**5. Pre-operative preparation**

A baseline neurological examination is performed and neurological scores are attributed when applicable (e.g. modified Rankin and NIHSS score), which are useful for follow-up , especially for patients who have a past history of neurological disease.

Antiplatelet agents are highly recommended in the preparation patients undergoing intracranial stenting. Insufficient platelet inhibition (PI) has been associated with an augmented risk of thrombus formation and embolic complications. As a consequence, patients receive either a loading-dose or a period of antiplatelet therapy. A loading-dose of 300 or 600 mg of clopidogrel is then administered the day before the endovascular treatment. Alternatively a dose of 75mg PO QD for five or more days has also been proposed for some authors. This is supported by both literature to date and previous experience in the cardiology field.

Since double antiaggregation is recommended, administration of acethyl-salicic acid (ASA) is also performed perioperatively. Some authors have suggested the use of preparations of 325mg or more for three or more days before the procedure, concomitant with clopidogrel. Other teams have preferred to administer a single intravenous bolus of 250-500 mg of injectable ASA at the moment of the endovascular procedure. This presents the advantage of avoiding the use of double antiaggregation in the pre-operative period, in which the aneurysm is not yet secured. However, injectable preparations are not available in all countries worldwide.

Whilst ASA resistance seems relatively uncommon, clopidogrel resistance seems to be frequent. The prevalence of low-response to this drug varies from 28% to 66% in literature. Little data is available specifically for patients undergoing stent-assisted treatment of intracranial aneurysms, but thromboembolic adverse events do seem highly concentrated in the low responder group. Some authors have consequently recommended a level of at least 40% of platelet inhibition.

Individual response to clopidogrel may be evaluated using different techniques. Recently, point-of-care assays have been commercially available, allowing practitioners to perform prompt measurements pre-operatively. The level of PI is now routinely assessed before intracranial stenting in a number of centers. In selected cases, the doses of antiplatelet agents might be adapted in order to achieve the desired levels. Another advantage of these pointof-care assays is the fact that they may be performed per-operatively, so that the operator is informed of the percentage of antiaggregation at the moment of stent deployment.

294 Aneurysm

not be feasible.

**5. Pre-operative preparation** 

experience in the cardiology field.

countries worldwide.

40% of platelet inhibition.

The tortuosity of the parent artery and the technique for coiling (e.g. jailing, semi-jailing, 'X' and Y' stents, etc.) also influences the type of stent used (open cell versus closed cell, selfexpandable versus balloon-mounted, etc). It is particularly important to detect potential irregularities due to other vascular pathologies such as atherosclerosis or fibromuscular dysplasia. Part of the assessment of feasibility of the stent-assisted treatment is the study of branches presenting with sharp angle of bifurcation or incorporation of its origin into the neck of the aneurysm. Such vessels may be very difficult to catheterize. If it needs to be stented, this may result in a longer and more laborious procedure. If the progression of a microguidewire and a microcatheter inside a recurrent branch is impossible after numerous attempts, other treatment modalities (e.g. surgical) must be considered. As a consequence, the patient must be properly informed before the endovascular procedure that his or her treatment presents elements of technical complexity, and that endovascular treatment may

A baseline neurological examination is performed and neurological scores are attributed when applicable (e.g. modified Rankin and NIHSS score), which are useful for follow-up ,

Antiplatelet agents are highly recommended in the preparation patients undergoing intracranial stenting. Insufficient platelet inhibition (PI) has been associated with an augmented risk of thrombus formation and embolic complications. As a consequence, patients receive either a loading-dose or a period of antiplatelet therapy. A loading-dose of 300 or 600 mg of clopidogrel is then administered the day before the endovascular treatment. Alternatively a dose of 75mg PO QD for five or more days has also been proposed for some authors. This is supported by both literature to date and previous

Since double antiaggregation is recommended, administration of acethyl-salicic acid (ASA) is also performed perioperatively. Some authors have suggested the use of preparations of 325mg or more for three or more days before the procedure, concomitant with clopidogrel. Other teams have preferred to administer a single intravenous bolus of 250-500 mg of injectable ASA at the moment of the endovascular procedure. This presents the advantage of avoiding the use of double antiaggregation in the pre-operative period, in which the aneurysm is not yet secured. However, injectable preparations are not available in all

Whilst ASA resistance seems relatively uncommon, clopidogrel resistance seems to be frequent. The prevalence of low-response to this drug varies from 28% to 66% in literature. Little data is available specifically for patients undergoing stent-assisted treatment of intracranial aneurysms, but thromboembolic adverse events do seem highly concentrated in the low responder group. Some authors have consequently recommended a level of at least

especially for patients who have a past history of neurological disease.

Such an approach requires systematic blood sampling, subsequent drug administration and financial investment. At present, no prospective study assessed the potential benefits in achieving a level of anti-aggregation over 40% in patients undergoing intracranial procedures. The same applies for the assessment of the risk of hemorrhagic adverse events that may be related to the combination of intravenous heparin and double antiaggregation.

We have witnessed a proliferation of portable devices and this technology is increasingly being used, and particularly in the cardiology field. Different assays are now commercially available: VerifyNow (Accumetrics, San Diego,USA), PlateletWorks (Helena Lab.; Beaumont,USA), IMPACT-R (with and without ADP stimulation, DiaMed AG, Cressier sur Morat,Switzerland), DADE PFA collagen/ADP test (Siemens Healthcare Diagnostics Products, Marburg,Germany) and others. Even so, there is some evidence that only measurements using light transmittance aggregometry (VerifyNow and PlateletWorks) are significantly correlated to the occurrence of ischemic adverse events in interventional cardiology as suggested by the POPULAR study in 2010 (Breet et al., 2010). Other studies, such as the BOCLA (Neubauer et al., 2011), showed that the concept of clopidogrel resistance may be relative, and that more than half of poor responders may have a good response by increasing (two-fold) the dose.

In the field of interventional neuroradiology, studies specifically focused on the importance of antiaggregation are rare. Four case series were published in 2008 (Lee et al., 2008, Muller-Schunk et al., 2008, Pandya et al., 2008, Prabhakaran et al., 2008). Only two have studied the incidence of thromboembolism using techniques and different cut-offs. We recently performed a study on 271 procedures in which the VerifyNow assay was used and observed a significant association between thromboembolism and poor antiagregation. The ability to predict the risk of a thromboembolic event occuring does exist, but it is moderate given the multifactorial nature of these events. In our experience, body weight should be considered as an important factor to observe. After a homogenous, single loading dose of 300mg of clopidogrel, the prevalence of low-response (<40% of PI) is significantly lower in patients weighing less than 60 kilograms (43% versus 29%). If a stent has to be deployed urgently and the patient has not been prepared with antiplatelet agents, the risk of thromboembolic events may be significant, since post-operative aspirin and clopidogrel will take time to act. Some authors have suggested the use of a loading dose just after the procedure. Others have preferred to use a GPIIb/IIIa inhibitor . A bolus of 0.025 mg/Kg of intravenous abciximab may be administered and followed by infusion at 10 mcg/min per 12 hours. Evidently, this strategy should be used with caution and not as routine in view of the well-known hemorrhagic side effects of intravenous GPIIb-IIIa inhibitors.
