Robustness of Longitudinal Safety and Efficacy After Paclitaxel-Based Endovascular Therapy for Treatment of Femoro-Popliteal Artery Occlusive Disease: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The aims of this study were: i) to assess fragility indices (FIs) of individual randomized controlled trials (RCTs) that compared paclitaxel-based drug-coated balloons (DCBs) or drug-eluting stents (DESs) versus standard endovascular devices, and ii) to meta-analyze mid-term and long-term safety and efficacy outcomes from available RCT data while also estimating the FI of pooled results. METHODS: This systematic review has been registered in the PROSPERO public database (CRD42022304326 http://www.crd.york.ac.uk/PROSPERO). A query of PubMed (Medline), EMBASE (Excerpta Medical Database), Scopus, and CENTRAL (Cochrane Central Register of Controlled Trials) databases was performed to identify eligible RCTs. Rates of primary patency (PP) and target lesion revascularization (TLR) were assessed as efficacy outcomes, while lower limb amputation (LLA) consisting of major amputation that is. below or above the knee and all-cause mortality were estimated as safety outcomes. All outcomes were pooled with a random effects model to account for any clinical and study design heterogeneity. The analyses were performed by dividing the RCTs according to their maximal follow-up length (mid-term was defined as results up to 2-3 years, while long-term was defined as results up to 4-5 years). For each individual outcome, the FI and reverse fragility index (RFI) were calculated according to whether the outcome results were statistically significant or not, respectively. The fragility quotient (FQ) and reverse fragility quotient (RFQ), which are the FI or RFI divided by the sample size, were also calculated. RESULTS: A total of 2,337 patients were included in the systematic review and meta-analysis. There were 2 RCTs examining DES devices and 14 RCTs evaluating different DCBs. For efficacy outcomes, there was evidence that paclitaxel-based endovascular therapy increased the PP rate and reduced the TLR rate at mid-term, with a calculated pooled risk ratio (RR) of 1.66 for patency (95% CI, 1.55-1.86; P < 0.001), with a corresponding number needed-to-treat (NNT) of 3 patients (95% CI, 2.9-3.8) and RR of 0.44 for TLR (95% CI, 0.35-0.54; P = 0.027), respectively. Similarly, there was evidence that paclitaxel-based endovascular therapy both increased PP and decreased TLR rates at long-term, with calculated pooled RR values of 1.73 (95% CI, 1.12-2.61; P = 0.004) and 0.53 (95% CI, 0.45-0.62; P = 0.82), respectively. For safety outcomes, there was evidence that paclitaxel-based endovascular therapy increased all-cause mortality at mid-term, with a calculated pooled RR of 2.05 (95% CI, 1.21-3.24). However, there was no difference between treatment arms in LLA at mid-term (95% CI, 0.1-2.7; P = 0.68). Similarly, neither all-cause mortality nor LLA at long-term differed between treatment arms, with a calculated pooled RR of 0.66, 1.02 (95% CI, 0.31-3.42) and 1.02 (95% CI, 0.30-5.21; P = 0.22), respectively. The pooled estimates of PP at mid-term were robust (FI = 28 and FQ = 1.9%) as were pooled rates of TLR (FI = 18 and FQ = 0.9%). However, when safety outcomes were analyzed, the robustness of the meta-analysis decreased significantly. In fact, the relationship between the use of paclitaxel-coated devices and all-cause mortality at mid-term showed very low robustness (FI = 4 and FQ = 0.2%). At 5 years, only the benefit of paclitaxel-based devices to reduce TLR remained robust, with an FI of 32 and an FQ of 3.1%. CONCLUSIONS: The data supporting clinical efficacy endpoints of RCTs that examined paclitaxel-based devices in the treatment of femoral-popliteal arterial occlusive disease were robust; however, the pooled safety endpoints were highly fragile and prone to bias due to loss of patient follow-up in the original studies. These findings should be considered in the ongoing debate concerning the safety of paclitaxel-based devices.

Management of patch infections after carotid endarterectomy and utility of femoral vein interposition bypass graft.

OBJECTIVE: Patch infection after carotid endarterectomy (CEA) is a rare but devastating complication. A variety of different treatment options are reported; however, there is currently no consensus on how to manage this highly morbid problem. The purpose of this study was to review our experience with management of infectious patch complications after CEA and to highlight utility of femoral vein interposition bypass grafting. METHODS: All CEA patch infection operations at the University of Florida from 2002 to 2017 were reviewed retrospectively. Preoperative history, intraoperative details, and postoperative complications were recorded. Bypass patency was verified with duplex ultrasound imaging (1 month, 6 months, annually). The primary end point was 30-day stroke or death; secondary end points included cranial nerve injury, reintervention, reinfection, and survival. Life tables were used to estimate end points. RESULTS: Twenty-nine patients (mean age, 70 ± 9 years; male, 76%) were identified. The index CEA occurred at a median of 15 months (interquartile range, 1-55 months) preoperatively (39% <2 months after the index procedure). A variety of patch materials were implicated (Dacron, n = 9; unknown/undocumented, n = 8; bovine pericardium, n = 5; expanded polytetrafluoroethylene, n = 3; unidentified nonbiologic prosthetic, n = 3; saphenous vein, n = 1). Carotid reintervention antecedent to the infected patch presentation occurred in 41% (incision and drainage, n = 10; carotid stent, n = 2; vein patch, n = 1). The most common infecting organisms were Staphylococcus and Streptococcus species (52%; n = 15). The most frequent presentation (46%; n = 13) was pericarotid abscess or phlegmon (pulsatile neck mass or pseudoaneurysm, 28% [n = 8]; carotid-cutaneous fistula, 28% [n = 8]). Reconstruction strategy included femoral vein interposition bypass in 24 patients (83%; nonreversed configuration, 16/24 [67%]), saphenous vein patch in 4 patients (14%), and femoral vein patch in 1 patient (3%). Median postoperative length of stay was 5 days (interquartile range, 4-8 days). Twelve patients (41%) experienced a complication, and the 30-day stroke/death rate was 7% (death, n = 1; stroke, n = 1). The single postoperative death occurred in a patient with history of congestive heart failure who developed a pulseless electrical activity arrest on postoperative day 11 that resulted in multiorgan system failure. Cranial nerve injury occurred in 28% (n = 8; cranial nerves X [3], VII [2], XII [2], and IX [1]), all of which resolved by last follow-up. In follow-up (mean clinical follow-up, 17 ± 14 months; mean survival time, 108 months [95% confidence interval, 81-135 months]), two (7%) complained of limb edema with femoral cutaneous nerve palsy that resolved by 3 months. One interposition bypass occluded at 3 months (asymptomatic); the remaining grafts remained patent with no restenosis, reinfection, or reintervention events. The 1- and 5-year survival was 87% ± 6% and 82% ± 8%, respectively. CONCLUSIONS: CEA patch infection can be successfully managed with femoral vein interposition bypass with acceptable postoperative outcomes. Excellent patency can be anticipated with good long-term survival. This strategy can be considered especially in cases with carotid size mismatch or if there is limited availability of alternative biologic conduits.

Identification of optimal device combinations for the chimney endovascular aneurysm repair technique within the PERICLES registry.

OBJECTIVE: The ideal stent combination for chimney endovascular aneurysm repair remains undetermined. Therefore, we sought to identify optimal aortic and chimney stent combinations that are associated with the best outcomes by analyzing the worldwide collected experience in the PERformance of chImney technique for the treatment of Complex aortic pathoLogiES (PERICLES) registry. METHODS: The PERICLES registry was reviewed for patients with pararenal aortic disease electively treated from 2008 to 2014. Eleven different aortic devices were identified with three distinct subgroups: group A (n = 224), nitinol/polyester; group B (n = 105), stainless steel/polyester; and group C (n = 69), nitinol/expanded polytetrafluoroethylene. The various chimney stent subtypes included the balloon-expandable covered stent (BECS), self-expanding covered stent, and bare-metal stent. Deidentified aortic and chimney device combinations were compared for risk of chimney occlusion, type IA endoleak, and survival. Effects of high-volume centers (>100 cases), use of an internal lining chimney stent, number of chimney stents, and number of chimney stent subtypes deployed were also considered. We considered demographics, comorbidities, and aortic anatomic features as potential confounders in all models. RESULTS: The 1- and 3-year freedom from BECS chimney occlusion was not different between groups (group A, 96% ± 2% and 87% ± 5%; groups B and C, 93% ± 3% and 76% ± 10%; Cox model, P = .33). Similarly, when non-BECS chimney stents were used, no difference in occlusion risk was noted for the three aortic device groupings; however, group C patients receiving BECS did have a trend toward higher occlusion risk relative to group C patients not receiving a BECS chimney stent (hazard ratio [HR], 4.0; 95% confidence interval [CI], 0.85-18.84; P = .08). Patients receiving multiple chimney stents, irrespective of stent subtype, had a 1.8-fold increased risk of occlusion for each additional stent (HR, 1.8; 95% CI, 1.2-2.9; P = .01). Use of a bare-metal endolining stent doubled the occlusion hazard (HR, 2.1; 95% CI, 1.0-4.5; P = .05). Risk of type IA endoleak (intraoperatively and postoperatively) did not significantly differ for the aortic devices with BECS use; however, group C patients had higher risk relative to groups A/B without BECS (C vs B: odds ratio [OR], 3.2 [95% CI, 1-11; P = .05]; C vs A/B: OR, 2.4 [95% CI, 0.9-6.4; P = .08]). Patients treated at high-volume centers had significantly lower odds for development of type IA endoleak (OR, 0.2; 95% CI, 0.1-0.7; P = .01) irrespective of aortic or chimney device combination. Mortality risk was significantly higher in group C + BECS vs group A + BECS (HR, 5.3; 95% CI, 1.6-17.5; P = .006). The 1- and 3-year survival for groups A, B, and C (+BECS) was as follows: group A, 97% ± 1% and 92% ± 3%; group B, 93% ± 3% and 83% ± 7%; and group C, 84% ± 7% and 63% ± 14%. Use of more than one chimney subtype was associated with increased mortality (HR, 3.2; 95% CI, 1.4-7.5; P = .006). CONCLUSIONS: Within the PERICLES registry, use of nitinol/polyester stent graft devices with BECS during chimney endovascular aneurysm repair is associated with improved survival compared with other aortic endografts. However, this advantage was not observed for non-BECS repairs. Repairs incorporating multiple chimney subtypes were also associated with increased mortality risk. Importantly, increasing chimney stent number and bare-metal endolining stents increase chimney occlusion risk, whereas patients treated at low-volume centers have higher risk of type IA endoleak.