Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.

Safety and efficacy of tirofiban in acute ischemic stroke due to tandem lesions undergoing mechanical thrombectomy: A multicenter randomized clinical trial (ATILA) protocol.

Background: In-stent thrombosis after mechanical thrombectomy (MT) worsen outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Although an optimal antiplatelet therapy is needed, the best approach to avoid in-stent thrombosis is yet to be elucidated. Hypothesis: Low-dose intravenous tirofiban is superior to intravenous aspirin in avoiding in-stent thrombosis in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. Methods: The ATILA-trial is a multicenter, prospective, phase IV, randomized, controlled (aspirin group as control), assessor-blinded clinical trial. Patients fulfilling inclusion criteria (AIS due to TL, ASPECTS ⩾ 6, pre-stroke modified Rankin Scale ⩽2 and onset <24 h) will be randomized (1:1) at MT onset to experimental (intravenous tirofiban) or control group (intravenous aspirin). Intravenous aspirin will be administered at a 500 mg single dose and tirofiban at a 500 µg bolus followed by a 200 µg/h infusion during first 22 h. All patients will be followed up to 3 months. Sample size estimated is 240 patients. Outcomes: The primary efficacy outcome is the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. The primary safety outcome is the rate of symptomatic intracranial hemorrhage. Secondary outcomes include functional independence defined as modified Rankin Scale 0-2, proportion of patients undergoing rescue therapy due to in-stent aggregation during MT and carotid reocclusion at 30 days. Discussion: ATILA-trial will be the first clinical trial regarding the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. Trial registration: NCT0522596.

Comparing data from thrombectomy in m2 occlusion and proximal middle cerebral artery.

INTRODUCTION: Mechanical thrombectomy for large vessel occlusion in the anterior circulation has been shown to be beneficial. The question of whether this technique is safe and effective in the distal vasculature remains unanswered. We wanted to compare outcome data from mechanical thrombectomy of M2 branches of the middle cerebral artery (MCA) with those of the M1 segment, and better understand the clinical predictors of these M2 occlusions. METHODS: A retrospective analysis was performed of data prospectively collected between January 2017 and July 2021 from patients with acute ischemic stroke undergoing mechanical thrombectomy of isolated M1 or M2 branches of the MCA. RESULTS: 350 patients were identified, 287 with M1 and 63 with M2 occlusions. Mean age was 70.71 ± 12.55 and 75.21 ± 10.21 years, respectively (p = 0.0083). Baseline Alberta Stroke Program Computed Tomography (ASPECT) score was worse in the M1 cohort (7.68 ± 1.73 vs. 8.32 ± 1.54; p = 0.0079), while there was no significant difference in National Institutes of Health Stroke Scale (NIHSS) scores. No statistical disparity existed in mean procedure duration for each cohort; fewer thrombectomy attempts were required in the M2 cohort (2.01 vs. 1.63; p = 0.0478). There was no statistical difference in total time to recanalization (559.19 vs. 629.97, p = 0.2506). Similar rates of successful reperfusion were observed (Thrombolysis in Ischaemic Stroke score [TICI] ≥ 2b 80.84% vs. 71.43% p = 0.1221). Good outcome (modified Rankin scale ≤ 2) was 56.10 in M1 occlusions and 63.49% on M2 groups. Intracranial haemorrhage rates were similar. CONCLUSIONS: M2 thrombectomy is safe and a significant proportion of patients achieve a good clinical outcome. Advanced age, atrial fibrillation and previous treatment with anticoagulants were predictors for poor outcome. Good outcome was achieved when effective recanalization was obtained.

Intra- or peri-procedural rupture in the endovascular treatment of intracranial aneurysms.

INTRODUCTION: Intra- or peri-procedural aneurysm rupture is one of the most feared adverse effects associated with embolization. Our aim was to report the characteristics of patients suffering intra- or peri-procedural ruptures during embolization of cerebral aneurysms. PATIENTS AND METHODS: Between March 1994 and October 2021, 648 consecutive cerebral aneurysms were treated by endovascular procedure at our facility. Medical records were reviewed retrospectively with emphasis on procedure description, potential risk factors, and clinical outcomes related to intra- or peri-procedural rupture. RESULTS: Of the 648 patients, 17 (2.6%) suffered an intra- or peri-procedural hemorrhagic event. The most common location was the anterior communicating artery. There was no significant difference between previously ruptured and unruptured aneurysms in the incidence of bleeding. In four patients, bleeding was evident within 24 h after the procedure. The clinical evolution at three months was poor and only four patients presented a positive evolution. There were 11 deaths (64.71%). Balloon remodeling was associated with an increased frequency of ruptures, while stenting was a safer treatment. CONCLUSION: Aneurysmal rupture during endovascular therapy is unpredictable, and its occurrence can be devastating. The incidence is quite low although the outcome is frequently poor. Early detection and proper management, including prompt occlusion of the aneurysm, are important to achieve a positive outcome. Anterior communicating artery aneurysms and those treated with balloon catheters have a higher incidence of rupture. A small number of ruptures of uncertain origin occur that go unnoticed in digital subtraction angiograms.

Endovascular stroke treatment after 6-24 hours only needs non-contrast CT.

OBJECTIVES: Imaging selected patients with proximal anterior circulation stroke who demonstrate limited infarct may benefit from endovascular treatment beyond conventional time limits. Our aim was to evaluate the results of the EVT group series arriving between 6 and 24 hours from the onset of symptoms with (ASPECTS) ≥7 to our hospital (with 24/7 interventional neuroradiology) comparing them with those obtained in our prospectively registered series arriving between 0 and 6 hours. MATERIALS AND METHODS: The inclusion criteria were ≥18 years, an interval between stroke and endovascular treatment of 6-24 hours, prestroke score mRS 0-2, no intracranial haemorrhage, (NIHSS) scale 8-22 and infarct evaluated by CT scan ≥7 in ASPECTS scale. Data, including patient demographics, neuroimaging findings, procedural details, recanalization rates and 90-day mRS, were collected. RESULTS: Twelve of the 14 (85.71%) endovascular group patients who came to our centre between 6 and 24 hours had good outcomes at 90 days. To confirm our findings, we evaluated patients treated at our centre who met the selection criteria from January 2017 to September 2019. In this period, 382 patients with large vessel occlusion were treated endovascularly. 56 patients met all the criteria for inclusion and exclusion for our study. 31 of these 56 patients (56.36%) obtained a (mRS) scale ≤2 at three months. There was no significant difference (P = 0.063). CONCLUSION: In circumstances of difficult access to MRI or CT perfusion, a computed tomography of ASPECTS ≥7 is sufficient to indicate endovascular treatment in a stroke of known onset between 6 and 24 hours.

Contrast-induced nephropathy: A dilemma between loss of neurons or nephrons in the setting of endovascular treatment of acute ischemic stroke.

PURPOSE: The aim is to report the incidence and risk factors of contrast-induced nephropathy after the use of iodine-based contrast for the endovascular treatment of acute ischemic stroke. METHODS: Data from patients who underwent neuroendovascular procedures in a center over a period of 22 months were analysed retrospectively. Contrast-induced nephropathy was determined by an increase in serum creatinine level of >25% of baseline or an absolute increase in serum creatinine level of at least 44 µmol/L (0.50 mg/dL) occurring after intravascular administration of contrast media without alternative explanation. The primary outcome measure of this study was the presence of contrast-induced nephropathy in these treated patients. Continuous data were presented as mean ± standard deviation, and categorical data as frequencies or percentages. The comparison was made using Student's t-test or Fisher's test. Logistic regression was performed to find independent contrast-induced nephropathy predictors. All statistical analyses were performed using Microsoft Excel. A p value of less than 0.05 was considered statistically significant. RESULTS: One hundred and eighty-nine patients undergoing endovascular treatment for acute ischemic stroke. Twenty cases of the total cohort (n = 189) presented contrast-induced nephropathy (10.58%). Only diabetes and creatinine levels between 1.3 and 2.5 mg/dL were associated with contrast-induced nephropathy. No patient was treated with dialysis. CONCLUSION: Contrast-induced nephropathy is a relatively common complication after endovascular treatment of acute ischemic stroke and is associated with worse outcome in patients with this condition. However, there is no increase in the frequency of hemodialysis after the use of iodinated contrast medium.

Endovascular treatment of stroke in children under 2 years with heart failure and ventricular assist device.

INTRODUCTION: Strokes in children are characterised by a high mortality rate while, at the same time, the low number of cases makes it difficult to gain practical experience. As heart disease is the most common risk factor, and as more and more cardiological interventions are being carried out, an increase in the incidence of paediatric stroke is expected. In some cases a transplant is required. While waiting for a donor, the use of ventricular assist devices may be necessary. These present with a high rate of neurological complications. We present two cases of children under 2 years of age awaiting heart transplantation supported by ventricular assist devices who had a stroke which was treated by endovascular techniques. Case 1: A 16-month-old boy with restrictive cardiomyopathy who was listed for a cardiac transplant. At 20 months he required an implantation of an external biventricular support device (Berlin Heart) and had a left hemisphere stroke at 23 months. An intra-arterial approach was used and produced good clinical results. One month later, a heart transplant was performed successfully. Case 2: An 18-month-old girl with non-compacted dilated cardiomyopathy included in the cardiac transplant programme and in need of a Levitronix Centrimag ventricular assist device presented with an acute left hemisphere stroke at 23 months. An intra-arterial procedure was carried out leading to positive clinical results except for residual right hypertonia. Seven months later she received her transplant. CONCLUSION: As a result of the difficulty in performing arterial puncture, the small vessel calibre and the limitation in the use of iodated contrast, there are certain limitations to endovascular treatment of strokes in children that can lead to complications. A multidisciplinary approach to managing such cases would be helpful.