During the study period, 75 patients underwent endovascular intervention for FP-ISR. 28 cases were Class I (focal ≤50 mm), 22 were Class II (diffuse, >50 mm), and 25 were Class III ISR (chronic total occlusion). Thirty-nine (52%) of the patients had stents initially implanted during endovascular limb salvage for critical limb ischemia; the indication for the initial intervention did not differ among groups. The median time from initial stent implantation to treatment for ISR was 9.5 months (IQR 6.9–13.3 months), without any difference among groups.
The baseline characteristics of the patients at the time of treatment for ISR were similar regardless of ISR class, with a high prevalence of diabetes, coronary artery disease, and current or former smoking (). Preprocedure statin use was also similar among groups, ranging from 79 to 84%. The indication for the ISR intervention was primarily claudication among patients with Class I or Class II ISR, whereas a majority of patients with Class III ISR (56%) underwent intervention for critical limb ischemia. No patients initially treated for claudication subsequently presented with critical limb ischemia due to FP-ISR, and all of the patients with critical limb ischemia and FP-ISR had their initial stent placed during treatment for critical limb ischemia.
Baseline Patient Characteristics
The angiographic characteristics for each ISR class are summarized in . The mean length of ISR for each class was 26, 135, and 178 mm, respectively. Patients with Class III ISR were more likely to have TASC II C/D lesions at the time of intervention for FP-ISR. Patients with Class III ISR also more frequently had restenotic lesions that extended into both the SFA and popliteal arteries (11, 27, and 48% for class I, II, and III respectively, P = 0.01). The overall stent fracture rate was 17%, with similar fracture rates among groups. However, all of the severe stent fractures (grade 3–4) occurred among patients with Type III ISR (P = 0.02). There was no difference in rates of below-knee runoff or reference vessel diameter among the three ISR classes.
Treatment characteristics are summarized in . There was significant heterogeneity in treatment approach related to the ISR class due operator preference for a given modality as a function of FP-ISR complexity. Patients with Class I ISR were more frequently (61%) treated with either balloon or cutting balloon angioplasty alone, whereas only one patient (4%) with Class III ISR was treated with cutting balloon angioplasty alone (P < 0.001). Laser atherectomy was the most common adjunctive debulking technique, representing 45 and 60% of the Class II and III ISR cases, respectively (P < 0.001 vs. Class I). Laser atherectomy was used both in conjunction with balloon angioplasty and with stenting. Placement of a new stent was most common (56%) among patients with Class III ISR. Covered stent grafts were used in 11, 23, and 16% of the patients with Class I, II and III FP-ISR.
Fig. 1 Study Design. Patients were categorized by type of in-stent restenosis and the treatment modality utilized. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Procedural success was achieved in 74/75 (99%) of patients. During the procedure, two cases of distal embolization occurred among patients undergoing laser atherectomy, and both patients were successfully treated with aspiration thrombectomy with restoration of distal flow. One case of flow-limiting dissection occurred in a patient with Class I ISR for whom balloon angioplasty alone was initially attempted; this patient was treated successfully with provisional stenting. Postprocedure, all groups had significant improvement in ABI and TBI measurements at 30 days (), with a mean ABI gain of 0.28 ± 0.2 (P < 0.001 compared with preprocedure ABI). All but one patient had stable or improved Rutherford classification at 30-day follow up. There were no subsequent major amputations of the ipsilateral limb among any of the study subjects. Six deaths occurred over a median follow up of 2 years: one in a patient with class I ISR, and five in patients with class III ISR (P = 0.1). All six of these patients had critical limb ischemia.
During long-term follow-up to 2 years, the Kaplan-Meier estimated rates of restenosis were 39% for Class I ISR, 67% for Class II ISR, and 72% for Class III ISR (P = 0.04). Compared to Class I ISR, Class III ISR was associated with a significantly higher risk of restenosis (HR 2.4, 95% CI 1.1–5.6) (). Reocclusion rates at 2 years were 8% for Class I ISR, 11% for Class II ISR, and 52% for Class III ISR (P = 0.009). Class III ISR was also independently associated with an increased risk of occlusion during long-term follow-up (HR 5.8, 95% CI 1.8–19) when compared to Class I or Class II ISR (). The 2-year rates of target vessel revascularization were similar among groups: 39% for Class I ISR, 28% for Class II ISR, and 32% for Class III ISR (P = 0.7). Although patients with Class III ISR had higher absolute rates of subsequent bypass surgery, the difference was not statistically significant (HR 3.4, 95% CI 0.6–20), ().
Fig. 2 Rates of Restenosis by ISR Classification. Overall restenosis rates were high. Type III (total occlusion of the stent) ISR was associated with higher rates of recurrent restenosis than type I or type II ISR. [Color figure can be viewed in the online issue, (more ...)
Fig. 3 Rates of Occlusion by ISR Classification. Type I (focal) and type II (diffuse) ISR were associated with low subsequent rates of subsequent stent occlusion, while type III (occlusion of the stent) was associated with significantly higher rates of reocclusion. (more ...)
Fig. 4 Rates of Bypass Surgery By ISR Classification. There was a nonsignificant trend toward higher rates of subsequent surgical bypass among patients with type III ISR. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com (more ...)