Anterior Cerebral Artery (A1 Segment) Aneurysm: Abandoned Dual Platelet Inhibition Shortly After Endovascular Treatment with a Hydrophilic Polymer-Coated Flow Diverter p48_HPC; Good Clinical Outcome and Early Aneurysm Occlusion
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A wide-necked aneurysm originating from the proximal A1 segment of the right-hand side anterior cerebral artery (ACA) of a 33-year-old patient was diagnosed on follow-up MR imaging after the resection of an anaplastic astrocytoma WHO grade III. In order to reconstruct the parent vessel and avoid long-term dual antiplatelet therapy (DAPT), flow diversion was successfully carried out using a p48_HPC. The patient had not shown any focal neurological deficit after his initial treatment 5 years previously.
The current clinical standard stipulates that DAPT be prescribed following the implant of a flow diverter in an intracranial vessel. To this end, ASA and ticagrelor were prescribed for 12 months post procedure. However, the patient intentionally stopped his medication 4 days after discharge and continued only to take phytopharmaceuticals such as garlic and grape seed extract. Regular follow-ups with digital subtraction angiography (DSA) revealed the frequent finding of mild deformations of the ultimately patent flow diverter without any in-stent stenosis. The patient remained asymptomatic at all times after the procedure.
The pharmaceutical regimen after treatment with a coated low-profile flow diverter and its clinical potential in the context of complicating comorbidities are the main topics of this chapter.
KeywordsPlatelet function Antithrombotic coating Flow diversion
A 33-year-old male patient presented to our outpatient clinic after complete recovery from the microsurgical resection and adjuvant, antiproliferative chemotherapy of a right-sided, frontally located anaplastic astrocytoma. Postoperative gene analysis of the neoplasm revealed a partially methylated MGMT (O-6-methylguanine-DNA methyltransferase) promotor (11%), indicating a good response to the alkylating chemoradiotherapy. (MGMT is a DNA repair protein produced by dealkylating guanine. A methylated MGMT promotor causes lower MGMT protein expression, which allows the alkylating chemoradiotherapy to be more effective.) The patient had completed 13 consecutive cycles of chemoradiotherapy at a daily dose of 430 mg temozolomide (Temodal, Merck Sharp & Dohme). During a scheduled, regular follow-up 5 years after the initial anaplastic astrocytoma diagnosis, imaging revealed a broad-based, ipsilateral A1 aneurysm.
The wide neck of the progressively growing aneurysm meant that coil occlusion would be unnecessarily risky. Given the patient’s desire for effective treatment within the shortest possible time frame, it was decided to employ flow diversion, using the most suitable low-profile flow diverter stent (FDS). Because of the recent reappearance of the patient’s anaplastic astrocytoma, potentially requiring open surgery soon, putting the patient under long-term DAPT, as conventionally done with flow diversion, was considered inappropriate. To this end, consent was received to treat the aneurysm with a low-profile flow diverter (p48_HPC), which would require both shorter and lower platelet function inhibition due to the hydrophilic coating of the implant.
Procedure, 28.01.2019: endovascular flow diversion in the anterior cerebral artery in order to treat an A1 saccular aneurysm with a fundus diameter of 7 mm
Anesthesia: general anesthesia; 5,000 IU unfractionated heparin (Heparin-Natrium, B. Braun) IV after securing the femoral access
Premedication: 1× 500 mg ASA and 1× 180 mg ticagrelor (Brilique, AstraZeneca); ongoing medication of 1× 100 mg ASA PO daily and 2× 90 mg ticagrelor PO daily
Access: right common femoral artery, 1× 8F sheath (Terumo); diagnostic catheter: 1× 6F Neuron MAX 088 (Penumbra); guide catheter: 1× 5F vertebral catheter 125 cm (Cordis); distal access catheter: 1× 6F SOFIA 115 cm (MicroVention); microcatheter: 2× Prowler Select Plus (Cerenovus); microguidewire: 1× Traxcess EX 0.014″ 200 cm (MicroVention)
Implant: 1× flow diverter: p48_HPC, 2/15 mm (phenox)
Course of treatment: The guiding catheter and the distal access catheter were inserted into the right ICA. After calibrating the DSA system, the proximal diameter of the right A1 segment was measured as 2.2 mm and the distal diameter as 1.9 mm. The sharp-angled course of the proximal A1 segment required a Prowler Select Plus 45° microcatheter to be combined with a Traxcess EX 0,014″ 200 cm microguidewire to successfully navigate the somewhat challenging passage through the right ACA (A3 segment). Subsequently, the p48_HPC 2/15 mm flow diverter was placed uneventfully within the right A1 segment, carefully avoiding the adjacent right ICA bifurcation and the right-sided AcomA and A1/A2 junction. DSA, after the p48_HPC had been deployed, revealed that the device had not fully unfolded, causing significant stenosis in the proximal third of the right A1 segment. Given the initially challenging catheterization and the current opacification pattern, local vasospasm was considered to be the most likely underlying cause.
Duration: 1st–21st DSA run: 60 min; fluoroscopy time: 17 min
Postmedication: heparinization with a PTT of 50 s for 24 h after the intervention; the intended medication included 1× 100 mg ASA PO daily for life, 2× 90 mg ticagrelor for an indefinite period, at least for 6 months post procedure. However, just 4 days after discharge, the patient intentionally stopped taking the prescribed medication for dual platelet inhibition, preferring instead to take a self-prescribed, purely phytopharmaceutical cocktail exclusively. More specifically, he started with the intake of one clove of freshly dried garlic per day, subsequently switching to 3× 500 mg garlic oil (in capsules) daily. Additionally, he started consuming 3× 500 mg grape seed extract daily in capsules.
General anesthesia was terminated uneventfully immediately after the procedure. During the first 24 h of his stay on the ICU, the patient reported subtle, transient shades in the upper nasal quadrant of the right eye, but no further sequelae were encountered.
NCCT 24 h after the p48_HPC implantation revealed no clinically inapparent, procedure-related complications. The patient was transferred to the neurosurgical ward until discharge at day 5 after the intervention.
MRI 8 days after the intervention showed the morphologically unchanged, right-sided A1-aneurysm. No DWI-positive lesions or other signs of ischemia or hemorrhage were observed in the dependent brain parenchyma.
Radiography was performed 1 month after the procedure and showed dilatation of the device corresponding to the aneurysm-bearing segment of the right ACA, whereas the adjacent middle section of the p48_HPC was moderately narrowed.
The specific anatomical situation at hand, more specifically the acute-angled course of the small A1 segment and the proximally located broad-based aneurysm, demanded a precise and atraumatic catheterization of the target vessel, which can be challenging to perform when using for conventional flow diverter equipment. The latter requires rather stiff delivery catheters with large inner diameters and crossing profiles (e.g., Phenom 27, Medtronic; Excelsior XT-27, Stryker Neurovascular), rendering access to small, distinctly curved vessels risky and technically tricky.
Distally located, wide-necked aneurysms have a propensity to reoccur when employing (stent-assisted) coil occlusion. They are, however, eminently suitable targets for low-profile flow diverter treatment (Iosif and Biondi 2019; Martínez-Galdámez et al. 2019). These new generation devices can be delivered via low-profile microcatheters, for example, the Prowler Select Plus (Cerenovus) or the Headway 17 (MicroVention), thus facilitating a primarily atraumatic catheterization while avoiding potentially critical exchange maneuvers (Schob et al. 2019).
In the patient presented, the comorbidity of a WHO grade III astrocytoma exhibiting recent relapse, which would require open surgery shortly, prohibited the otherwise obligatory long-term DAPT required for conventional flow diverter stents. Therefore, a next-generation device offering efficient one-stage treatment together with the option of reduced platelet function inhibition was chosen.
The p48_HPC is currently the only low-profile flow diverter with a hydrophilic polymer coating, which significantly decreases its thrombogenicity (Lenz-Habijan et al. 2018). More specifically, it was recently demonstrated that the glycan-based hydrophilic coating radically reduces platelet cell agglomeration both in vitro and ex vivo. A controlled, randomized clinical trial for this is, however, still lacking. Flow diversion with single antiplatelet therapy (SAPT) is an on-label procedure with p48_HPC if justified by the clinical circumstances. As a consequence of the circumstances described above, informed patient consent for p48_HPC treatment with optional early SAPT, including unlikely but potentially severe ischemic complications, was obtained. The endovascular treatment implanting the p48_HPC was uneventful. The non-compliant patient decided to terminate DAPT immediately after discharge without consultation and substituted his medication with a cocktail of garlic and grape seed extract, which he had thought out by himself. The patient remained clinically asymptomatic at all times, and regular follow-up imaging revealed a patent FDS without aggravated intimal hyperplasia or in-stent stenosis, while the aneurysm had already been entirely excluded from the circulation within 3 months.
In our experience, ischemic complications are a common issue if DAPT is discontinued after flow diverter implantation. We attribute the implausibly uneventful course of the early postinterventional period after early DAPT termination to the efficacy of the hydrophilic polymer coating of the p48_HPC. However, the phytopharmaceutical medication may also have contributed to this outcome, as a distinct inhibitory effect on platelet function has been described for garlic in high concentrations (Alali et al. 2017; Chang et al. 2004, 2005).
In conclusion, p48_HPC represents a promising low-profile flow diverter for treatment of aneurysms under anatomically difficult circumstances, especially if conventional DAPT cannot be guaranteed for the current period of 12 months. This case report is, however, an anecdotal observation, which requires further corroboration by randomized controlled trials.
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