Neuro-Interventional Use Of Antiplatelets

1. Neuro-
Interventional Use
Of Antiplatelets
Mohamed M.A. Zaitoun, MD
Associate Professor of Interventional Radiology
Faculty of Medicine, Zagazig University, Egypt
FINR-Switzerland
zaitoun2015@gmail.com

2. Disclosure
I have no actual or potential conflict of interest in relation to
this presentation.

3. Agenda
Introduction
Platelet physiology
Antiplatelets medications
Antiplatelets as prophylaxis for neurointerventions
Antiplatelets as rescue therapies
Antiplatelet therapy protocols
Recommendations

4. Introduction
Since the publication of the ISAT trial, the endovascular
approach has progressively become the first line
treatment approach for many aneurysm subtypes.
More recently, endovascular techniques have been
expanded to include balloon and stent-assistance, flow
diversion and individualized endovascular occlusion
devices to widen the treatment spectrum for more
complex aneurysm morphologies.
Pearce S, Maingard JT, Kuan Kok H, et al. Antiplatelet Drugs for Neurointerventions: Part 2 Clinical Applications. Clin Neuroradiol.
2021;31(3):545-558.

5. Endovascular aneurysm treatment has an overall
complication rate of 4.96% with ischemic complications
being the most common (2.82%) and hemorrhagic
complications occurring less frequently (0.90%).
Also after successful recanalization of acute ischemic stroke
using mechanical thrombectomy, approximately 2%-20% of
patients undergo reocclusion, which leads to an
unfavorable prognosis.
Marto J. P., Strambo D., Hajdu S. D., et al. Twenty-four-hour reocclusion after successful mechanical
thrombectomy. Stroke. 2019;50(10):2960–2963.

6. Antiplatelet agents are an effective way to reduce the risk
of ischemic complications during and after
neurointerventional procedures either for prevention or
treatment of thromboembolic complications during
stenting.
Antiplatelet medications vary widely, acting on separate
platelet receptors with different pharmacodynamic and
pharmacokinetic properties.
Wareham J, Flood R, Phan K, Crossley R, Mortimer A. A systematic review and meta-analysis of observational evidence for the use
of bailout self-expandable stents following failed anterior circulation stroke thrombectomy. J Neurointervent Surg. 2019;11:6

7. We will focus on basic platelet physiology, the
pharmacology of common antiplatelet medications
relevant to the practicing interventionist, also will discuss
the clinical applications and evidence-based therapeutic
regimens.

8. Platelet Physiology
Platelets are blood components 2-3μm in diameter, whose
primary function is to initiate the coagulation cascade and
ultimately achieve hemostasis.
Vinik AI, Erbas T, Park TS, Nolan R, Pittenger GL. Platelet dysfunction in type 2 diabetes. Diabetes Care. 2001;24:1476–85.

9. Platelets initiate primary hemostasis
by adhering to themselves and to
damaged vascular endothelium.
Adhesion of platelets to proteins
(collagen, von Willebrand factor),
particularly under conditions of
high shear stress, and the action of
platelet agonists (adrenaline,
thrombin, ADP, thromboxane A2)
leads to the mobilisation of calcium
ion (Ca++), which functions as a
mediator of platelet activation.
P2Y12, an ADP specific receptor, is
present on the platelet membrane,
is coupled to inhibitory G-proteins
and mediates ADP-induced release
of calcium, inhibiting adenylate
cyclase and causing expression of
GPIIb/IIIa receptors, which leads to
platelet aggregation.
Hankey, G.J. and Eikelboom, J.W. (2003), Antiplatelet drugs. Medical Journal of Australia, 178: 568-574.

10. Aspirin inhibits thromboxane A2
synthesis by irreversibly acetylating
cyclooxygenase-1.
The thienopyridines (clopidogrel,
ticlopidine, prasugrel) irreversibly
block the ADP receptor.
Phosphodiesterase inhibitors
(dipyridamole, cilostazol) elevate
intracellular cyclic AMP levels and
thereby inhibit platelet function.
Glycoprotein IIb/IIIa inhibitors block the
final common pathway of platelet
activation leading to fibrinogen
cross-linking of platelets and platelet
aggregation.
Protease-activated receptor-1 (PAR 1)
antagonists (Vorapaxar) have an
antiplatelet effect by inhibiting thrombin-
related platelet aggregation.
Antiplatelets medications
Pearce S, Maingard JT, Li K, et al. Antiplatelet Drugs for Neurointerventions: Part 1 Clinical
Pharmacology. Clin Neuroradiol. 2020;30(3):425-433.

11. 2-P2Y12 Inhibitors
3-Phosphodiesterase (PDE) Inhibitors
4-Glycoprotein IIb/IIIa Agents
1-COX -1 Inhibitors
5-PARS agonists
There is currently limited evidence for these agent’s effectiveness in a neurointerventional setting.

12. Antiplatelets as prophylaxis for neurointerventions
Aspirin single agent therapy
Clopidogrel and Aspirin
Prasugrel and Aspirin
Ticagrelor and Aspirin
Cangrelor

13. Aspirin Single Agent Therapy
Commonly used as prophylaxis in most patients undergoing
elective neurointerventions unless contraindicated.
As many neurointerventional procedures require emergent
management in often complex clinical situations, patients
are not always amenable to oral, nasogastric or rectal
aspirin, in addition to being a relatively simple method of
administration, intravenous aspirin can reduce platelet
aggregation and thromboxane B2 synthesis up to four
times faster than oral formulations.
Zeymer U, Hohlfeld T, Vom Dahl J, Erbel R, Münzel T, Zahn R, Roitenberg A, Breitenstein S, Pap ÁF, Trenk D. Prospective,
randomised trial of the time dependent antiplatelet effects of 500 mg and 250 mg acetylsalicylic acid i. v. and 300 mg p. o. in ACS
(ACUTE). Thromb Haemost. 2017;117(03):625–35.

14. Meta-analysis, to identify any protective effects of antiplatelet
therapy use before coiling of unruptured aneurysms.
2486 patients.
Patients undergoing endovascular coiling for intracranial
aneurysms treated with 100mg of aspirin daily showed lower
rates of thromboembolic (TE) complications than controls,
however, TE complications in the aspirin only group were
higher than in the dual antiplatelet (DAPT) groups.

15. Clopidogrel and Aspirin
Clopidogrel in combination with aspirin as dual antiplatelet
therapy (DAPT) is routinely used in many centers prior to
endovascular aneurysm treatment.
There have been conflicting studies describing a rebound
effect of increased TE risk upon ceasing antiplatelets,
probably due to withdrawal of antiplatelet protection in
patients already at high risk, many centers routinely
maintain patients on aspirin monotherapy following
treatment.
Diehl P, Halscheid C, Olivier C, Helbing T, Bode C, Moser M. Discontinuation of long term clopidogrel therapy induces platelet
rebound hyperaggregability between 2 and 6 weeks post cessation. Clin Res Cardiol. 2011;100(9):765–71.

17. Prasugrel and Aspirin
Recently, the newer antiplatelet agent prasugrel has been used
for patients who are known or suspected to be
nonresponders to conventional agents such as clopidogrel.
It is routinely used in interventional cardiology procedures with
more recent data suggesting efficacy for neurointerventional
procedures.
Schulz S, Angiolillo DJ, Antoniucci D, Bernlochner I, Hamm C, Jaitner J, Laugwitz KL, Mayer K, von Merzljak B, Morath T,
Neumann FJ, Richardt G, Ruf J, Schömig G, Schühlen H, Schunkert H, Kastrati A; Intracoronary Stenting and
Antithrombotic Regimen: Rapid Early Action for Coronary Treatment (ISAR-REACT) 5 Trial Investigators. Randomized
comparison of ticagrelor versus prasugrel in patients with acute coronary syndrome and planned invasive strategy--
design and rationale of the iNtracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary
Treatment (ISAR-REACT) 5 trial. J Cardiovasc Transl Res. 2014;7(1):91–100.

19. Ticagrelor and Aspirin
Has clinical utility in patients who are clopidogrel non-
responders.
The prevalence of ticagrelor hyporesponsiveness appears to be
extremely low.
Hanel RA, Taussky P, Dixon T, et al. Safety and efficacy of ticagrelor for neuroendovascular procedures: a single-center initial
experience. J Neuronterv Surg 2014;6:320–22.
Pearce S, Maingard JT, Kuan Kok H, et al. Antiplatelet Drugs for Neurointerventions: Part 2 Clinical Applications. Clin Neuroradiol.
2021;31(3):545-558.

21. Cangrelor
Evidence for the use of cangrelor in neurointerventional
procedures is limited; however, observational studies
show promise for patients with high risk of hemorrhagic
complications, or in patients who require high-risk
procedures.
Pearce S, Maingard JT, Kuan Kok H, et al. Antiplatelet Drugs for Neurointerventions: Part 2 Clinical Applications. Clin Neuroradiol.
2021;31(3):545-558.

22. Aim to evaluate the safety and effectiveness of IV cangrelor in
neurovascular intervention.
66 patients.
Cangrelor has been found to be an effective antiplatelet for the
treatment of ruptured and unruptured aneurysm with a
hemorrhagic complication rate of 4.2%, it allows the possibility
for a secure transition to long-term ticagrelor and progression
to surgery in the setting of unexpected complications.

23. Antiplatelets as rescue therapies
Abciximab
Eptifibatide
Tirofiban

24. Examined outcomes for patients receiving endovascular coiling for ruptured
and unruptured aneurysms requiring rescue therapy, defined as
treatment with GpIIb/IIIa inhibitors and fibrinolytic therapy.
3 groups: (1) patients receiving GpIIb/IIIa inhibitors only, (2) patients
receiving fibrinolytic therapy only, and (3) patients receiving both
GpIIb/IIIa inhibitors and fibrinolytics.
Glycoprotein (GP) IIb/IIIa inhibitors appeared effective, with better safety
than fibrinolytic agents, those patients treated with GP IIb/IIIa inhibitors
had both lower perioperative morbidity from stroke and lower long-term
morbidity compared with patients treated with thrombolytics.
Furthermore, recanalization rates were nominally higher with GP IIb/IIIa
inhibitors compared with fibrinolytics.

25. Meta-analysis, 23 studies, 516 patients.
Patients receiving GP IIb/IIIa inhibitors had significantly lower perioperative
morbidity from stroke/hemorrhage compared with those treated with
fibrinolytics, and were significantly less likely to have long-term morbidity.
There was a trend toward higher recanalization rates among patients treated
with glycoprotein IIb/IIIa inhibitors compared with those treated with
fibrinolytics.
Patients receiving tirofiban or eptifibatide had significantly higher
recanalization rates compared with those treated with abciximab.
No difference in recanalization was seen in patients receiving intra-arterial or
intravenous GP IIb/IIIa inhibitors.

26. Abciximab
Abciximab is used as a rescue therapy for intraprocedural
thrombus formation during intracranial aneurysm coiling.
For treatment of intraprocedural thrombus formation boluses of
4-10mg were sufficient to remove thrombus from either the
instrument or coil protruding into the parent artery with no
increased risk of hemorrhagic complications.
Ries T, Siemonsen S, Grzyska U, Zeumer H, Fiehler J. Abciximab is a safe rescue therapy in thromboembolic events complicating cerebral
aneurysm coil embolization: single center experience in 42 cases and review of the literature. Stroke. 2009;40(5):1750–7.

28. 2004

29. Eptifibatide
Eptifibatide appears to be useful for proximal thrombus or
in-stent occlusions during aneurysm coil embolization but
may be less useful for distal thrombi.
Eptifibatide may also be an effective prophylactic measure
for intraprocedural thrombus.
Sedat J, Chau Y, Mondot L, Chemla R, Lonjon M, Padovani B. Is eptifibatide a safe and effective rescue therapy in thromboembolic
events complicating cerebral aneurysm coil embolization? Singlecenter experience in 42 cases and review of the literature.
Neuroradiology. 2014;56(2):145–53

32. Tirofiban
Several studies have examined the use of tirofiban in
neurointerventional procedures.
Jeong HW, Jin SC. Intra-arterial infusion of a glycoprotein IIb/IIIa antagonist for the treatment of thromboembolism during coil
embolization of intracranial aneurysm: a comparison of abciximab and tirofiban. AJNR Am J Neuroradiol. 2013;34(8):1621–5.

35. Antiplatelet Therapy Protocols
antiplatelet regimens where DAPT is indicated (i.e. flow diversion)

36. Recommendations
Combination DAPT appears superior to monotherapy
following the placement of flow-diverting stents and
following aneurysm coiling.
Ticagrelor and low dose prasugrel may provide better
protection against thrombotic complications than
clopidogrel for thrombosis prophylaxis in flow diverting
stents.
In comparison to abciximab, tirofiban and eptifibatide
appear to be safer in relation to reduced TE and
hemorrhagic complications when used as a rescue
therapy.