Introduction A new generation of carotid artery stents that use a dual micromesh layer to reduce embolic events during carotid artery stenting has recently been introduced. We aimed to analyze the effectiveness and safety of the new Casper-RX stent in patients experiencing acute ischemic stroke with large vessel intracranial occlusion associated with a tandem lesion (another carotid occlusion or severe stenosis).
Methods We retrospectively analyzed all consecutive patients treated with carotid Casper-RX stents from our stroke registry. We analyzed clinical, angiographic, and neuroimaging data. Endpoints included acute intra-stent thrombus formation, stent occlusion prior to hospital discharge, 3 month modified Rankin Scale score (mRS), and symptomatic intracranial hemorrhage.
Results 21 patients were included: 10 patients had tandem carotid occlusions and 11 patients had severe carotid stenosis, 8 of whom had a hemodynamically significant stenosis. We observed acute in-stent thrombus formation in 11 patients. No stent occlusion occurred prior to hospital discharge. We report no stroke recurrence at 3 months but symptomatic intracranial hemorrhage in two patients. mRS score at 3 months was 0–2 (favorable) for 15 patients (71%), 3–5 for 3 patients, and 6 for 3 patients.
Conclusions In the present series, we frequently observed clot formation during the procedure with Casper-RX stents, which required periprocedural intravenous infusion of anticoagulant and antiplatelet treatment. This motivated us, in the absence of a prospective randomized controlled study demonstrating the non-inferiority of micromesh dual layer stents compared with the single layer design, to discontinue using this stent type in acute stroke requiring carotid angioplasty.
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Background and purpose
Stent assisted angioplasty of the extracranial internal carotid artery has a risk of periprocedural stroke due to dislodgement of debris from the carotid plaque. Recently, the Casper-RX stent (MicroVention, Tustin, California, USA), a double layered micromesh low profile closed cell stent with higher mesh density and smaller pore size compared with conventional stents, was developed to reduce the risk of distal embolism.1 2 However, in acute ischemic stroke, a retrospective case controlled study reported that the recently introduced dual layer stents have a higher risk of acute occlusion compared with single layer stents in acute stroke treatment.3 They argued that the higher metal density of these dual layer stents increases thrombogenicity in patients not previously prepared with dual antiplatelet therapy. Few post-market studies prove the effectiveness and safety of this newer stent in patients harboring symptomatic and asymptomatic carotid occlusive disease, and preloaded with dual antiplatelet therapy.1 4 5 We performed a retrospective analysis of patients who had acute ischemic stroke with large vessel intracranial occlusions associated with extracranial tandem lesions (another carotid occlusion or severe stenosis) treated with Casper-RX stents with an emphasis on acute stent thrombosis.
Materials and methods
In this retrospective study, we identified a consecutive series of patients from our prospective stroke database, Acute STroke Registry and Analysis of Lausanne (ASTRAL). We collected all patients experiencing acute ischemic stroke with large vessel intracranial occlusion and a tandem lesion (ie, another carotid occlusion or severe stenosis) treated with one or more carotid Casper-RX stents from November 2014 to August 2017. Eligibility criteria for procedures of mechanical thrombectomy were: (1) National Institutes of Health Stroke Scale (NIHSS) score of ≥4; (2) modified Ranking Scale (mRS) score of ≤2; (3) confirmed anterior circulation large vessel intracranial occlusion (M1, M2) associated with a tandem carotid lesion (severe stenosis or occlusion); (4) Alberta Stroke Program Early CT Score (ASPECTS) ≥5; and (5) initiation of mechanical thrombectomy within 8 hours of symptom onset. Our ethics committee waived patient consent for retrospective analysis using the ASTRAL registry.
The carotid Casper-RX stent is a nitinol double layer closed cell micromesh design. This construction is designed to prevent plaque prolapse. It comes in a 143 cm 5.2 F catheter with a 0.014 inch guidewire. The stent diameters are 5–10 mm and lengths 16–40 mm. A stent can be repositioned in the catheter with up to 50% extrusion for improved positioning, as determined by the operator. The Casper-RX device is currently not approved by the Food and Drug Administration for sale or use in the USA.
All procedures were performed with the patient under general anesthesia. We placed a balloon guide catheter or a long sheet into the common carotid artery after common femoral artery puncture. Balloon carotid angioplasty was done to get access to the intracranial occlusion; carotid assisted stenting (CAS) was performed after successful intracranial recanalization (modified Thrombolysis in Cerebral Infarction (mTICI) 2b/3). If balloon assisted angioplasty was insufficient for intracranial access, we performed CAS before mechanical intracranial thrombectomy. Balloon assisted angioplasty was done after stent placement to improve conformability. We did not use distal protection devices. Intravenous aspirin (250–500 mg) was administrated to all patients immediately after stent deployment. We started a 300 mg loading dose of clopidogrel on day 1 for patients treated with recombinant tissue plasminogen activator (rt-PA), and for the others, after the end of the procedure once the patient was awake. We continued the double antiplatelet therapy for 3 months after the procedure.
In all cases, clinical follow-up was assessed by NIHSS at 24 hours, at hospital discharge, and by mRS at 90 days. We analyzed stent patency with cervical CT angiography or cervical sonography.
We obtained the following data from ASTRAL using picture archiving and communication system (PACS) reports: patient demographics, cerebrovascular risk factors, pre-stroke mRS, prior antiplatelet or anticoagulant treatment, pre- and per-procedural medicaments, side and location of the intracranial occlusion, type of carotid involvement (severe stenosis or occlusion), number and size of carotid stents and balloon catheters, carotid vessel wall apposition of stents, acute in-stent thrombus formation defined as partial or total lack of opacification in the lumen of the stent, carotid residual stenosis, DSA mTICI, and symptomatic intracranial hemorrhage.
Categorical variables are expressed as absolute values (percentages), and quantitative variables as mean±SD or median (IQR), as appropriate.
Twenty-one patients were included in this study with a follow-up of 90 days. Mean age was 71.3±9.8 years (range 51–88); 38.1% were women. table 1. Nine patients (42.9%) had single or double antiplatelet treatment; none had anticoagulation treatment. All patients had a pre-stroke mRS score of 0–2. Patient baseline characteristics are summarized in table 1.
The median presenting NIHSS score was 15 (IQR 9.5–19). Eighteen (85.7%) patients received intravenous rt-PA. One patient was preloaded with aspirin and clopidogrel prior to intervention. All other patients without previous antiplatelet treatment received 250–500 mg of aspirin during the procedure. Intravenous heparin (range 50–70 UI/kg) was used in seven patients periprocedurally (three patients already treated with intravenous rt-PA). DSA confirmed acute carotid occlusion in 10 patients and severe carotid stenosis in 11 patients. Carotid disease and hemispheric clot location was predominantly on the left side (61.9%). Fifteen (71.4%) patients had intracranial occlusion on the M1 middle cerebral artery segment and six (28.6%) on the M2 middle cerebral artery segment. In 18 patients, one carotid Casper-RX stent was used, in 2 patients two stents were used, and three stents were used in 1 patient. Vessel wall apposition was complete in 20 patients and incomplete in 1 patient. We observed acute thrombus formation inside the stent after deployment in 11 (52.4%) cases; we treated this angiographic complication with repeated intra-stent balloon carotid angioplasty, and in 3 patients we added intravenous heparin to rt-PA and antiplatelet therapy. Modified TICI 2b-3 was obtained in 20 patients and mTICI 2a in 1 patient.
The mean time from symptom onset to arterial puncture was 230.1 (±94) min. The mean time from symptom onset to recanalization was 312.6 (±103) min. Emboli to an additional vascular territory (distal anterior cerebral artery (ACA)) was observed in three patients, in which two were observed before and one following deployment of the CASPER-RX stent. We found distal perforation and consequent subarachnoid hemorrhage in one patient. The study procedural characteristics are summarized in table 2.
The median NIHSS score at 24 hours, available for 19 patients, was 3 (IQR 1–7), and we report two symptomatic cerebral hemorrhagic complications. All carotid stents were patent on patient discharge. In one case, CT angiography found a large non-occlusive clot inside the stent; we treated the patient for 3 months with aspirin and acenocoumarol. No stroke recurrence was observed at the 3 month follow-up. The mRS score at 3 months was 0–2 in 16 (76.2%) patients, 3–5 in 2 (9.5%) patients, and 6 in 3 (14.3%) patients.
In the HERMES meta-analysis,6–11 acute ischemic stroke due to tandem occlusions was underestimated, with only 122 found out of 1278 patients; nevertheless, the risk ratio in favor of intervention was 1.81 (95% CI 0.96 to 3.40), similar to intracranial occlusions. A recent pooled analysis12 and a meta-analysis13 confirmed these results for tandem occlusions but some questions remain. For example, should the intracranial or the cervical occlusion be recanalized first ? Should balloon carotid angioplasty or CAS be used for cervical occlusions and severe stenosis? What type of stent should be used for CAS?
Concerning stent technology, as mentioned in the introduction, new carotid stents designed to improve carotid plaque coverage and reduce intracranial thromboembolic events have been recently developed. These include the Casper-RX (Microvention) and Roadsaver (Terumo, Tokyo, Japan) with nitinol double layer closed cell micromesh and the C guard (Penumbra), a laser cut nitinol stent covered with a micromesh polymer. Preliminary clinical results with the new stents confirmed their effectiveness and safety over single layer stents.5 14 15 However, the clinical studies included patients with carotid stenosis and not acute ischemic stroke due to tandem occlusions. Yilmaz et al 3 retrospectively compared single layer stents with the Casper-RX dual layer stent for emergency treatment of tandem lesions and reported a significantly higher rate of acute stent occlusions with Casper-RX stents compared with single layer stents. They suggested that the second micromesh layer increased thrombogenicy in cases of insufficient antiplatelet pretreatment. In our series of 21 consecutive patients with acute ischemic stroke due to tandem occlusions or stenosis treated with Casper-RX stents, we observed different results, in that all stents in survivors were patent at patient discharge. We do not have a clear explanation for this difference.
Our series is different from that of Yilmaz et al’s in two respects. First, most of our patients received rt-PA (85.7%). Additionally, a loading dose of clopidogrel was given to all 17 survivors not already under dual antiplatelet therapy, while in the dual layer stent group of the Yilmaz et al series, rt-PA was used in 30.0% of patients and a loading dose of clopidogrel was used in only 27.8% of patients. Yilmaz et al found a higher rate of stent occlusions using Casper-RX stents in patients who did not receive intravenous rt-PA (45.5% vs 11.1%); however, the difference was not significant. Their sample size was very small and we suggest that there were too few participants to demonstrate a difference, as they pointed out in the paper’s limitations. Concerning acute in-stent thrombus formation however, our results are comparable with those of Yilmaz et al (50% in the dual layer group). We found in-stent thrombus formation in more than half of the patients and treated this complication with repeated in-stent balloon carotid angioplasty; in three patients we added intravenous heparin to rt-PA and antiplatelet therapy, exposing these patients to a higher risk of spontaneous or iatrogenic bleeding.
To corroborate this finding, we analyzed the records of all patients with acute tandem occlusions or severe stenosis treated with single layer carotid stents from November 2014 to September 2018. The rate of in-stent thrombus formation in single layer stents was lower than that in dual layer Casper-RX stents (33.3% vs 52.4%). Moreover, in the five patients with single layer stents and acute in-stent thrombus formation, we did not add any additional antithrombotic drugs and we resolved the thrombus either by repeated intra-stent balloon carotid angioplasty or by conservative management in the case of small thrombus formation along the stent strut at the level of the carotid plaque.
Our study limitations are its retrospective design, the limited number of patients, the lack of a matched comparison group, and the fact that patients were not consecutive (some cases used single layer stents and others carotid balloon angioplasty).
In conclusion, in our series of tandem occlusion acute ischemic stroke patients, we did not report Casper-RX stent occlusion prior to patient discharge after endovascular treatment. However, in-stent thrombus formation during the procedure was frequent, and for three patients, previously treated with aspirin and rt-PA, additional heparin therapy was required followed by a fatal hemorrhagic complication in one patient. Due to the high rate of in-stent thrombus formation, we decided not to use dual layer stents in acute tandem occlusion therapy even though a prospective randomized controlled study has yet to demonstrate the non-inferiority of these stents compared with a single layer design.
Melanie Price Hirt provided editorial assistance in the final version of the manuscript and was funded by the authors.
Contributors BB contributed to the conception and design of the work, analysis and interpretation of the data, and drafting the paper. FP contributed to acquisition of the data and critical revision. PJM contributed to acquisition of the data and critical revision. SDH contributed to critical revision. LV contributed to analysis and interpretation of the data, and critical revision. PM contributed to the conception and design of the work, acquisition of the data, and critical revision. GS contributed to the conception and design of the work, and critical revision. All authors approved the final version to be published.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.
Competing interests PM: speaker and consulting fees from Medtronic, Steering committee of PROMISE (Penumbra). All this support goes to the institution and is used for stroke education and research. The other authors report no conflicts.
Ethics approval The Swiss ethics committee (Canton of Vaud) approved collection, analysis and publication of data from ASTRAL registry.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Additional unpublished data are available upon request.
Patient consent for publication Not required.