In-stent restenosis patients with severe claudication or critical limb ischaemia should be treated with drug-coated technologies if they present with focal lesions and with a mechanical block such as covered stents if they have diffuse lesions or occlusion, according to Koen Deloose, Dendermonde, Belgium.
Deloose, AZ Sint-Blasius Hospital, who spoke about when and how in-stent restenosis should be treated at the International Symposium on Endovascular Therapeutics (SITE; 24–27 June, Barcelona, Spain), said that even with modern generation nitinol stents a 20–25% rate of in-stent restenosis at one year is reported in the superficial femoral artery. “It is the Achilles’ heel of the superficial femoral artery treatment,” he noted.
He explained that patients can be divided into asymptomatic (Rutherford 0 or Fontaine I), claudicants (Rutherford 1–3 or Fontaine IIa–IIb) and critical limb ischaemia patients (Rutherford 4–6 or Fontaine III–IV), and that at his institution, asymptomatic patients and mild claudicants are treated with best medical therapy, lifestyle modifications and supervised exercise, while severe claudicants and critical limb ischaemia with in-stent restenosis or reocclusions receive an endovascular treatment. He added that the Tosaka classification of in-stent restenosis by visual estimate on angiography divides lesion into three classes: class I includes focal lesions (≤50mm in length), class II consists of diffuse lesions (>50mm in length) and class III are totally occluded lesions.
“Based on this we select a chemical block—drug-eluting balloon or drug-eluting stent—for Tosaka I and II lesions in order to inhibit smooth muscle cell migration and proliferation. For Tosaka III we select a mechanical block—a covered stent—to create a physical barrier and remove the stimulus for in-stent restenosis from the equation,” Deloose said.
At SITE, he reviewed the results of endovascular intervention for in-stent restenosis published in the literature, supporting the use of chemical blocks.
In a single-centre registry of 39 patients, he said, Stabile et al (JACC 2012; 60:1739–1742) used the IN.PACT Admiral drug-coated balloon (Medtronic). After one year the primary patency was 92.2% and after two years, 70.3%. Another trial using the IN.PACT Admiral device, the prospective, multicentre PLAISIR registry of 43 patients (38% Tosaka I, 60% Tosaka II and 2% Tosaka III class), showed a freedom from target lesion revascularisation of 90.5% at 12 months.
The DEBATE-ISR trial by Liistro et al (JACC 2012; 60:B97), a single-centre trial of 44 diabetic patients (mean lesion length 131mm) treated with IN.PACT Admiral and compared to an angioplasty historical cohort showed, after one year, positive results with drug-coated balloon in relation to primary patency (80.5%, p=0.046) and freedom from target lesion revascularisation (86.4% at 12 months, p<0.001, and 68% at 24 months). The benefit over angioplasty, however, was lost at two years.
In the FAIR trial (Krankenberg et al), a multicentre, randomised trial, 119 patients (62 drug-coated balloon vs. 57 plain angioplasty), with mean lesion length 82mm, at one year positive results for primary patency and freedom from target lesion revascularisation were in favour of the drug-coated balloon group. At one year recurrent restenosis was 29.5% with drug-coated balloon vs. 62.5% with plain angioplasty (p=0.004), and freedom from target lesion revascularisation was 90.8% with drug-coated balloon vs. 52.6% with plain angioplasty (p=0.0001).
The COPA CABANA trial, a prospective, randomised trial by Tepe et al compared the use of the Cotavance drug-coated balloon (Bayer) vs. plain angioplasty for symptomatic superficial femoral artery in-stent restenosis lesions in 88 patients (Rutherford 2–5). The mean lesion length was 119.8mm in the drug-coated balloon arm and 109.3mm in the plain angioplasty arm. “Again we see superior freedom from target lesion revascularisation with the drug-coated balloon (90% vs. 40%) at eight months and less late lumen loss at six months (0.3 vs 1.6) at the six-month follow-up,” Deloose said.
With regard to drug-eluting stents, Deloose discussed the data from the single-arm study of Zilver PTX (Cook Medical) including 119 patients with in-stent restenosis and mean lesion length of 133mm. The primary patency rate at one year was 78.8% and freedom from target lesion revascularisation after one year was 81% and at two years, 60.8%.
In terms of covered stents for in-stent restenosis, he stated that data were scarce with only single-centre, non-randomised data. “In this context we set up the RELINE trial, a physician-initiated, randomised, controlled multicentre trial comparing the new generation Viabahn endoprosthesis (Gore) and plain angioplasty in the treatment of femoral in-stent restenosis,” he said.
RELINE recruited 83 patients with Rutherford class 2–5, 39 treated with the covered stent and 44 with plain angioplasty. The mean lesion lengths were 173mm for Viabahn and 190mm for plain angioplasty. After one year the primary patency in the Viabahn group was 74.8% and in the plain angioplasty group it was 28% (p<0.001). After two years, it decreased to 58.4% in the Viabahn group and 11.6% in the plain angioplasty group (p<0.001). Freedom from target lesion revascularisation was 80% with Viabahn and 42% with plain angioplasty at one year (p<0.001) and 66.3% vs. 23% (p<0.001) at two years.
In conclusion, Deloose said, severe claudicants and critical limb ischaemia patients have to be treated for in-stent restenosis. He added, “There is more and more evidence that chemical solutions (drug-coated balloons and stents) are valuable, at least in the short and medium term, in the battle against in-stent restenosis. The RELINE results prove, even in the longer run, that a mechanical barrier (such as the Viabahn endoprosthesis) is also a promising tool for the treatment of in-stent restenosis.”