Case Series about the Changed Antiplatelet Protocol for Carotid Endarterectomy in a Teaching Hospital: More Patients with Complications?

Abstract

Introduction In the Netherlands, clopidogrel monotherapy increasingly replaces acetylsalicylic acid and extended release dipyridamole as the first-choice antiplatelet therapy after ischemic stroke. It is unknown whether the risk of peri- and postoperative hemorrhage in carotid artery surgery is higher in patients using clopidogrel monotherapy compared with acetylsalicylic acid and extended release dipyridamole. We therefore retrospectively compared occurrence of perioperative major and (clinical relevant) minor bleedings during and after carotid endarterectomy of two groups using different types of platelet aggregation inhibition after changing our daily practice protocol in our center.

Material and Methods A consecutive series of the most recent 80 carotid endarterectomy patients (November 2015–August 2017) treated with the new regime (clopidogrel monotherapy) were compared with the last 80 (January 2012–November 2015) consecutive patients treated according to the old protocol (acetylsalicylic acid and dipyridamole). The primary endpoint was any major bleeding during surgery or in the first 24 to 72 hours postoperatively. Secondary outcomes within 30 days after surgery included minor (re)bleeding postoperative stroke with persistent or transient neurological deficit, persisting or transient neuropraxia, asymptomatic restenosis or occlusion, (transient) headache. Reporting of this study is in line with the ‘Strengthening the Reporting of Observational Studies in Epidemiology’ statement.

Results Although statistical differences were observed, from a clinical perspective both patients groups were comparable. Postoperative hemorrhage requiring reexploration for hemostasis occurred in none of the 80 patients in the group of the clopidogrel monotherapy (new protocol) and it occurred in one of the 80 patients (1%) who was using acetylsalicylic acid and dipyridamole (old protocol). In three patients (4%) in the clopidogrel monotherapy and one patient (1%) in the acetylsalicylic acid and extended release dipyridamole protocol an ipsilateral stroke was diagnosed.

Conclusion In this retrospective consecutive series the incidence of postoperative ischemic complications and perioperative hemorrhage after carotid endarterectomy (CEA) seemed to be comparable in patients using clopidogrel monotherapy versus acetylsalicylic acid and extended release dipyridamole for secondary prevention after a cerebrovascular event. This study fuels the hypothesis that short- and midterm complications of clopidogrel and the combination acetylsalicylic acid and extended release dipyridamole are comparable.

Keywords

acetylsalicylic acid - ASA - bleeding - carotid endarterectomy - carotid artery - clopidogrel - dipyridamole - complication

Presentation

This study was presented at the annual meeting of the Dutch Society of Vascular Surgery (NVvV) on November 2^nd 2018.

• References

• 1 Kwok CS, Shoamanesh A, Copley HC, Myint PK, Loke YK, Benavente OR. Efficacy of antiplatelet therapy in secondary prevention following lacunar stroke: pooled analysis of randomized trials. Stroke 2015; 46 (04) 1014-1023
• 2 Furie KL, Kasner SE, Adams RJ. , et al; American Heart Association Stroke Council, Council on Cardiovascular Nursing, Council on Clinical Cardiology, and Interdisciplinary Council on Quality of Care and Outcomes Research. Guidelines for the prevention of stroke in patients with stroke or transient ischemic attack: a guideline for healthcare professionals from the american heart association/american stroke association. Stroke 2011; 42 (01) 227-276
• 3 Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. ; ESPRIT Study Group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet 2006; 367 (9523): 1665-1673
• 4 Keus F, Wetterslev J, Gluud C, van Laarhoven CJ. Evidence at a glance: error matrix approach for overviewing available evidence. BMC Med Res Methodol 2010; 10: 90
• 5 Diener HC, Sacco RL, Yusuf S. , et al; Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) study group. Effects of aspirin plus extended-release dipyridamole versus clopidogrel and telmisartan on disability and cognitive function after recurrent stroke in patients with ischaemic stroke in the Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS) trial: a double-blind, active and placebo-controlled study. Lancet Neurol 2008; 7 (10) 875-884
• 6 Brown MT, Bussell JK. Medication adherence: WHO cares?. Mayo Clin Proc 2011; 86 (04) 304-314
• 7 Stone DH, Goodney PP, Schanzer A. , et al; Vascular Study Group of New England. Clopidogrel is not associated with major bleeding complications during peripheral arterial surgery. J Vasc Surg 2011; 54 (03) 779-784
• 8 Baracchini C, Gruppo M, Mazzalai F, Lorenzetti R, Meneghetti G, Ballotta E. Predictors of neck bleeding after eversion carotid endarterectomy. J Vasc Surg 2011; 54 (03) 699-705
• 9 Wait SD, Abla AA, Killory BD, Starke RM, Spetzler RF, Nakaji P. Safety of carotid endarterectomy while on clopidogrel (Plavix). Clinical article. J Neurosurg 2010; 113 (04) 908-912
• 10 Morales Gisbert SM, Sala Almonacil VA, Zaragozá García JM, Genovés Gascó B, Gómez Palonés FJ, Ortiz Monzón E. Predictors of cervical bleeding after carotid endarterectomy. Ann Vasc Surg 2014; 28 (02) 366-374
• 11 Rothwell PM, Eliasziw M, Gutnikov SA, Warlow CP, Barnett HJ. ; Carotid Endarterectomy Trialists Collaboration. Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery. Lancet 2004; 363 (9413): 915-924
• 12 Neurologie NVvN. Diagnostiek, behandeling en zorg voor patiënten met een beroerte. 2008 Guideline. Available from: https://internisten.nl/sites/internisten.nl/files/uploads/6N/EE/6NEEZDkyKDcbjVkcazdTMQ/richtlijn_2008_Beroerte.pdf. Accessed October 24, 2017
• 13 Rerkasem K, Rothwell PM. Local versus general anaesthesia for carotid endarterectomy. Cochrane Database Syst Rev 2008; (04) CD000126
• 14 Demirel S, Macek L, Bruijnen H, Hakimi M, Böckler D, Attigah N. Eversion carotid endarterectomy is associated with decreased baroreceptor sensitivity compared to the conventional technique. Eur J Vasc Endovasc Surg 2012; 44 (01) 1-8
• 15 Koning GG, Lüning TH, ter Bruggen JP. Een vrouw met linkszijdig retrobulbaire pijn, fotofobie en hornersyndroom. Nederlands Tijdschrift voor Geneeskunde (Stud. ed.). 2007. ;10(3):55–57
• 16 Karimi A, van der Vliet JA, Wetterslev J. , et al. Protocol: primary closure versus patch angioplasty in carotid endarterectomy: a systematic review with meta-analyses and trial sequential analyses of randomized clinical trials 2014. Available from: http://www.crd.york.ac.uk/PROSPEROFILES/13416_PROTOCOL_20140726.pdf . Accessed October 16, 2018
• 17 Markus HS, Droste DW, Kaps M. , et al. Dual antiplatelet therapy with clopidogrel and aspirin in symptomatic carotid stenosis evaluated using doppler embolic signal detection: the Clopidogrel and Aspirin for Reduction of Emboli in Symptomatic Carotid Stenosis (CARESS) trial. Circulation 2005; 111 (17) 2233-2240
• 18 Doig D, Turner EL, Dobson J. , et al; ICSS Investigators. Risk factors for stroke, myocardial infarction, or death following carotid endarterectomy: results from the international carotid stenting study. Eur J Vasc Endovasc Surg 2015; 50 (06) 688-694
• 19 Guyatt GH, Oxman AD, Kunz R. , et al. GRADE guidelines 6. Rating the quality of evidence--imprecision. J Clin Epidemiol 2011; 64 (12) 1283-1293
• 20 von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP. ; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol 2008; 61 (04) 344-349
• 21 Guyatt GH, Oxman AD, Kunz R, Vist GE, Falck-Ytter Y, Schünemann HJ. ; GRADE Working Group. What is “quality of evidence” and why is it important to clinicians?. BMJ 2008; 336 (7651): 995-998
• 22 Davis KA, Miyares MA, Dietrich E. Dual antiplatelet therapy with clopidogrel and aspirin after ischemic stroke: a review of the evidence. Am J Health Syst Pharm 2015; 72 (19) 1623-1629
• 23 Brandler ES, Sharma M. Early dual antiplatelet therapy in stroke: should we take the CHANCE?. Ann Transl Med 2015; 3 (13) 177
• 24 Tan S, Xiao X, Ma H. , et al. Clopidogrel and aspirin versus aspirin alone for stroke prevention: a meta-analysis. PLoS One 2015; 10 (08) e0135372
• 25 Weinrich M, Schindler P, Kundt G, Klar E, Bünger CM. Influence of local hemostatic and antiplatelet agents on the incidence of bleeding complications in carotid endarterectomies. Clin Hemorheol Microcirc 2014; 58 (01) 271-279
• 26 Hale B, Pan W, Misselbeck TS, Lee VV, Livesay JJ. Combined clopidogrel and aspirin therapy in patients undergoing carotid endarterectomy is associated with an increased risk of postoperative bleeding. Vascular 2013; 21 (04) 197-204
• 27 Oldag A, Schreiber S, Schreiber S. , et al. Risk of wound hematoma at carotid endarterectomy under dual antiplatelet therapy. Langenbecks Arch Surg 2012; 397 (08) 1275-1282
• 28 de Borst GJ, Hilgevoord AA, de Vries JP. , et al. Influence of antiplatelet therapy on cerebral micro-emboli after carotid endarterectomy using postoperative transcranial Doppler monitoring. Eur J Vasc Endovasc Surg 2007; 34 (02) 135-142
• 29 Medicijnkosten.nl. [Internet]. www.medicijnkosten.nl . Zorginstituut Nederland; 2017 . Available from: https://www.medicijnkosten.nl/databank?medicijnId=1697&hoeveelheid=1&niveau=2 . Accessed November 24, 2017
• 30 Illuminati G, Schneider F, Pizzardi G, Masci F, Calio' FG, Ricco JB. Dual antiplatelet therapy does not increase the risk of bleeding after carotid endarterectomy: results of a prospective study. Ann Vasc Surg 2017; 40: 39-43