7.1 Introduction

Flow diversion has been successfully applied to the treatment of large, wide-necked aneurysms; dissecting aneurysms; and small blood blister aneurysms whose morphology is not amenable to conventional endosaccular aneurysm occlusion. ¹ , ² , ³ Although the Pipeline Embolization Device (PED; Covidien, Irvine, CA) is the only flow-diverting stent approved for use by the U.S. Food and Drug Administration, other commercially available flow diverters include the SILK device (Balt Extrusion, Montmorency, France), Flow Redirection Endoluminal Device (FRED; MicroVention, Tustin, CA), Surpass (Stryker, Kalamazoo, MI), and p64 (Phenox, Bochum, Germany). These stents are self-expandable, endoluminal devices that disrupt pulsatile blood flow within an aneurysm. By altering the physiologic blood flow, these devices lead to thrombosis of the aneurysm and parent vessel reconstruction. ³ , ⁴

The application of flow diversion in the setting of acute subarachnoid hemorrhage (SAH) is controversial because of three major limitations: requirement of dual-antiplatelet therapy, delayed aneurysm occlusion, and the potential for additional invasive procedures (ventriculostomy, ventriculoperitoneal shunt, decompressive craniectomy, tracheostomy, etc.). As a result, their use has only been described in a few small case series centered on ruptured dissecting aneurysms and ruptured blood blister aneurysms. ¹ , ³ , ⁵ , ⁶ Additionally, variations in practice regimens in the selection of antiplatelet drugs, their dosing, and duration of therapy add another level of complexity to flow diversion treatment of ruptured aneurysms. ⁷

7.2 Patient Selection

The decision to use flow diverters in the setting of acute SAH should be centered on the anatomy of the aneurysm, the condition of the patient, and the comfort level of the neurointerventionalist with flow diverters.

Flow-diverting stents can be considered in cases of morphologically challenging aneurysms such as small blister-type aneurysms, fragile walled dissecting aneurysms, and large wide-necked aneurysms. ¹ , ³ , ⁵ , ⁶ , ⁸ , ⁹ , ¹⁰ , ¹¹ , ¹² , ¹³ In these select cases, endoluminal therapy with flow diverters can lead to improved neck and parent vessel reconstruction without the added risk of manipulating the aneurysm sac in the immediate postrupture period.

The clinical grade and condition of the patient need to be taken into account because these will determine the potential need for further surgical intervention. Favorable patients include those with low Hunt-Hess and Fisher′s grades who do not have hydrocephalus and those who present days after the initial rupture. ⁵ , ¹⁴ Patients who present in poor clinical condition generally require additional intracranial procedures such as external ventricular drains (EVDs), ventriculoperitoneal shunts/lumboperitoneal shunts (VPS/LPS), as well as feeding tubes and tracheostomies. These patients are at risk for EVD- or VPS-related tract hemorrhages after initiation of antiplatelet therapy. ⁵ , ¹⁵ , ¹⁶ Additionally, these patients are at a higher risk of symptomatic vasospasm that could potentially necessitate treatments for ischemic strokes. ¹⁴ In these high-risk patients, flow diversion may not be ideal because of the need to discontinue and reverse the effects of the antiplatelet agents for surgical interventions while placing the patient at risk for in-stent thrombosis in the immediate postsurgical period.

7.3 Antiplatelet Therapy Management

Evidence regarding antiplatelet therapy during flow diversion is largely based on the cardiac literature and data from stent-assisted coiling of ruptured aneurysms. ¹⁷ , ¹⁸ , ¹⁹ , ²⁰ , ²¹ The common practice is to maintain patients on both aspirin and clopidogrel following stent placement. In the setting of SAH, physicians may modify and vary their regimens after evaluating the risk– benefit profile of potential hemorrhagic and thromboembolic complications associated with antiplatelet medications in the immediate aneurysm postrupture period. As a result, there are heterogeneous practice patterns with antiplatelet medications, their dosing, and duration of use in the setting of ruptured aneurysms. ⁷

Pretreatment. Reports on stent-assisted coil embolization using the Neuroform (Boston Scientific, Fremont, CA) and Enterprise (Codman & Shurtleff Inc, Raynham, MA) stents suggest that antiplatelet medications can be initiated in the acute and subacute period of aneurysm rupture with acceptable complication rates. ¹⁰ , ¹³ , ²² , ²³ , ²⁴ Interventional cardiology studies have shown that a 600-mg loading dose of clopidogrel inhibits platelet aggregation by 55 to 59% within 4 hours of administration and results in platelet inhibition for up to 48 hours. ²⁵ The most common pretreatment regimen in the setting of acute SAH has evolved to aspirin 325 or 650 mg and clopidogrel 600 mg. ⁵ , ⁷ , ⁸ , ¹² , ¹⁴ Patients are usually loaded with both antiplatelet agents at least 24 to 72 hours before intervention. ¹ , ⁸ , ¹²

Posttreatment. The appropriate duration of antiplatelets remains controversial. Early withdrawal of antiplatelet medications has been associated with late in-stent PED thrombosis and delayed thromboembolic events. ¹⁷ , ²⁶ At the same time, prolonged dual-antiplatelet use theoretically delays aneurysm thrombosis and exclusion from the circulation. From the literature, the most common practice in the setting of a ruptured aneurysm is to continue the patient on both aspirin and clopidogrel for 6 months postoperatively. The most common doses reported in the literature is clopidogrel 75 mg daily and either aspirin 81 or 325 mg. ⁵ , ⁸ , ¹² , ¹³ , ¹⁴ , ²⁷ The decision to discontinue clopidogrel is usually at the discretion of the neurointerventionalists and results of 6-month follow-up angiography. ¹⁴ Some reports of delayed thromboembolic events argue for prolonged use of longer than 1 year of dual-antiplatelet therapy. ²⁶ , ²⁸ , ²⁹ The reported rate of delayed thromboembolic events after Neuroform stent-assisted coiling is 4.6 to 8.8%. ²⁶ , ³⁰ , ³¹ , ³² This risk needs to be weighed with the risk of delayed aneurysm rupture when the aneurysm is not fully excluded from the circulation. ³³

7.4 Delayed Aneurysm Occlusion/Angiographic Outcomes

Unlike coil embolization, flow diversion may not lead to immediate aneurysm occlusion but rather gradual aneurysm thrombosis over days to weeks. ⁵ , ³⁴ One case series using the PED to treat three ruptured blister aneurysms demonstrated complete aneurysm occlusion immediately in one case and at 6 weeks of angiographic follow-up on two additional cases. ⁵ However, there are no large series that document immediate angiographic cure of ruptured aneurysms with the use of flow diverters. In the case of a ruptured aneurysm, the risk of re-rupture remains and could be exacerbated while the patient is maintained on dual-antiplatelet therapy. Furthermore, this risk may be increased if the patient requires hypertensive therapy for clinically symptomatic vasospasm. Although studies show that there is no added risk of rupture with unruptured aneurysms during the treatment of cerebral vasospasm, the effect on an unsecured ruptured aneurysm with dual-antiplatelet therapy remains unknown. ²⁰ , ³⁵

Several case series investigating the use of flow-diverting stents in unruptured aneurysms report a 95% occlusion rate at 6 to 18 months of follow-up. ² , ²⁹ , ³⁶ , ³⁷ There are limited data on aneurysm occlusion rates with flow diverters in the setting of SAH because of the risk of complications with antiplatelet therapy. Nevertheless, there are several moderate-sized case series investigating the utility of flow diversion in the treatment of ruptured blister aneurysms, dissecting, and giant wide-necked aneurysms ( Table 7.1). A U.S. multicenter investigation utilizing the PED for treatment of 26 ruptured intracranial aneurysms reported a 70% complete occlusion rate at 6 months. ¹² A similar Canadian multicenter investigation using the PED to treat 20 ruptured aneurysms found complete occlusion rates of 75 and 94% at 6 and 12 months, respectively. ¹⁴ Another case series of 11 patients with SAH treated with the PED found a complete occlusion rate of 73% at 6 months. ³⁸ Finally, a case series of 23 patients with dissecting aneurysms reported an occlusion rate of 69.5% at 6 months. ¹

In aneurysms amenable to the placement of coils, coil embolization and flow diversion may be more suitable than using a flow diverter as a stand-alone construct. The placement of coils may afford additional protection to the dome of the aneurysm and may also provide a more thrombotic microenvironment than flow diversion alone.