascular peripheral arterial interventions are performed in the SFA; most include a CTO and occur in patients with diabetes mellitus. Operators use stents to primarily treat complex SFA lesions with overall similar outcomes, except for fewer amputations compared to a non-stent strategy.
 
J INVASIVE CARDIOL 2015;27(1):14-18
Key words: peripheral vascular disease, stenting, plain old balloon angioplasty, outcomes, superficial femoral artery

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Patients with peripheral artery disease (PAD) usually present with claudication or critical limb ischemia (CLI).¹ Of the lower-extremity infrainguinal arteries, which include the superficial femoral artery (SFA), popliteal artery, and below-the-knee (BTK) vessels (ie, the anterior tibial, posterior tibial, and peroneal arteries), PAD most frequently involves the SFA in claudicants, and has a more multilevel involvement in CLI.² The SFA courses through a fibromuscular canal, and as a result is subject to dynamic forces during ambulation, and is an unfavorable location for stent placement. Given their location, smaller caliber, and lack of approved stents for this location, BTK arteries are frequently treated with non-stent strategies.³ The purpose of this study is to report on the contemporary use of stent-based and non-stent based revascularization strategies for infrainguinal PAD, and its clinical outcomes from an ongoing multicenter PAD registry.

Methods

We analyzed data entered into the ongoing multicenter Excellence in PAD (XLPAD) registry (NCT01904851) between July 2005 and October 2013 to report use of atherectomy and/or balloon angioplasty (“non-stent” group) and stenting (“stent” group) for SFA, popliteal, and BTK vessel revascularization. We studied clinical and procedural records, baseline patient characteristics, lesion characteristics, procedural information, outcomes, and follow-up data entered into REDCap (Research Electronic Data Capture) online data capture software.⁴

Patients. Patient risk factors, comorbid disease conditions, laboratory data, and medications were derived from the patient electronic medical records and diagnosis codes. Tobacco users were defined as patients who currently used tobacco or had in the year prior to enrollment. All procedural information was obtained from abstraction of procedural notes and review of angiograms. Angiographic data regarding lesion length and lesion characteristics were obtained from the analysis of diagnostic and procedural angiograms performed at ten study locations. All angiograms were analyzed at a centralized angiography and ultrasound core laboratory.

Endpoints. Lesion length was defined by arterial segment with angiographic stenosis greater than 70%, while CTO length was defined as the distance between the proximal and distal caps on angiography. A single CTO was defined based on the presence of a single occlusion or sequential occlusions separated by ≤2 cm in the SFA and by ≤1 cm in BTK arteries. Placement of any number of stents assigned the patient to the stent group, while the non-stent group comprised patients who underwent balloon angioplasty with or without atherectomy.

We primarily compared symptom-driven target vessel revascularization (TVR) through 12 months after the index procedure. Second, we compared cardiovascular and limb-specific outcomes, a composite of all-cause death, non-fatal myocardial infarction (MI), ischemic stroke, periprocedural complications, and unplanned endovascular or surgical revascularization and amputation (both above and below the ankle) of the target limb through 12 months. We also compared changes in Rutherford category and/or ankle-brachial index (ABI) at 12 months compared to baseline. Target vessel or stent thrombosis were adjudicated based on angiographic appearance and procedure findings that included acuity of presentation, crossing strategy, aspiration of thrombotic material, and/or presence of embolic debris.

Statistical analysis. Continuous variables were reported as mean ± standard deviation, and discrete variables were reported as numbers and percentage values. Continuous variables were compared with a one-way ANOVA or the Wilcoxon rank-sum test, while discrete variables were compared with the Pearson chi-square test or the Fisher’s exact test, as appropriate. Logistic regression analysis was performed with stent use as the dependent variable. Predictors of stent use included lesion location, presence of CTO, Rutherford class, and lesion length.⁵ Statistical analyses were conducted using IBM SPSS version 20 (IBM SPSS) and SAS version 9.³ (SAS Institute).

Results

A total of 584 procedures were performed in 372 unique patients. The baseline characteristics are listed in Table 1. Overall, 88% of patients were male and average age was 63.2 ± 8.9 years. Most procedures were performed in patients presenting with claudication and with resting ABI <0.9. Diabetes mellitus (DM) was highly prevalent in the study cohort (57.7%), as was tobacco use (61.6%) and coronary artery disease (CAD; 75.3%). Aspirin was prescribed to 95.5% of patients, clopidogrel to 87%, and a lipid-lowering agent to 83.2%.

Procedural characteristics of stent and non-stent procedures are shown in Table 2; 79% of  lesions were de novo and 59% were CTOs. Average lesion length was 117.8 ± 79.2 mm and was significantly longer in the stent group compared with the non-stent group (133.9 ± 80.3 mm vs 86.0 ± 66.7 mm; P<.001). In the stent group, 91% of treated lesions were in the SFA, compared with 67% in the non-stent group (P<.001). A significantly greater number of non-stent procedures were performed in the BTK location compared with stenting (22% vs 4%; P<.001). CTOs comprised 63% of lesions in the stent group compared with 50% in the non-stent group (P<.01).

SFA lesion location was an important predictor of stent use (odds ratio [OR], 3.22; 95% confidence interval [CI], 1.80-5.75; P<.001) (Figure 1), as was the presence of CTO (OR, 1.58; 95% CI, 1.01-2.54; P=.05). The likelihood of stent use increased by 7% for every 1 cm increase in lesion length (OR, 1.07; 95% CI, 1.03-1.11; P<.001). However, an increase in 1 Rutherford class was associated with a 1.5-fold lower likelihood of receiving a stent (OR, 0.65; 95% CI, 0.46-0.91; P=.01).

Follow-up information was available in 86% of patients. At an average follow-up of 260 ± 130 days, mean ABI improved from 0.73 ± 0.31 to 0.83 ± 0.25 (P<.001) (Figure 2A). Claudication symptoms decreased from an average of 3.2 to 2.47 on the Rutherford scale, and significant improvement in symptoms was observed in both groups (Figure 2B).

Adverse events on follow-up are shown in Figure 3. Overall, 6.2% required amputation in the target limb (4.6% in the stent group and 9.2% in the non-stent group; P<.03) and 1.9% suffered an MI (2.6% in the stent group vs 0.51% in the non-stent group; P=.11). Target peripheral artery thrombosis was 3.4% (4.1% in the stent group vs 2.1% in the non-stent group; P=.20), and 16.6% required repeat endovascular intervention of the target limb, with no significant difference between the two groups (17.5% in the stent group vs 14.9% in the non-stent group; P=.42). A total of 7% of limbs required surgical revascularization (5.9% in the stent group vs 9.2% in the non-stent group; P=.14). Over 4% of patients died, with no differences between the groups. Clinical outcomes based on lesion location are shown in Figure 4. Need for amputation was 4.4% in patients who underwent an index femoropopliteal intervention, compared with 22.4% of those with BTK revascularization (P<.001). Again, 5.7% and 19% required surgical revascularization in the femoropopliteal and BTK groups, respectively (P<.001). There was no significant difference in the need for repeat target limb revascularization based on location of the index procedure (P=.14). Stent or target vessel thrombosis in the femoropopliteal location was 3.8% and 0% in BTK location, respectively (P=.63).

Discussion

These data from the XLPAD registry provide important insights into the contemporary use of stent and non-stent based revascularization procedures for the treatment of symptomatic infrainguinal PAD. Infrainguinal PAD in the SFA, longer lesion length, and presence of CTO are important predictors of stent use. Moreover, significantly more non-stent procedures are performed in the popliteal and BTK arterial locations, and have greater need for amputation and surgical revascularization compared with the stent group.

Operators use stents to primarily treat complex lesions with overall comparable outcomes to a non-stent strategy. Although non-stent treatments exhibit higher rates of surgical revascularization and amputation, this may be driven by a greater proportion of non-stent interventions performed in popliteal and BTK arterial locations, predominantly in patients with advanced Rutherford class. Patients with CLI are known to have greater severity of multilevel PAD and are more likely to experience adverse events, including amputation of the target limb, and higher all-cause mortality.^2,6,7 In our study, we did not observe higher all-cause mortality in the non-stent group; however, the amputation rate was significantly higher. We also observed a higher amputation rate in this study compared with those previously reported.^6,7 This could be attributed to: (1) pooling of above and below-the-ankle amputations; and (2) failure to capture planned vs unplanned amputations in the XLPAD registry. The high use of antiplatelet and lipid-lowering therapies in both study groups, along with inclusion of centers with well-developed PAD interventional programs in the XLPAD registry, may have contributed to the lower than expected mortality of patients in both groups.^7,8

Stent-based procedures were longer and required greater fluoroscopy times. These procedures tackled a larger number of CTOs and longer lesion lengths. Importantly, the need for repeat revascularization in the study was 30% at an average follow-up of 8.7 months. This high rate of repeat revascularization is consistent with results observed in a randomized trial of infrainguinal interventions in diabetics with >50% CTO and average lesion lengths >100 mm, and points to the need for applying alternative therapeutic strategies and technologies to improve outcomes in patients undergoing infrainguinal peripheral artery interventions.5 Although many trials have demonstrated superior patency of stents compared with balloon angioplasty for femoropopliteal PAD, they have been limited by relatively short lesion lengths, as well as under-representation of CTOs and patients presenting with CLI.^9-14 Currently, there are no randomized trials comparing stent-based and atherectomy-based therapies for femoropopliteal and BTK-PAD.

Another important observation from this study is that it reported on the incidence of stent or target vessel thrombosis. This was observed exclusively in the stent group despite high use of antiplatelet therapy with aspirin and clopidogrel. However, the duration of dual-antiplatelet therapy was not captured as part of our study, and was left at the discretion of the operators. Future studies to test the impact of antiplatelet therapy duration on the durability of infrainguinal peripheral artery interventions are needed. The only randomized data in this area come from the results of the MIRROR (Management of Peripheral Arterial Interventions With Mono or Dual-Antiplatelet Therapy) study, which reported lower target lesion revascularization in only 20 patients treated with clopidogrel and aspirin compared with aspirin alone for a period of 6 months.¹⁵

Study limitations. This study is limited by missing follow-up information, selection bias due to non-randomized treatment assignments, predominantly male cohort, lack of data on minor or major amputations, the planned or unplanned nature of amputations, and duration of antiplatelet therapy. In addition, there is a lack of device-specific information, stent types, and procedural data such as crossing times, radiation dose area product, and absence of patients with drug-coated peripheral stents. These limitations are being addressed as part of the ongoing XLPAD registry data capture.

Despite these limitations, the findings of this study provide important insights regarding contemporary use of stent and non-stent based treatments for endovascular treatment of infrainguinal PAD in the United States.

Conclusion

Operators use stents to primarily treat complex infrainguinal PAD, with overall similar outcomes compared with non-stent based interventions, except for lower need for target-limb amputations.

References

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From 1University of Texas Southwestern Medical Center, Dallas, Texas; 2Veteran Affairs North Texas Healthcare System, Dallas, Texas; 3University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma; 4Seton Heart Institute, Austin, Texas; 5El Paso Cardiac and Endovascular Center, El Paso, Texas; 6Cardiothoracic and Vascular Surgeons, Austin, Texas; 7Arkansas Heart Hospital, Little Rock, Arkansas; 8St. Louis Veteran Affairs Medical Center, St. Louis, Missouri; 9Midwest Cardiovascular Research Foundation, Davenport, Iowa; and 10University of Texas Health Science Center San Antonio, San Antonio, Texas.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Banerjee reports grants from Boston Scientific and The Medicines Company; personal fees from Gilead, St. Jude, Cordis Corporation, Boehringer Ingerheim, Sanofi, and Medtronic; ownership of MdcareGlobal (spouse); and intellectual property from HygeiaTel. Dr Abu-Fadel reports personal fees from Abbott Vascular. Dr Addo reports personal fees from AstraZeneca, St. Jude, and Abbott Vascular. Dr Brilakis reports grants and personal fees from Sanofi, Janssen, St Jude Medical, Terumo, Asahi, Abbott Vascular, and Boston Scientific; grant from Guerbet; spouse employed by Medtronic. Dr Foteh reports grants from Terumo, Angioscore, Cardiovascular Systems, Abbott Vascular, and Cook Medical. Dr Gigliotti reports grants from Abbott Vascular, Medtronic, and AstraZeneca; personal fees from Janssen. Dr Luna reports personal fees from AstraZeneca and St. Jude. Dr Prasad reports personal fees from AstraZeneca, Gore, Abbott Vascular, and St. Jude Medical. Dr Shammas reports grants from Boston Scientific, Possis, Edwards, The Medicines Company, ev3, Schering-Plough, Fox-Hollow, Spectranetics, Atrium, Gilead, Medtronic, Genesis Foundation, CSI, Bayer, Abbott Vascular, AGA Medical, Astellas Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Cordis Vascular, Daiichi Sankyo, IDEV Technologies, Lilly USA, Pfizer, BMS, St. Jude Medical, Takeda Pharmaceuticals, Terumo Medical, and Zoll Lifevest; promotional programs for Boehringer Ingelheim, Forest Pharmaceuticals, Lilly/Daichii, Astra Zeneca, Pfizer/BMS, and Gilead. The remaining authors report no conflicts of interest.

Manuscript submitted May 29, 2014, and accepted June 23, 2014.

Address for correspondence: Subhash Banerjee, MD, 4500 S. Lancaster Rd. (111A), Dallas, TX 75216. Email: subhash.banerjee@va.gov