Results from the GAIA-DEB study published online ahead of print in the Journal of Endovascular Therapy show no sustained benefit of dilation with a drug-coated balloon before the placement of the Igaki-Tamai bioresorbable scaffold in the superficial femoral artery. In the study, the use of the paclitaxel-coated balloon had no impact on the prevention of restenosis after 12 months.
GAIA-DEB was a single-centre, prospective, non-randomised study conducted by Martin Werner, Vascular Clinic, Hanusch Hospital, Vienna, Austria, and colleagues from the Department for Interventional Angiology, University Hospital Leipzig, Germany. It was designed to evaluate the efficacy and safety of the biodegradable Igaki-Tamai scaffold (Kyoto Medical Planning) after treatment of de novo atherosclerotic superficial femoral artery lesions with a paclitaxel-coated balloon (IN.PACT Admiral, Medtronic).
“Mechanical stabilisation of the lesion after balloon dilation is still required in a substantial proportion of patients to eliminate early causes of reobstruction, including dissections, residual stenoses, and acute vessel recoil. Optimally this would be achieved without leaving a permanent stimulus for neointima proliferation in the vessel. Against this background the implantation of a biodegradable scaffold may offer the advantage of avoiding long-term mechanical irritation that induces restenosis,” the authors write. They note that the first experiences with the Igaki-Tamai biodegradable scaffold in the superficial femoral artery have been published; however, restenosis was observed in 68% of patients after one year. They add, “It has been hypothesised that the scaffold resorption process induced an inflammatory response thereby causing intimal proliferation and restenosis. Based on this assumption, pretreatment with an antiproliferative drug might inhibit this process, leading to improved patency rates.”
Between 31 January and 3 August 2011, 20 claudicant patients (mean age 66.7±11.6 years; 14 men) with atherosclerotic superficial femoral artery disease were enrolled in the study. The mean lesion length was 43.6±16.3mm, the mean diameter stenosis was 89.7±8.4% and mean ankle brachial index at rest before intervention was 0.71±0.16. The target lesions were mainly situated in the mid and distal superficial femoral artery. The investigation excluded patients with severe calcification. Patients were evaluated through 12 months following the implant procedure.
The Igaki-Tamai scaffold is made of a poly-L-lactic acid (PLLA). Within the first six months, the scaffold retains its radial strength and flexibility to potentially prevent restenosis, thereafter it is absorbed. A long-term follow-up report (Nishio et al. Circulation 2012;125:2343–2353) suggested that the Igaki-Tamai scaffold required three years to disappear totally from human coronary arteries.
Nineteen patients completed the follow-up schedule. One patient died of heart failure 109 days after the procedure; the Clinical Events Committee adjudicated this death as unrelated to the procedure or the device. Through the 12-month follow-up, of 33 serious adverse events recorded, 25 were not related to the device or procedure and the other eight were clinically-driven target lesion revascularisations.
At one-month follow-up, duplex ultrasound showed no restenosis; but there were two cases among the 19 patients completing six-month follow-up. The restenosis rates for the nine- and 12-month points were 42% and 58%, respectively. Primary and secondary patency rates at one year were 42% and 100%, respectively. Average ankle brachial index increased from 0.71±0.16 at baseline to 1.15±0.17 following treatment. The means at the six-, nine-, and 12-month follow-up visits were 1.03±0.21, 0.95±0.26, and 0.99±0.30, respectively (all p<0.05 vs. baseline). At 12 months, the ankle brachial index was improved ≥0.15 compared to baseline in 12 patients.
At six-month follow-up, 18 of 19 patients had an improved walking capacity compared to baseline, and 14 patients had improved their walking speed. Ten patients could climb stairs with less trouble. At 12 months, 16 patients showed improvements in walking distance compared with baseline; 12 patients improved their walking speed and nine could climb stairs with less trouble.
The authors discuss that in a previous study (GAIA), the Igaki-Tamai biodegradable scaffold was shown to be safe for the treatment of femoropopliteal atherosclerotic lesions and improved the acute result of balloon dilation by effectively treating residual stenosis and dissections. However, in that study, a high incidence of recurrent obstruction of the treated arterial segment was observed during the first six months of follow-up. Histopathological analysis revealed intimal hyperplasia as the main cause of in-stent restenosis.
“Since use of a balloon coated with an antiproliferative drug has been shown to reduce intimal hyperplasia, the current study investigated if pretreatment of the vessel with paclitaxel before implantation of a bioabsorbable scaffold had the potential to reduce restenosis induced by the process of scaffold degradation,” they write, and add, “Indeed, the six-month restenosis rate was very favourable at only 10% compared to 39% at that time point in the GAIA study. However, during the second half of the year, the catch-up phenomenon led to a high incidence of reobstruction resulting in a 12-month restenosis rate of 58%, which did not differ significantly from the 68% restenosis rate in the GAIA study. The angiographic pattern of restenosis did not differ from restenosis in conventional nitinol stents, with diffuse restenosis throughout the entire stent length.”
The authors conclude that the high rates of restenosis and reintervention seen in the study currently do not support the use of this combination. They say that possible solutions to improve the results of bioabsorbable scaffolds in the superficial femoral artery are different drug coating formulas that prolong the antiproliferative effects in the vessel wall, as well as drug-eluting bioabsorbable scaffolds with pharmacokinetics matched to the scaffold’s absorption process.
The investigators note that the main limitations of this study are related to the small number of patients and lack of direct comparison to standard treatment. A future trial is planned to investigate the drug-coated Remedy stent, an improved version of the Igaki-Tamai scaffold with increased stent strength and an antiproliferative coating, also from Kyoto Medical Planning.