- Email: [email protected]
Randomized Comparison of Paclitaxel-Eluting Balloon Angioplasty Plus Stenting Versus Standard Balloon Angioplasty Plus Stenting Versus Directional Atherectomy for Symptomatic Femoral Artery Disease (ISAR-STATH)
Abstracts Michael C. Dalsing, MD, SECTION EDITOR
Randomized Comparison of Paclitaxel-Eluting Balloon Angioplasty Plus Stenting Versus Standard Balloon Angioplasty Plus Stenting Versus Directional Atherectomy for Symptomatic Femoral Artery Disease (ISAR-STATH) Ott I, Cassese S, Groha P, Steppich B, Hadamitzky M, Ibrahim T, et al. Circulation 2017;135:2218-26. Conclusions: Treatment of de novo superficial femoral artery (SFA) lesions with paclitaxel-eluting balloon (PEB) angioplasty, followed by stenting, is superior to balloon angioplasty (BA) and stenting or directional athererctomy (DA) regarding angiographic diameter stenosis at 6 months and target lesion restenosis (TLR) at 24 months. Summary: The many percutaneous avenues of treating the SFA include balloon angioplasty, stents, atherectomy, and various combinations. The ISAR-STATH (Intravascular Stenting and Angiographic Results: A randomized trial comparing paclitaxel-eluting balloon angioplasty plus stenting versus standard balloon angioplasty plus stenting versus directional atherectomy for symptomatic femoral artery disease) trial was a prospective, randomized, active-controlled, open-label trial at two German centers designed to assess the effects of stenting after PEB angioplasty compared with stenting after conventional BA or DA on SFA restenosis in patients with intermittent claudication. The angiographic inclusion was a de novo stenosis >70% to 100% occlusion of the SFA. Exclusion criteria were significant untreated inflow disease (>70% iliac artery stenosis), acute ischemia from SFA occlusion, previous SFA stenting, popliteal stenosis >70%, or renal insufficiency (estimated glomerular filtration rate <30 mL/min/1.73 m2) as well as life expectancy <1 year and contraindication to required medications. Randomization was by sealed envelopes containing computer-generated sequence after the decision to intervene was made and was to a 1:1:1 ratio. In general, the lesion was crossed with a 0.014-inch guidewire and supporting 4F catheter with a small “dissection reentry” 0.035-inch guidewire if intraluminal passage was not possible. With the wire in the distal lumen, randomization took place. In both angioplasty cohorts, predilation to a vessel-to-balloon ratio of 1:1 was achieved with a standard balloon. In the PEB angioplasty group, an additional dilation of the entire lesion with a PEB for 2 minutes was preformed to a 1:1 diameter just before nitinol stent placement oversized by 1 mm (Smart Stent) and exceeding the lesion length by 5 mm on each side. The BA cohort was treated with stent placement in a similar fashion, and in both groups, poststent balloon angioplasty used standard balloons. In the DA cohort, a Spider filter was deployed in the popliteal artery for distal protection, and the SilverHawk plaque excision system was used to remove plaque. If residual stenosis was >50% or flow-limiting dissection was present, inflation with standard BA to a 1:1 diameter for 1 minute at low pressure was attempted with a nitinol stent placed for persistent residual stenosis of >50% or flow-limiting dissection. Technical success was defined as <30% residual stenosis. Peri-interventional medications were 500 mg of aspirin (12 hours before by mouth or intravenously at the time of the intervention) and 5000 units of intra-arterial heparin. Postintervention medications were aspirin (100 mg daily) indefinitely and clopidogrel (75 mg) for at least 6 months. Follow-up was by phone or visit at 6 and 12 months. Repeat angiography was scheduled at 6 to 8 months. The study primary end point was diameter stenosis by angiographic measurement at 6 months. Secondary end points were binary restenosis frequency (>50% diameter stenosis) at 6 months, TLR at 24 months, time to onset and incidence of peripheral vascular events (amputation, revascularization, bypass surgery) at 24 months, and all-cause mortality at 24 months. All TLRs were clinically driven and angiographically confirmed before treatment. Sample sized determination was stated. Continuous data were expressed as mean 6 standard deviation, and categoric data were expressed as counts or proportions (%). The Student t-test, Wilcoxon rank sum test, or c2 test was used for group comparison. Event-free survival was assessed by Kaplan-Meier with log-rank testing. A two-sided P value of <.017 was considered statistically significant. From July 2009 to November 2013, 499 patients were treated with de novo femoropopliteal disease (Rutherford 2-6), with 155 patients meeting study criteria and randomized to PEB/stent (n ¼ 48), BA/stent (n ¼ 52), and DA (n ¼ 55). The only difference in patient
672
demographics between the groups was that more DA patients had coronary artery disease. Overall lesion length was short (65.9 mm) but similar across groups. Patients in the PEB/stent group had significantly higher minimal lumen diameter (0.2 vs DA 0.7) and diameter stenosis (95.1% vs DA 86.3%), and the DA cohort had fewer total occlusion than the BA/stent group (44% vs 67%). Re-entry was needed in 62% of those patients with total occlusion. In the DA cohort, 14 needed bailout stenting, one needed a covered graft for perforation, and one needed prolonged balloon inflation for rupture. One DA patient who required a stent needed thrombolysis aspiration. Number of stents needed for PEB and BA were similar (1.3 vs 1.4, P ¼ .43). At 6 months, the respective cohorts (PEB vs BA vs DA) obtained angiography (n ¼ 30, 42, and 44). Between eight and 10 patients in each group at 6 months refused angiography due to lack of symptoms. In those without a 6-month angiogram, supplemental data demonstrated no difference in patient pretreatment demographics. The primary end point of angiographic diameter stenosis after 6 months was significantly decreased in patients receiving PEB angioplasty, followed by stenting (34% 6 31%), compared with BA, followed by stenting (56% 6 29%; P ¼ .009), or DA (55A% 6 29%, P ¼ .007). Secondary outcomes of binary stenosis were significantly different between PEB and DA as well as BA (23% vs 54% and 52%) and late lumen loss between PEB and BA (1.2 mm vs 2.4 mm). TLR and clinical outcome were not statistically different when comparing groups at 6 months. At 24 months, angiography was performed in 115 patients with mean clinical followup similar in all groups at 23 to 26 months. TLR was significantly decreased after PEB vs BA or DA (17% vs 37% and 53%), while the rate of target vessel thrombosis was highest in the PEB cohort compared with the BA or DA cohorts (15% vs 10% and 6%) but did not reach statistical significance. No amputations or bypass surgery was required in any group. Three patients experienced stent thrombosis, with thrombus aspiration and stenting resolving the problem. Mortality was similar over time and between groups. One patient in the PEB group died of hemorrhagic shock caused by a retroperitoneal bleed the day after the intervention. Two in the PEB cohort and one in the BA group died of cardiac disease in late follow-up. Comments: There are some inconsistencies in this manuscript regarding the details of clinical follow-up, no mention of a planned angiogram at 24 months, although this did occur in most patients, the presence of few patients with rest pain/ulcers in a claudication study, and the lack of definitions, such as what TLR means. The lesion length was a mean of <7 cm, so is borderline even for the need for other than standard balloon angioplasty. Directional atherectomy with salvage stent placement does not perform as well as angioplasty and planned stent placement, bringing into question the need for atherectomy in these cases. My impression would be high cost for no benefit regarding atherectomy use. PEB with stenting does perform better over time but at a risk (1 early death and a 15% risk of target vessel thrombosis). The short lesion length and cost of treating simple claudication with several costly devices brings into question the study’s utility in the real world.
Low-dose Paclitaxel-coated Versus Uncoated Percutaneous Transluminal Balloon Angioplasty for Femoropopliteal Peripheral Artery Disease: 1-year Results of the ILLUMENATE European Randomized Clinical Trial Schroeder H, Werner M, Meyer DR, Reimer P, Kruger K, Jaff MR, et al. for the ILLUMENATE EU RCT Investigators. Circulation 2017;135:2227-36. Conclusions: Superiority with a low-dose paclitaxel-coated balloon (DCB) when used for femoropopliteal interventions was demonstrated over standard balloon percutaneous transluminal angioplasty (PTA) by both safety and effectiveness end points. Summary: This prospective, randomized, multicenter (18 European sites), single-blinded trial was designed to assess the safety and effectiveness of the next-generation low-dose (2 mg/mm2 surface dose of paclitaxel) DCB in the treatment of symptomatic patients with superficial femoral artery (SFA) or proximal popliteal artery (PA) occlusive
Randomized Comparison of Paclitaxel-Eluting Balloon Angioplasty Plus Stenting Versus Standard Balloon Angioplasty Plus Stenting Versus Directional Atherectomy for Symptomatic Femoral Artery Disease (ISAR-STATH) Ott I, Cassese S, Groha P, Steppich B, Hadamitzky M, Ibrahim T, et al. Circulation 2017;135:2218-26. Conclusions: Treatment of de novo superficial femoral artery (SFA) lesions with paclitaxel-eluting balloon (PEB) angioplasty, followed by stenting, is superior to balloon angioplasty (BA) and stenting or directional athererctomy (DA) regarding angiographic diameter stenosis at 6 months and target lesion restenosis (TLR) at 24 months. Summary: The many percutaneous avenues of treating the SFA include balloon angioplasty, stents, atherectomy, and various combinations. The ISAR-STATH (Intravascular Stenting and Angiographic Results: A randomized trial comparing paclitaxel-eluting balloon angioplasty plus stenting versus standard balloon angioplasty plus stenting versus directional atherectomy for symptomatic femoral artery disease) trial was a prospective, randomized, active-controlled, open-label trial at two German centers designed to assess the effects of stenting after PEB angioplasty compared with stenting after conventional BA or DA on SFA restenosis in patients with intermittent claudication. The angiographic inclusion was a de novo stenosis >70% to 100% occlusion of the SFA. Exclusion criteria were significant untreated inflow disease (>70% iliac artery stenosis), acute ischemia from SFA occlusion, previous SFA stenting, popliteal stenosis >70%, or renal insufficiency (estimated glomerular filtration rate <30 mL/min/1.73 m2) as well as life expectancy <1 year and contraindication to required medications. Randomization was by sealed envelopes containing computer-generated sequence after the decision to intervene was made and was to a 1:1:1 ratio. In general, the lesion was crossed with a 0.014-inch guidewire and supporting 4F catheter with a small “dissection reentry” 0.035-inch guidewire if intraluminal passage was not possible. With the wire in the distal lumen, randomization took place. In both angioplasty cohorts, predilation to a vessel-to-balloon ratio of 1:1 was achieved with a standard balloon. In the PEB angioplasty group, an additional dilation of the entire lesion with a PEB for 2 minutes was preformed to a 1:1 diameter just before nitinol stent placement oversized by 1 mm (Smart Stent) and exceeding the lesion length by 5 mm on each side. The BA cohort was treated with stent placement in a similar fashion, and in both groups, poststent balloon angioplasty used standard balloons. In the DA cohort, a Spider filter was deployed in the popliteal artery for distal protection, and the SilverHawk plaque excision system was used to remove plaque. If residual stenosis was >50% or flow-limiting dissection was present, inflation with standard BA to a 1:1 diameter for 1 minute at low pressure was attempted with a nitinol stent placed for persistent residual stenosis of >50% or flow-limiting dissection. Technical success was defined as <30% residual stenosis. Peri-interventional medications were 500 mg of aspirin (12 hours before by mouth or intravenously at the time of the intervention) and 5000 units of intra-arterial heparin. Postintervention medications were aspirin (100 mg daily) indefinitely and clopidogrel (75 mg) for at least 6 months. Follow-up was by phone or visit at 6 and 12 months. Repeat angiography was scheduled at 6 to 8 months. The study primary end point was diameter stenosis by angiographic measurement at 6 months. Secondary end points were binary restenosis frequency (>50% diameter stenosis) at 6 months, TLR at 24 months, time to onset and incidence of peripheral vascular events (amputation, revascularization, bypass surgery) at 24 months, and all-cause mortality at 24 months. All TLRs were clinically driven and angiographically confirmed before treatment. Sample sized determination was stated. Continuous data were expressed as mean 6 standard deviation, and categoric data were expressed as counts or proportions (%). The Student t-test, Wilcoxon rank sum test, or c2 test was used for group comparison. Event-free survival was assessed by Kaplan-Meier with log-rank testing. A two-sided P value of <.017 was considered statistically significant. From July 2009 to November 2013, 499 patients were treated with de novo femoropopliteal disease (Rutherford 2-6), with 155 patients meeting study criteria and randomized to PEB/stent (n ¼ 48), BA/stent (n ¼ 52), and DA (n ¼ 55). The only difference in patient
672
demographics between the groups was that more DA patients had coronary artery disease. Overall lesion length was short (65.9 mm) but similar across groups. Patients in the PEB/stent group had significantly higher minimal lumen diameter (0.2 vs DA 0.7) and diameter stenosis (95.1% vs DA 86.3%), and the DA cohort had fewer total occlusion than the BA/stent group (44% vs 67%). Re-entry was needed in 62% of those patients with total occlusion. In the DA cohort, 14 needed bailout stenting, one needed a covered graft for perforation, and one needed prolonged balloon inflation for rupture. One DA patient who required a stent needed thrombolysis aspiration. Number of stents needed for PEB and BA were similar (1.3 vs 1.4, P ¼ .43). At 6 months, the respective cohorts (PEB vs BA vs DA) obtained angiography (n ¼ 30, 42, and 44). Between eight and 10 patients in each group at 6 months refused angiography due to lack of symptoms. In those without a 6-month angiogram, supplemental data demonstrated no difference in patient pretreatment demographics. The primary end point of angiographic diameter stenosis after 6 months was significantly decreased in patients receiving PEB angioplasty, followed by stenting (34% 6 31%), compared with BA, followed by stenting (56% 6 29%; P ¼ .009), or DA (55A% 6 29%, P ¼ .007). Secondary outcomes of binary stenosis were significantly different between PEB and DA as well as BA (23% vs 54% and 52%) and late lumen loss between PEB and BA (1.2 mm vs 2.4 mm). TLR and clinical outcome were not statistically different when comparing groups at 6 months. At 24 months, angiography was performed in 115 patients with mean clinical followup similar in all groups at 23 to 26 months. TLR was significantly decreased after PEB vs BA or DA (17% vs 37% and 53%), while the rate of target vessel thrombosis was highest in the PEB cohort compared with the BA or DA cohorts (15% vs 10% and 6%) but did not reach statistical significance. No amputations or bypass surgery was required in any group. Three patients experienced stent thrombosis, with thrombus aspiration and stenting resolving the problem. Mortality was similar over time and between groups. One patient in the PEB group died of hemorrhagic shock caused by a retroperitoneal bleed the day after the intervention. Two in the PEB cohort and one in the BA group died of cardiac disease in late follow-up. Comments: There are some inconsistencies in this manuscript regarding the details of clinical follow-up, no mention of a planned angiogram at 24 months, although this did occur in most patients, the presence of few patients with rest pain/ulcers in a claudication study, and the lack of definitions, such as what TLR means. The lesion length was a mean of <7 cm, so is borderline even for the need for other than standard balloon angioplasty. Directional atherectomy with salvage stent placement does not perform as well as angioplasty and planned stent placement, bringing into question the need for atherectomy in these cases. My impression would be high cost for no benefit regarding atherectomy use. PEB with stenting does perform better over time but at a risk (1 early death and a 15% risk of target vessel thrombosis). The short lesion length and cost of treating simple claudication with several costly devices brings into question the study’s utility in the real world.
Low-dose Paclitaxel-coated Versus Uncoated Percutaneous Transluminal Balloon Angioplasty for Femoropopliteal Peripheral Artery Disease: 1-year Results of the ILLUMENATE European Randomized Clinical Trial Schroeder H, Werner M, Meyer DR, Reimer P, Kruger K, Jaff MR, et al. for the ILLUMENATE EU RCT Investigators. Circulation 2017;135:2227-36. Conclusions: Superiority with a low-dose paclitaxel-coated balloon (DCB) when used for femoropopliteal interventions was demonstrated over standard balloon percutaneous transluminal angioplasty (PTA) by both safety and effectiveness end points. Summary: This prospective, randomized, multicenter (18 European sites), single-blinded trial was designed to assess the safety and effectiveness of the next-generation low-dose (2 mg/mm2 surface dose of paclitaxel) DCB in the treatment of symptomatic patients with superficial femoral artery (SFA) or proximal popliteal artery (PA) occlusive