Drug-Coated Balloon Treatment for Delayed Recanalization of Symptomatic Intracranial Artery Occlusion

We retrospectively reviewed our prospective stroke database to identify consecutive patients with symptomatic non-acute ICAO who were treated with DCBs from January 2015 to July 2021. Informed consent was obtained from all patients or their authorized family members before surgery, and the study was approved by our institutional review board and complied with the Declaration of Helsinki.

ICAO was diagnosed using CT angiography (CTA) or magnetic resonance angiography (MRA) and confirmed by digital subtraction angiography (DSA) for all patients. The duration of occlusion was defined as the time from initial radiological diagnosis to endovascular treatment. The following inclusion criteria were used: (1) duration of occlusion > 24 h; (2) intracranial atherosclerosis was the primary etiology; (3) recurrent transient ischemic attacks (TIA) or stroke related to an occluded intracranial artery despite optimal medical treatment, which was defined as treatment that included DAPT, statin, blood pressure and glucose control, smoking cessation, and an emphasis on a healthy lifestyle; and (4) hemodynamic failure and hypoperfusion in the target artery territory were confirmed based on clinical and imaging evidence (the symptoms were triggered or exacerbated by orthostatism or lower blood pressure, and relatively small and multiple infarctions on diffusion-weighted imaging (DWI) with a large area of low perfusion assessed using arterial spin labeling (ASL), which demonstrated hypoperfusion defects in the target territory of these patients). The following exclusion criteria were used: (1) nonatherosclerotic diseases, such as suspected cerebral vasculitis, arterial dissection, and potential source of cardiac embolism; (2) clinical symptoms were stable with optimal medical treatment; (3) concomitant with intracranial aneurysms and any bleeding disorder; (4) life expectancy < 1 year due to other medical conditions; and (5) contraindications to surgery, such as known allergy or contraindication to aspirin, clopidogrel, or anesthesia.

DAPT with 100 mg aspirin and 75 mg clopidogrel daily was given at least 5 days before the procedure. Thromboelastography platelet mapping was performed to guide the modulation of antiplatelet treatment. The endovascular procedures were performed under general anesthesia. The details of the procedure were described previously [12‐14]. Adequate predilation using conventional balloons (Gateway; Boston Scientific, USA) was mandatory before DCB. DCB (SeQuent Please; B. Braun, Germany) dilation was only performed when the residual stenosis was not greater than 50% or there was no dissection after predilation. The diameter of the DCB corresponded to approximately 80 to 100% of the diameter of the normal vessel and was 0.5 to 1 mm larger than the conventional balloon. The DCB covered the entire lesion and was slowly inflated at a nominal pressure for 60 s to transit the paclitaxel into the vessel wall. After withdrawal of the DCB, an angiogram was reperformed to evaluate the lumen and exclude vessel dissection, perforation, and distal embolization (Fig. 1). If the residual stenosis was > 50% or there was vessel dissection after DCB dilation, remedial stenting implantation was performed (Fig. 2). The choice of stent (self-expanding or balloon-mounted stent) and the use of glycoprotein IIb/IIIa inhibitors were left to the surgeon’s discretion. Post-procedural antegrade flow was graded using the TICI grading system, and technical success was determined by recanalization with a TICI grade 2b on post-procedural angiography. DAPT was maintained for 3 months for patients with only DCB dilation and 6 months for patients with remedial stenting implantation. Aspirin or clopidogrel monotherapy was maintained thereafter.

Bild vergrößern

Bild vergrößern

Demographic, clinical, angiographic, and periprocedural data were collected. The baseline modified Rankin Scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS) were used before the procedure. The Alberta Stroke Program Early CT score (ASPECTS) for anterior circulation and posterior circulation acute stroke prognosis early CT score (pc-ASPECTS) for posterior circulation on the last DWI before the procedure were assessed by well-trained neurologists. The patients were scheduled to return for an angiographic examination 6 months (± 1 month) after the index procedure. The primary outcome within 30 days was any stroke (including ischemic or hemorrhagic stroke), TIA, and death after the procedure. The primary outcomes beyond 30 days were ischemic stroke within the territory of the target vessel, TIA within the territory of the target vessel, hemorrhagic stroke, rate of restenosis, and death attributed to stroke during the follow-up post-index procedure.

Restenosis was defined as > 50% stenosis within or immediately adjacent (within 5 mm) to the treated segment and > 20% absolute luminal loss. Symptomatic restenosis was defined as restenosis associated with ischemic symptoms of the offending vessel territory. Two investigators reviewed imaging and clinical outcomes. Disagreements were resolved via consensus.

Continuous data are expressed as the means ± SD or as the medians with interquartile range (IQR), and categorical data are presented as numbers and percentages. All statistical analyses were performed using SPSS version 22.0 for Windows (IBM, Armonk, New York, USA).

The 30-day outcome rate was 8.8% (13/148; Table 2). Ischemic stroke occurred in 5 patients (3.4%), and all strokes were related to the target territory. Three patients presented with perforator ischemic stroke related to the basilar artery territory, 1 patient presented with perforator ischemic stroke related to the intracranial vertebral artery territory, and embolization occurred in 1 patient related to the intracranial carotid territory. Hemorrhagic stroke occurred in 5 patients (3.4%), and all cases were related to the target middle cerebral artery territory, which resulted from hyperperfusion after recanalization. Death occurred in 3 patients (2.0%), and all 3 deaths were attributed to hyperperfusion after target lesion recanalization (2 lesions in the middle cerebral artery and 1 lesion in the basilar artery).

Clinical and angiographic follow-up outcomes of the patients beyond 30 days are presented in Table 2. During the 25.8 ± 15.8-month clinical follow-up period, the rate of outcome beyond 30 days was 4.7% (7/148).

Ischemic stroke occurred in 4 patients (2.7%), and TIA occurred in 2 patients (1.4%). All 6 of these patients had imaging follow-up, and they all had target lesion restenosis. Hemorrhagic stroke occurred in 1 patient (0.7%). There was no death attributed to stroke during the follow-up period. During the 4.9 ± 2.4-month vessel imaging follow-up period, DSA was obtained for 55 patients, MRA was obtained for 7 patients, and CTA was obtained for 4 patients. Restenosis occurred in 9 patients (9/66, 13.6%) who had follow-up imaging: 6 patients presented with angiographic symptomatic restenosis, and the other 3 patients presented with asymptomatic restenosis.

This study has some limitations. First, this study was a retrospective cohort study. Second, this study was a single-center study, and the choice of treatment method was based on patient preference and surgeon experience, which may lead to selection bias. Third, this study did not have a control group. We will compare DCB treatment with conventional balloon dilatation/stenting or no endovascular treatment in the future.