Five-Year Freedom From Target-Lesion Revascularization Using Excimer Laser Ablation Therapy in the Treatment of In-Stent Restenosis of Femoropopliteal Arteries

Abstract: Background. Target-lesion revascularization (TLR) and loss of patency remain high following treatment of in-stent restenosis (ISR) of the femoropopliteal (FP) artery. Excimer laser atherectomy (ELA) is effective in reducing TLR and improves patency at 6-month and 1-year follow-up when compared with balloon angioplasty (PTA). The long-term sustainability of these early results is unknown. We present a retrospective analysis from our center on the 5-year outcomes of ELA in the treatment of ISR of the FP arteries. Methods. Patients who underwent ELA for FP-ISR from February 2005 to April 2010 at a single medical center were included. Demographics, angiographic and procedural variables were included. Major adverse events and 5-year TLR and target-vessel revascularization were obtained from medical records. Descriptive analysis was performed on all variables. Kaplan-Meier survival curves for TLR were plotted censored for death among patients who died before the occurrence of a TLR. Results. Forty consecutive patients (mean age, 67.2 ± 9.0 years; 57.5% males) were included. Angiographic variables included: lesion length, 210.4 ± 104.0 mm; lesion severity, 93.9 ± 8.9%; and number of vessel runoffs, 1.7 ± 1.0. All patients were treated with adjunctive PTA. Acute procedural success was achieved in 92.5% of vessels. Distal embolization requiring treatment was 2.5%. No unplanned amputation occurred. Total deaths occurred in 8/40 (20%). At 5-year follow-up, TLR occurred in 62.5% with the steepest decline in freedom from TLR occurred in the first year followed by a less decline in the subsequent 2 to 3 years. Conclusion. ELA for FP-ISR continues to show progressive increase in TLR up to 5-year follow-up, but mostly occurs in the first 3 years after index procedure. These data suggest that a minimum follow-up of 3 years is needed to determine stability of treatment of FP-ISR with laser. 

J INVASIVE CARDIOL 2017;29(6):207-208.

Key words: atherectomy, in-stent restenosis, femoropopliteal segment, excimer laser, long-term outcome

A recent meta-analysis of prospective trials has shown that balloon angioplasty (PTA) of femoropopliteal in-stent restenosis (FP-ISR) has a target-lesion revascularization (TLR) rate of approximately 27% at 6 months and 42.6% at 1 year.¹ The restenosis and TLR rates are particularly high for long lesions and total occlusions.² Several alternative methods have been proposed to treat FP-ISR. In prospective trials, covered stents,³ laser ablation,⁴ and drug-coated balloons^5,6 have shown superiority over PTA in reducing TLR and improving patency in these lesions. Excimer laser has shown to be superior to PTA in treating FP-ISR at 1 year, but a significant drop in patency and freedom from TLR were seen after the first 6 months post treatment.⁴ The loss of patency and high TLR rate are seen for all ablative therapies used to treat FP-ISR^7-11 and one retrospective study at 1 year suggested continued loss of patency beyond 1 year.¹² The sustainability of initial treatment of FP-ISR with laser debulking remains unclear on long-term follow-up.¹³

In this study, we evaluate freedom from TLR in a consecutive cohort of patients treated with excimer laser (Spectranetics) for FP-ISR from a single tertiary medical center. 

Methods

The 1-year acute and follow-up data on this patient cohort have been previously published.⁸ Briefly, 40 consecutive patients treated with Laser Elite excimer laser were included. Adjunctive PTA was performed in 100% of cases. 

We present 5-year follow-up on patients by reviewing medical records by a dedicated research coordinator. The study was approved by the institutional review board. The primary effectiveness endpoint was clinically driven TLR at 5-year follow-up. 

Descriptive analysis was done on all variables. Continuous variables were presented as mean ± standard deviation and dichotomous variables as percentages. Kaplan-Meier survival curve for TLR was plotted censored for death. 

Results

A total of 40 patients were included. The majority of patients had claudication (73.7%) and a high prevalence of diabetes (47.5%). The mean lesion length was 210.4 ± 104.0 mm and 47.5% of lesions were TASC D. Stenting was performed in 50% of patients. Acute procedural success (<30% angiographic residual narrowing) occurred in 92.5% of patients with the following adverse events reported: distal embolization requiring treatment, 2.5% (1 patient with no embolic filter protection); planned minor amputation, 2.6%; planned major amputation, 2.6%; total death, 7.7% (all cardiac related). One perforation occurred, and was treated successfully with stenting and balloon inflation. The Laser Elite was the predominantly used device. 

At 1 year, TLR occurred in 48.7% of patients. At 5-year follow-up, no unplanned amputation occurred. Total deaths occurred in 8/40 patients (20%). TLR occurred in 62.5%, with the steepest decline in freedom from TLR occurring in the first year followed by less decline in the subsequent 2 to 3 years. Figure 1 displays the Kaplan-Meier plot for freedom from TLR over the course of the 5-year follow-up period. 

Discussion

Debulking strategies have been attempted to reduce restenotic tissue burden in FP-ISR.^4,7-12 Laser debulking has shown to be superior to PTA in these lesions at 1-year follow-up,⁴ but long-term data are lacking and the durability of this treatment beyond 1 year is uncertain. In this study, we demonstrate that loss of freedom from TLR continues to occur up to 3 years and does plateau afterward, indicating that an adequate follow-up period in testing this strategy needs to be extended to at least 3 years. Our data in the first 2 years are consistent with a previously published 2-year report on the laser in FP-ISR.¹² The findings in our study are mostly based on the use of the Laser Elite. It is unclear whether a more aggressive debulking strategy with the Turbo Tandem or Turbo Power lasers could change the course of TLR over the course of a 5-year period. 

The overall TLR rate remains high, indicating that without a biological modifier such as paclitaxel, patients will likely be frequently retreated for recurrence of restenosis. Laser atherectomy alone or with adjunctive PTA remains overall suboptimal for treating FP-ISR despite its apparent superiority to PTA alone. Long-term data on the combination of excimer laser and drug-coated balloons will be necessary to evaluate this strategy. 

References

1.    Shammas NW, Jones-Miller S, Lemke J. Meta-analysis-derived benchmarks of patency and target lesion revascularization of percutaneous balloon angioplasty from prospective clinical trials of symptomatic femoropopliteal in-stent restenosis. J Vasc Interv Radiol. 2016;27:1195-1203. 

2.    Tosaka A, Soga Y, Iida O, et al. Classification and clinical impact of restenosis after femoropopliteal stenting. J Am Coll Cardiol. 2012;59:16-23. 

3.    Bosiers M, Deloose K, Callaert J, et al. Superiority of stent-grafts for in-stent restenosis in the superficial femoral artery: twelve-month results from a multicenter randomized trial. J Endovasc Ther. 2015;22:1-10.

4.    Dippel EJ, Makam P, Kovach R, et al. Randomized controlled study of excimer laser atherectomy for treatment of femoropopliteal in-stent restenosis: initial results from the EXCITE ISR trial (EXCImer Laser Randomized Controlled Study for Treatment of FemoropopliTEal In-Stent Restenosis). JACC Cardiovasc Interv. 2015;8:92-101.

5.    Krankenberg H, Tübler T, Ingwersen M, et al. Drug-coated balloon versus standard balloon for superficial femoral artery in-stent restenosis: the Randomized Femoral Artery In-Stent Restenosis (FAIR) trial. Circulation. 2015;132:2230-2236. 

6.    Kinstner CM, Lammer J, Willfort-Ehringer A, et al. Paclitaxel-eluting balloon versus standard balloon angioplasty in in-stent restenosis of the superficial femoral and proximal popliteal artery: 1-year results of the PACUBA trial. JACC Cardiovasc Interv. 2016;9:1386-1392. 

7.    Schmidt A, Zeller T, Sievert H, et al. Photoablation using the turbo-booster and excimer laser for in-stent restenosis treatment: twelve-month results from the PATENT study. J Endovasc Ther. 2014;21:52-60. 

8.    Shammas NW, Shammas GA, Hafez A, et al. Safety and one-year revascularization outcome of excimer laser ablation therapy in treating in-stent restenosis of femoropopliteal arteries: a retrospective review from a single center. Cardiovasc Revasc Med. 2012;13:341-344. 

9.    Shammas NW, Shammas GA, Helou TJ, et al. Safety and 1-year revascularization outcome of SilverHawk atherectomy in treating in-stent restenosis of femoropopliteal arteries: a retrospective review from a single center. Cardiovasc Revasc Med. 2012;13:341-344.

10.    Beschorner U, Krankenberg H, Scheinert D, et al. Rotational and aspiration atherectomy for infrainguinal in-stent restenosis. Vasa. 2013;42:127-133.

11.    Shammas NW, Shammas GA, Banerjee S, Popma J, Mohammad A, Jerin M. JetStream rotational and aspiration atherectomy in treating in-stent restenosis of femoropopliteal arteries: results of the JETSTREAM-ISR feasibility study. J Endovasc Ther. 2016;23:339-346.

12.    Armstrong EJ, Thiruvoipati T, Tanganyika K, et al. Laser atherectomy for treatment of femoropopliteal in-stent restenosis. J Endovasc Ther. 2015;22:506-513. 

13.    Shammas NW. Commentary: excimer laser in treating femoropopliteal in-stent restenosis: can early success be maintained over long-term follow-up? J Endovasc Ther. 2015;22:514-517. 

From the Midwest Cardiovascular Research Foundation, Davenport, Iowa.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr N. Shammas reports research and educational grants from Boston Scientific (full COI at www.mcrfmd.com). The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted December 18, 2016, provisional acceptance given December 28, 2016, final version accepted February 3, 2016.

Address for correspondence: Nicolas W. Shammas, MD, MS, FACC, FSCAI, President and Research Director, Midwest Cardiovascular Research Foundation, 1622 East Lombard Street, Davenport, IA 52803. Email: shammas@mchsi.com