Dual antiplatelet therapy

Dual antiplatelet therapy

Indications

Adequate dual antiplatelet (AP) therapy is imperative when performing neurovascular stenting procedures.

After stenting, the patient remains on dual antiplatelet therapy (ASA + Plavix) for at least a month and ASA alone indefinitely.

Currently, no consensus for the ideal AP regimen exists.

The most frequent included acetylsalicylic acid (ASA) 325 mg+Plavix 75 mg daily (for 7 days prior) and ASA 325 mg+Plavix 75 mg daily (for 5 days prior) for routine placement of intracranial and cervical stents, respectively. For emergency placement, ASA 325 mg+Plavix 600 mg (at time of surgery) was the most frequently used.

Significant heterogeneity in dual antiplatelet regimens following Pipeline Embolization Device (PED) placement and associated costs, exists at major academic neurovascular centers. The most commonly used first line dual antiplatelet regimen consists of aspirin and clopidogrel. Two major alternate protocols involving ticagrelor and prasugrel, are administered to clopidogrel hypo-responders. The optimal dual antiplatelet regimen for patients with cerebrovascular conditions has not been established, given limited prospective data within the neurointerventional literature 1).

Given its importance, evidence based protocols are imperative. Minimal literature exists focusing on neurovasculature, and therefore understanding current practice patterns represents a first step toward generating these protocols. 2).


Dual antiplatelet therapy (e.g. ASA + Plavix®) are mandatory for 4 weeks (90 days is preferable 3) after placement of a bare metal cardiac stent, and for at least 1 year with drug-eluting stents (DES) (the risk declines from ≈ 6% to ≈ 3%) 4). Even short gaps in drug therapy (e.g. to perform neurosurgical procedures) is associated with significant risk of acute stent occlusion (and therefore elective surgery during this time is discouraged 5) DES is so effective in suppressing endothelialization that lifetime dual antiplatelet therapy may be required. Bridging DES patients with antithrombin, anticoagulants, or glycoprotein IIb/IIIa agents has not been proven effective 6).

Antiplatelet Therapy in Flow Diversion

Complications

Dual antiplatelet therapy is associated with high early risks of major and gastrointestinal bleeding that decline after the first month in trial cohorts 7).

Case reports

Ravina et al., presented in 2018 a literature review and an illustrative case of an 18-year-old man who presented with progressive headaches and was found to have a large, unruptured basilar apex aneurysm involving the origins of bilateral superior cerebellar artery and posterior cerebral artery. Given the small posterior communicating artery and complexity of the aneurysm, proximal basilar artery occlusion with unilateral superficial temporal artery-to-superior cerebellar artery bypass was recommended. Despite antiplatelet treatment with acetylsalicylic acid pre- and postoperatively, the patient developed acute ischemia of the brainstem and cerebellum as well as an embolic left temporal lobe infarct. The patient received dual antiplatelet therapy starting postoperative day 6 following which he experienced no new infarcts and made a significant neurologic recovery. The current evidence suggests that proximal BA occlusion in complex BA apex aneurysm cases is thrombogenic and can be especially dangerous if thrombosis occurs suddenly in aneurysms without pre-existing intraluminal thrombus. Dual antiplatelet therapy during the first postoperative week presents a possible strategy for reducing the risk of ischemia due to sudden aneurysm thrombosis 8).

References

1)

Gupta R, Moore JM, Griessenauer CJ, Adeeb N, Patel AS, Youn R, Poliskey K, Thomas AJ, Ogilvy CS. Assessment of Dual Antiplatelet Regimen for Pipeline Embolization Device Placement: A Survey of Major Academic Neurovascular Centers in the United States. World Neurosurg. 2016 Sep 15. pii: S1878-8750(16)30839-7. doi: 10.1016/j.wneu.2016.09.013. [Epub ahead of print] PubMed PMID: 27641263.
2)

Faught RW, Satti SR, Hurst RW, Pukenas BA, Smith MJ. Heterogeneous practice patterns regarding antiplatelet medications for neuroendovascular stenting in the USA: a multicenter survey. J Neurointerv Surg. 2014 Jan 3. doi: 10.1136/neurintsurg-2013-010954. [Epub ahead of print] PubMed PMID: 24391160.
3)

Nuttall GA, Brown MJ, Stombaugh JW, et al. Time and cardiac risk of surgery after bare-metal stent percutaneous coronary intervention. Anesthesiology. 2008; 109:588–595
4)

Rabbitts JA, Nuttall GA, Brown MJ, et al. Cardiac risk of noncardiac surgery after percutaneous coronary intervention with drug-eluting stents. Anesthesiology. 2008; 109:596–604
5) , 6)

Landesberg G, Beattie WS, Mosseri M, et al. Perioperative myocardial infarction. Circulation. 2009; 119:2936–2944
7)

Hilkens NA, Algra A, Kappelle LJ, Bath PM, Csiba L, Rothwell PM, Greving JP; CAT Collaboration. Early time course of major bleeding on antiplatelet therapy after TIA or ischemic stroke. Neurology. 2018 Jan 26. pii: 10.1212/WNL.0000000000004997. doi: 10.1212/WNL.0000000000004997. [Epub ahead of print] PubMed PMID: 29374102.
8)

Ravina K, Strickland BA, Buchanan IA, Rennert RC, Kim PE, Fredrickson VL, Russin JJ. Postoperative antiplatelet therapy in the treatment of complex basilar apex aneurysms implementing Hunterian ligation and extracranial-to-intracranial bypass: review of the literature with an illustrative case report. World Neurosurg. 2018 Dec 8. pii: S1878-8750(18)32798-0. doi: 10.1016/j.wneu.2018.11.237. [Epub ahead of print] Review. PubMed PMID: 30537547.

Update: Antiplatelet reversal

Antiplatelet reversal

Antiplatelet therapy is common and complicates the operative management of acute intracranial hemorrhage. Little data exist to guide antiplatelet reversal strategies.

The use of antithrombotic agents, including anticoagulants, antiplatelet agents, and thrombolytics has increased and is expected to continue to rise. Although antithrombotic-associated intracranial hemorrhage can be devastating, rapid reversal of coagulopathy may help limit hematoma expansion and improve outcomes.

Data assessing the relationship between outcome and prehospital antiplatelet agents in the setting of ICH is conflicting in both the trauma and the stroke literature. Only one retrospective review specifically addressed outcomes after attempted reversal with platelet transfusion. Further study is needed to determine whether platelet transfusion ameliorates hematoma enlargement and/or improves outcome in the setting of acute ICH 1).

Raimondi et al., recommend discontinuation of the antiplatelet, as well as administration of platelet transfusions and desmopressin only in the setting of life-threatening bleeding 2).


An online survey detailing antiplatelet reversal strategies in patients presenting with acute operative intracranial hemorrhage (subdural hematoma(SDH), epidural hematoma (EDH), and intracerebral hemorrhage (ICH) was distributed to board certified neurosurgeons in the North America.

Of the 2,782 functional email addresses, there were 493 (17.7%) responses to question #1 and 429 (15.4%) completed surveys. Most respondents chose to perform no additional laboratory testing prior to surgical intervention, regardless of hemorrhage type. The most common antiplatelet reversal strategy in the presence of aspirin was platelet transfusion (SDH and ICH) or no intervention (EDH). The most common antiplatelet reversal strategy in the presence of an Adenosine diphosphate receptor inhibitor or DAPT was platelet transfusion or platelet transfusion with DDAVP administration. There was a statistically significant difference in management strategy depending on the antiplatelet therapy (p < 0.001).

When patients on antiplatelet medication present with operative intracranial hemorrhage, the majority of neurosurgeons do not perform qualitative platelet function testing. Antiplatelet reversal strategies are significantly influenced by the antiplatelet therapy with more aggressive reversal strategies employed in the presence of ADP antagonist3).

References

1)

Campbell PG, Sen A, Yadla S, Jabbour P, Jallo J. Emergency reversal of antiplatelet agents in patients presenting with an intracranial hemorrhage: a clinical review. World Neurosurg. 2010 Aug-Sep;74(2-3):279-85. doi: 10.1016/j.wneu.2010.05.030. Review. PubMed PMID: 21492561.
2)

Raimondi P, Hylek EM, Aronis KN. Reversal Agents for Oral Antiplatelet and Anticoagulant Treatment During Bleeding Events: Current Strategies. Curr Pharm Des. 2017;23(9):1406-1423. doi: 10.2174/1381612822666161205110843. Review. PubMed PMID: 27917717.
3)

Foreman PM, Ilyas A, Mooney J, Schmalz PGR, Walters BC, Griessenauer CJ. Antiplatelet Medication Reversal Strategies in Operative Intracranial Hemorrhage: A Survey of Practicing Neurosurgeons. World Neurosurg. 2018 May 18. pii: S1878-8750(18)31017-9. doi: 10.1016/j.wneu.2018.05.064. [Epub ahead of print] PubMed PMID: 29783009.
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