[en] [en] BACKROUND AND PURPOSE: Role of peri-procedural heparin as an adjuvant treatment during mechanical thrombectomy (MT) for patients contra-indicated for alteplase remains a source of debate.
METHODS: We included patients from the multicenter French register ETIS that underwent MT without administration of alteplase, and compared patients who received heparin during MT with patients who did not. Heparin impact on outcome were analyzed regarding final TICI score, NIHSS at day one, modified rankin scale (mRS) and intracranial hemorrhagic transformation on imaging at day one.
RESULTS: Over 1031 patients, 751 were included between January 2015 and June 2018 in 6 different centers, and 223 (26.69%) received heparin. Heparin administration was associated with a significant deleterious effect on NIHSS at 24h [adjusted OR = 1.2; p = 0.02], mRS at 3 months [adjusted OR 1.58; p = 0.03], and on complete reperfusion [TICI 3 adjusted OR 0.68; p = 0.02]. Heparin administration was associated with a significant reduction of hemorrhagic transformation [adjusted OR 0.48; p = 0.00005].
CONCLUSIONS: Heparin administration during MT seems deleterious for reperfusion and functional outcome. Randomized trials are needed to identify the role of antithrombotic treatments, such as heparin, in the setting of acute ischemic stroke management.
Disciplines :
Neurology
Author, co-author :
Hebert, Solène; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France. Electronic address: shebert@for.paris
Clavel, Pierre; Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France
Maier, Benjamin; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France
Mizutani, Katsuhiro ; Neurovascular Unit, Foch Hospital, Suresnes, France
Delvoye, François ; Université de Liège - ULiège > Département des sciences cliniques ; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France
Lapergue, Bertrand; Neurovascular Unit, Foch Hospital, Suresnes, France
Maacha, Malek Ben; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France
Fahed, Robert; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France, Laboratory of Vascular Translational Science, U1148 Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France, Université Paris Denis Diderot, Sorbonne Paris Cite, France
Escalard, Simon ; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France
Desilles, Jean-Philippe; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France, Laboratory of Vascular Translational Science, U1148 Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France, Université Paris Denis Diderot, Sorbonne Paris Cite, France
Redjem, Hocine; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France
Ciccio, Gabriele; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France
Smajda, Stanislas; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France
Blanc, Raphael; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France, Laboratory of Vascular Translational Science, U1148 Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France, Université Paris Denis Diderot, Sorbonne Paris Cite, France
Piotin, Michel; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France, Laboratory of Vascular Translational Science, U1148 Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France, Université Paris Denis Diderot, Sorbonne Paris Cite, France
Mazighi, Mikael; Interventional Neuroradiology Unit, Fondation Rothschild Hospital, Paris, France, Laboratory of Vascular Translational Science, U1148 Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France, Université Paris Denis Diderot, Sorbonne Paris Cite, France
Powers, WJ, Derdeyn, CP, Biller, J, Coffey, CS, Hoh, BL, Jauch, EC, et al. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 46 (2015), 3020–3035.
Goyal, M, Menon, BK, van Zwam, WH, Dippel, DWJ, Mitchell, PJ, Demchuk, AM, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. The Lancet 387 (2016), 1723–1731.
Schönenberger, S, Möhlenbruch, M, Pfaff, J, Mundiyanapurath, S, Kieser, M, Bendszus, M, et al. Sedation vs. Intubation for Endovascular Stroke TreAtment (SIESTA)-a randomized monocentric trial. Int J Stroke 10 (2015), 969–978.
Simonsen, CZ, Yoo, AJ, Sørensen, LH, Juul, N, Johnsen, SP, Andersen, G, et al. Effect of general anesthesia and conscious sedation during endovascular therapy on infarct growth and clinical outcomes in acute ischemic stroke: a randomized clinical trial. JAMA Neurology, 75, 2018, 470.
Maïer, B, Gory, B, Taylor, G, Labreuche, J, Blanc, R, Obadia, M, et al. Mortality and disability according to baseline blood pressure in acute ischemic stroke patients treated by Thrombectomy: a collaborative pooled analysis. J Am Heart Assoc, 2017, 6 [Internet].[cited 2019 Apr 23] Available from: https://www.ahajournals.org/doi/10.1161/JAHA.117.006484.
Lapergue, B, Blanc, R, Gory, B, Labreuche, J, Duhamel, A, Marnat, G, et al. Effect of endovascular contact aspiration vs stent retriever on revascularization in patients with acute ischemic stroke and large vessel occlusion: the aster randomized clinical trial. JAMA, 318, 2017, 443.
Turk, AS, Siddiqui, A, Fifi, JT, De Leacy, RA, Fiorella, DJ, Gu, E, et al. Aspiration thrombectomy versus stent retriever thrombectomy as first-line approach for large vessel occlusion (COMPASS): a multicentre, randomised, open label, blinded outcome, non-inferiority trial. Lancet 393 (2019), 998–1008.
van de Graaf, RA, Chalos, V, Del Zoppo, GJ, van der Lugt, A, Dippel, DWJ, Roozenbeek, B, Periprocedural antithrombotic treatment during acute mechanical thrombectomy for ischemic stroke: a systematic review. Front Neurol, 9, 2018, 238.
Dargazanli, C, Consoli, A, Barral, M, Labreuche, J, Redjem, H, Ciccio, G, et al. Impact of modified TICI 3 versus modified TICI 2b reperfusion score to predict good outcome following endovascular therapy. Am J Neuroradiol 38 (2017), 90–96.
Bendszus, M, Koltzenburg, M, Bartsch, AJ, Goldbrunner, R, Günthner-Lengsfeld, T, Weilbach, FX, et al. Heparin and air filters reduce embolic events caused by intra-arterial cerebral angiography: a prospective, randomized trial. Circulation 110 (2004), 2210–2215.
Boysen, G, Study Group, ECASS, European Cooperative Acute Stroke Study (ECASS): (rt-PA-Thrombolysis in acute stroke) study design and progress report. Eur. J. Neurol. 1 (1995), 213–219.
National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N. Engl. J. Med. 333 (1995), 1581–1587.
Desilles, J-P, Consoli, A, Redjem, H, Coskun, O, Ciccio, G, Smajda, S, et al. Successful reperfusion with mechanical thrombectomy is associated with reduced disability and mortality in patients with pretreatment diffusion-weighted imaging-alberta stroke program early computed tomography score ≤6. Stroke 48 (2017), 963–969.
Powers, WJ, Rabinstein, AA, Ackerson, T, Adeoye, OM, Bambakidis, NC, Becker, K, et al. 2018 Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke, 2018, 49 [Internet].[cited 2019 Dec 9]Available from: https://www.ahajournals.org/doi/10.1161/STR.0000000000000158.
del Zoppo, GJ, Higashida, RT, Furlan, AJ, Pessin, MS, Rowley, HA, Gent, M, PROACT: a phase II randomized trial of recombinant pro-urokinase by direct arterial delivery in acute middle cerebral artery stroke. Stroke 29 (1998), 4–11.
Nahab, F, Walker, GA, Dion, JE, Smith, WS, Safety of periprocedural heparin in acute ischemic stroke endovascular therapy: the multi MERCI trial. J Stroke Cerebrovasc Dis 21 (2012), 790–793.
Winningham, MJ, Haussen, DC, Nogueira, RG, Liebeskind, DS, Smith, WS, Lutsep, HL, et al. Periprocedural heparin use in acute ischemic stroke endovascular therapy: the TREVO 2 trial. J Neurointerv Surg 10 (2018), 611–614.
Farook, N, Haussen, D, Sur, S, Snelling, B, Gersey, Z, Yavagal, D, et al. Role of heparin during endovascular therapy for acute ischemic stroke. Clin Neurol Neurosurg 145 (2016), 64–67.
Wang, DT, Churilov, L, Dowling, R, Mitchell, P, Yan, B, Successful recanalization post endovascular therapy is associated with a decreased risk of intracranial haemorrhage: a retrospective study. BMC Neurol, 15, 2015, 185.
del Zoppo, GJ, Schmid-Schönbein, GW, Mori, E, Copeland, BR, Chang, CM, Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke 22 (1991), 1276–1283.
del Zoppo, GJ, Mabuchi, T, Cerebral Microvessel Responses to Focal Ischemia. J Cereb Blood Flow Metab 23 (2003), 879–894.
von Brühl, M-L, Stark, K, Steinhart, A, Chandraratne, S, Konrad, I, Lorenz, M, et al. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 209 (2012), 819–835.
Downstream Microvascular Thrombosis in Cortical Venules Is an Early Response to Proximal Cerebral Arterial Occlusion. - PubMed - NCBI [Internet]. [cited 2018 Jul 25];Available from: https://www.ncbi.nlm.nih.gov/pubmed/29496683.
Soares, BP, Tong, E, Hom, J, Cheng, S-C, Bredno, J, Boussel, L, et al. Reperfusion is a more accurate predictor of follow-up infarct volume than recanalization: a proof of concept using CT in acute ischemic stroke patients. Stroke, 2010, 41 [Internet].[cited 2019 Apr 23]Available from: https://www.ahajournals.org/doi/10.1161/STROKEAHA.109.568766.
Chalumeau, V, Blanc, R, Redjem, H, Ciccio, G, Smajda, S, Desilles, J-P, et al. Anterior cerebral artery embolism during thrombectomy increases disability and mortality. J NeuroInterventional Surg 10 (2018), 1057–1062.
Yang, M, Huo, X, Gao, F, Wang, A, Ma, N, Liebeskind, DS, et al. Safety and efficacy of heparinization during mechanical Thrombectomy in acute ischemic stroke. Front Neurol, 2019, 10 [Internet].[cited 2019 Apr 23]Available from: https://www.frontiersin.org/article/10.3389/fneur.2019.00299/full.
van de Graaf, RA, Chalos, V, van Es, ACGM, Emmer, BJ, Lycklama à Nijeholt, GJ, van der Worp, HB, et al. Periprocedural intravenous heparin during endovascular treatment for ischemic stroke: results from the MR CLEAN registry. Stroke 50 (2019), 2147–2155.
Clinical Trials Register [Internet]. [cited 2019 Dec 2];Available from: https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-001466-21/NL.
