Commentary: Antiplatelet Therapy in Flow Diversion

In this paper,1 the authors review the literature regarding the most common platelet-inhibiting regimens used to prevent thromboembolic complications during and after flow diversion procedures for intracranial aneurysms. The article provides a succinct description of the mechanism of action for the various antiplatelet agents and expands on the literature regarding ex-vivo P2Y12 inhibitor activity testing. Furthermore, the authors touch on the considerations pertaining to antiplatelet therapy for ruptured intracranial aneurysms. The review is very well-written and provides a good overview of the current concepts. We would like to address a few additional points that we feel deserve the reader's attention. Flow diversion stents have a denser metal surface-coverage area than conventional intracranial stents (30% vs 10%), in order to divert flow away from the aneurysm and induce thrombosis. At the same time, this porosity allows for keeping open branch vessels and perforating arteries that are crossed by the device.2 Importantly, close attention to antiplatelet therapy is a key reason that has made this procedure safe in cases where perforator branches and bifurcation vessels are covered by the device. Thrombus can form within the device and occlude the perforator or bifurcation branches, recanalize and cause periprocedural or delayed hemorrhage. This process can be prevented using an effective antiplatelet regimen before, during, and after the procedure. A pooled data analysis of 2002 patients by Saber et al in 20193 did not show significant difference in hemorrhagic complications among different antiplatelet regimens, but no study to the authors’ knowledge has targeted this comparison specifically in flow diversion cases covering bifurcation and perforator branches. Several studies have foregone the use of platelet function testing (PFT), and a number of centers do not utilize PFTs routinely in the setting of flow diversion. Several arguments could be made regarding whether routine PFT is actually needed. As the authors note, the PUFS trial was performed without PFTs and had fairly low complication rates, which is used as an argument that PFTs are not indicated for flow diversion. Furthermore, in the field of cardiology, ticagrelor is now considered the first-line agent, instead of clopidogrel, making PFTs obsolete. However, in neurovascular interventions, ticagrelor has not yet been conclusively shown to be better than clopidogrel as the baseline agent. Since clopidogrel is still the first-line agent, and there is such high variability in response rates, we would argue that PFTs are strongly indicated with the current standard protocols. In our experience, clopidogrel response testing and switching to ticagrelor where appropriate is important for flow diversion procedures. In a multicenter retrospective cohort by Adeeb et al4 in 2017, the authors studied 414 pipeline embolization procedures. Thromboembolic complications occurred in 9.2% of those and were symptomatic in 5.6%. Importantly, clopidogrel nonresponders had a significantly higher rate of thromboembolic complications compared to clopidogrel responders (17.4% vs 5.6%). Nonresponders who were switched to ticagrelor had significantly lower risk (2.7% vs 24.4%). Standardizing PFT has been difficult because of the high variability of these methods between laboratories, and the weak correlation noted between different testing modalities.5 We feel that these assays should be standardized for flow diversion interventions, and used in all occasions that clopidogrel is given as a first-line agent. Antiplatelet therapy for flow diversion in ruptured aneurysms is a topic without a plethora of data. Cangrelor has been suggested as a novel IV agent, and may have its merits, especially due to its short half-life and duration of action.6,7 Furthermore, while it would be hard for ticagrelor to replace clopidogrel as the first-line agent for unruptured aneurysms receiving flow diversion due to its cost and similar outcomes,8 a case could likely be made for using ticagrelor first-line for ruptured aneurysms requiring emergent flow diversion. These patients may not have enough time before the procedure for formal PFTs to check for clopidogrel response reliably. In conclusion, there remain multiple areas that need to be further studied and clarified regarding antiplatelet management for flow diversion. We congratulate the authors for their thorough contribution, piecing together the scant data that exists for several of these questions. We believe there is room for further research, especially in the areas of standardizing antiplatelet regimens, PFT and antiplatelet regimens for flow diversion in ruptured aneurysms. Disclosures Dr Thomas is a guest editor of the Flow Diversion for Intracranial Aneurysm Treatment Supplement, and was on the DSMB of the SCENT trial for SURPASS. Outside of publication in this supplement, Dr Maragkos has no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.