Journal of Korean Neurosurgical Society

The Korean Neurosurgical Society (대한신경외과학회)
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The Efficacy of P2Y12 Reactive Unit to Predict the Periprocedural Thromboembolic and Hemorrhagic Complications According to Clopidogrel Responsiveness and Safety of Modification of Dual Antiplatelet Therapy : A Meta-Analysis

  • Kim, Hyun Jung (Department of Public Health, Graduate School of Korea University) ;
  • Oh, Jae Sang (Department of Neurosurgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine) ;
  • Park, Sukh Que (Department of Neurosurgery, Soonchunhyang University Seoul, Hospital, Soonchunhyang University College of Medicine) ;
  • Yoon, Seok Mann (Department of Neurosurgery, Soonchunhyang University Cheonan Hospital, Soonchunhyang University College of Medicine) ;
  • Ahn, Hyeong Sik (Department of Public Health, Graduate School of Korea University) ;
  • Kim, Bum Tae (Department of Neurosurgery, Soonchunhyang University Bucheon Hospital, Soonchunhyang University College of Medicine)
  • Received : 2019.03.27
  • Accepted : 2019.08.07
  • Published : 2020.09.01
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Abstract

The efficacy of P2Y12 reaction unit (PRU) of VerifyNow still remains as a controversial issue in neurointervention. So we investigated the usefulness of PRU of VerifyNow to predict the peri-procedural thromboembolic events (TE) and hemorrhagic events (HE). And we evaluated the safety of modified dual antiplatelet therapy (DAPT) or triple antiplatelet therapy (TAPT) for clopidogrel hyporesponders. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and Scopus on August 19 2018. Data was collected the 1) incidence of TE between clopidogrel responder and clopidogrel hypo-responder, 2) incidence of HE between clopidogrel hyper-responder and clopidogrel responder and hypo-responder, and 3) incidence of TE and HE between modified DAPT or TAPT and standard DAPT in clopidogrel hypo-responder. High cut-off value of PRU was defined as PRU >40% or <220. Fifteen studies were enrolled. Clopidogrel responder showed lower incidence of TE than hypo-responder (risk ratio [RR], 0.32; 95% confidence interval [CI], 0.17-0.61; p<0.001). With the high cut-off value of PRU, clopidogrel responder showed more lower incidence of TE than hypo-responder (RR, 0.11; 95% CI, 0.02-0.45; p=0.002). The incidence of periprocedural HE have higher on clopidogrel hyper-responder than clopidogrel responder and hypo-responder (RR, 4.26; 95% CI, 1.10-16.44; p=0.04; I2=66%). The incidence of periprocedural TE after changing regimen of DAPT for clopidogrel hypo-responder have a tendency to reduce, but there was no significant difference between modified DAPT or TAPT group and standard DAPT group (p>0.05). The incidence of periprocedural HE after changing regimen of DAPT for clopidogrel hypo-responder was no significant difference between modified DAPT or TAPT group and standard DAPT group (p>0.05). PRU is a useful tool as a predictor of peri-procedural TE or HE on neurointervention. PRU has a threshold effect of cut-off value to predict the peri-procedural TE. Modified DAPT or TAPT to prevent TE in clopidogrel hypo-responders could not reduce the incidence of TE. We should investigate the further research about modification of regiment on neurointervention.

Keywords

References

  1. Angiolillo DJ, Shoemaker SB, Desai B, Yuan H, Charlton RK, Bernardo E, et al. : Randomized comparison of a high clopidogrel maintenance dose in patients with diabetes mellitus and coronary artery disease: results of the optimizing antiplatelet therapy in diabetes mellitus (OPTIMUS) study. Circulation 115 : 708-716, 2007 https://doi.org/10.1161/CIRCULATIONAHA.106.667741
  2. Asai T, Miyachi S, Izumi T, Matsubara N, Haraguchi K, Yamanouchi T, et al. : Relationship between low response to clopidogrel and periprocedural ischemic events with coil embolization for intracranial aneurysms. J Neurointerv Surg 8 : 752-755, 2016 https://doi.org/10.1136/neurintsurg-2015-011727
  3. Bender MT, Lin LM, Colby GP, Lubelski D, Huang J, Tamargo RJ, et al. : P2Y12 hyporesponse (PRU>200) is not associated with increased thromboembolic complications in anterior circulation Pipeline. J Neurointerv Surg 9 : 978-981, 2017 https://doi.org/10.1136/neurintsurg-2016-012618
  4. Berger JS, Bhatt DL, Steinhubl SR, Shao M, Steg PG, Montalescot G, et al. : Smoking, clopidogrel, and mortality in patients with established cardiovascular disease. Circulation 120 : 2337-2344, 2009 https://doi.org/10.1161/CIRCULATIONAHA.109.866533
  5. Biondi-Zoccai G, Lotrionte M, Agostoni P, Abbate A, Romagnoli E, Sangiorgi G, et al. : Adjusted indirect comparison meta-analysis of prasugrel versus ticagrelor for patients with acute coronary syndromes. Int J Cardiol 150 : 325-331, 2011 https://doi.org/10.1016/j.ijcard.2010.08.035
  6. Collet JP, Cuisset T, Range G, Cayla G, Elhadad S, Pouillot C, et al. : Bedside monitoring to adjust antiplatelet therapy for coronary stenting. N Engl J Med 367 : 2100-2109, 2012 https://doi.org/10.1056/NEJMoa1209979
  7. Daou B, Starke RM, Chalouhi N, Barros G, Tjoumakaris S, Rosenwasser RH, et al. : P2Y12 reaction units: effect on hemorrhagic and thromboembolic complications in patients with cerebral aneurysms treated with the pipeline embolization device. Neurosurgery 78 : 27-33, 2016 https://doi.org/10.1227/NEU.0000000000000978
  8. Delgado Almandoz JE, Crandall BM, Scholz JM, Fease JL, Anderson RE, Kadkhodayan Y, et al. : Pre-procedure P2Y12 reaction units value predicts perioperative thromboembolic and hemorrhagic complications in patients with cerebral aneurysms treated with the pipeline embolization device. J Neurointerv Surg 5 : iii3-iii10, 2013 https://doi.org/10.1136/neurintsurg-2012-010582
  9. Desai NR, Mega JL, Jiang S, Cannon CP, Sabatine MS : Interaction between cigarette smoking and clinical benefit of clopidogrel. J Am Coll Cardiol 53 : 1273-1278, 2009 https://doi.org/10.1016/j.jacc.2008.12.044
  10. Drazin D, Choulakian A, Nuno M, Kornbluth P, Alexander MJ : Body weight: a risk factor for subtherapeutic antithrombotic therapy in neurovascular stenting. J Neurointerv Surg 3 : 177-181, 2011 https://doi.org/10.1136/jnis.2010.004085
  11. Ferroni P, Basili S, Falco A, Davi G : Platelet activation in type 2 diabetes mellitus. J Thromb Haemost 2 : 1282-1291, 2004 https://doi.org/10.1111/j.1538-7836.2004.00836.x
  12. Fifi JT, Brockington C, Narang J, Leesch W, Ewing SL, Bennet H, et al. : Clopidogrel resistance is associated with thromboembolic complications in patients undergoing neurovascular stenting. AJNR Am J Neuroradiol 34 : 716-720, 2013 https://doi.org/10.3174/ajnr.A3405
  13. Gonzalez A, Moniche F, Cayuela A, Garcia-Lozano JR, Torrecillas F, Escudero-Martinez I, et al. : Effect of CYP2C19 polymorphisms on the platelet response to clopidogrel and influence on the effect of high versus standard dose clopidogrel in carotid artery stenting. Eur J Vasc Endovasc Surg 51 : 175-186, 2016 https://doi.org/10.1016/j.ejvs.2015.09.020
  14. Gurbel PA, Bliden KP, Butler K, Tantry US, Gesheff T, Wei C, et al. : Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation 120 : 2577-2585, 2009 https://doi.org/10.1161/CIRCULATIONAHA.109.912550
  15. Ha EJ, Cho WS, Kim JE, Cho YD, Choi HH, Kim T, et al. : Prophylactic antiplatelet medication in endovascular treatment of intracranial aneurysms: low-dose prasugrel versus clopidogrel. AJNR Am J Neuroradiol 37 : 2060-2065, 2016 https://doi.org/10.3174/ajnr.A4864
  16. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. : The cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ 343 : d5928, 2011 https://doi.org/10.1136/bmj.d5928
  17. Hochholzer W, Ruff CT, Mesa RA, Mattimore JF, Cyr JF, Lei L, et al. : Variability of individual platelet reactivity over time in patients treated with clopidogrel: insights from the ELEVATE-TIMI 56 trial. J Am Coll Cardiol 64 : 361-368, 2014 https://doi.org/10.1016/j.jacc.2014.03.051
  18. Hokimoto S, Mizobe M, Akasaka T, Arima Y, Kaikita K, Nakagawa K, et al. : Impact of CYP2C19 polymorphism and proton pump inhibitors on platelet reactivity to clopidogrel and clinical outcomes following stent implantation. Thromb Res 133 : 599-605, 2014 https://doi.org/10.1016/j.thromres.2014.01.003
  19. Hwang G, Huh W, Lee JS, Villavicencio JB, Villamor RB Jr, Ahn SY, et al. : Standard vs modified antiplatelet preparation for preventing thromboembolic events in patients with high on-treatment platelet reactivity undergoing coil embolization for an unruptured intracranial aneurysm: a randomized clinical trial. JAMA Neurol 72 : 764-772, 2015 https://doi.org/10.1001/jamaneurol.2015.0654
  20. Kang HS, Kwon BJ, Kim JE, Han MH : Preinterventional clopidogrel response variability for coil embolization of intracranial aneurysms: clinical implications. AJNR Am J Neuroradiol 31 : 1206-1210, 2010 https://doi.org/10.3174/ajnr.A2051
  21. Kashiwazaki D, Kuwayama N, Akioka N, Hayakawa Y, Kuroda S : The roles and issues of P2Y12 percent inhibition assessed by VerifyNow assay for patients undergoing neurointervention: a prospective study. J Stroke Cerebrovasc Dis 23 : 1830-1836, 2014 https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.04.014
  22. Kim BJ, Kwon JY, Jung JM, Lee DH, Kang DW, Kim JS, et al. : Association between silent embolic cerebral infarction and continuous increase of P2Y12 reaction units after neurovascular stenting. J Neurosurg 121 : 891-898, 2014 https://doi.org/10.3171/2014.6.JNS132448
  23. Kim CH, Hwang G, Kwon OK, Ban SP, Chinh ND, Tjahjadi M, et al. : P2Y12 reaction units threshold for implementing modified antiplatelet preparation in coil embolization of unruptured aneurysms: a prospective validation study. Radiology 282 : 542-551, 2017 https://doi.org/10.1148/radiol.2016160542
  24. Kim MS, Park ES, Park JB, Lyo IU, Sim HB, Kwon SC : Clopidogrel response variability in unruptured intracranial aneurysm patients treated with stent-assisted endovascular coil embolization : is follow-up clopidogrel response test necessary? J Korean Neurosurg Soc 61 : 201-211, 2018 https://doi.org/10.3340/jkns.2017.0303.009
  25. Lee DH, Arat A, Morsi H, Shaltoni H, Harris JR, Mawad ME : Dual antiplatelet therapy monitoring for neurointerventional procedures using a point-of-care platelet function test: a single-center experience. AJNR Am J Neuroradiol 29 : 1389-1394, 2008 https://doi.org/10.3174/ajnr.A1070
  26. Mega JL, Hochholzer W, Frelinger AL 3rd, Kluk MJ, Angiolillo DJ, Kereiakes DJ, et al. : Dosing clopidogrel based on CYP2C19 genotype and the effect on platelet reactivity in patients with stable cardiovascular disease. JAMA 306 : 2221-2228, 2011
  27. Mehran R, Rao SV, Bhatt DL, Gibson CM, Caixeta A, Eikelboom J, et al. : Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 123 : 2736-2747, 2011 https://doi.org/10.1161/CIRCULATIONAHA.110.009449
  28. Nishi H, Nakahara I, Matsumoto S, Hashimoto T, Ohta T, Sadamasa N, et al. : Platelet reactivity and hemorrhage risk in neurointerventional procedures under dual antiplatelet therapy. J Neurointerv Surg 8 : 949-953, 2016 https://doi.org/10.1136/neurintsurg-2015-011844
  29. Nordeen JD, Patel AV, Darracott RM, Johns GS, Taussky P, Tawk RG, et al. : Clopidogrel resistance by P2Y12 platelet function testing in patients undergoing neuroendovascular procedures: incidence of ischemic and hemorrhagic complications. J Vasc Interv Neurol 6 : 26-34, 2013
  30. Pierot L, Wakhloo AK : Endovascular treatment of intracranial aneurysms: current status. Stroke 44 : 2046-2054, 2013 https://doi.org/10.1161/STROKEAHA.113.000733
  31. Prabhakaran S, Wells KR, Lee VH, Flaherty CA, Lopes DK : Prevalence and risk factors for aspirin and clopidogrel resistance in cerebrovascular stenting. AJNR Am J Neuroradiol 29 : 281-285, 2008 https://doi.org/10.3174/ajnr.A0818
  32. Price MJ, Berger PB, Teirstein PS, Tanguay JF, Angiolillo DJ, Spriggs D, et al. : Standard- vs high-dose clopidogrel based on platelet function testing after percutaneous coronary intervention: The GRAVITAS randomized trial. JAMA 305 : 1097-1105, 2011 https://doi.org/10.1001/jama.2011.290
  33. Rosano GMC, Seferovic P : 2017 ESC guidelines focus on dual antiplatelet therapy. Eur Heart J Cardiovasc Pharmacother 4 : 131-132, 2018 https://doi.org/10.1093/ehjcvp/pvy007
  34. Ryu DS, Hong CK, Sim YS, Kim CH, Jung JY, Joo JY : Anti-platelet drug resistance in the prediction of thromboembolic complications after neurointervention. J Korean Neurosurg Soc 48 : 319-324, 2010 https://doi.org/10.3340/jkns.2010.48.4.319
  35. Song J, Shin YS : Antiplatelet drug resistance did not increase the thromboembolic events after stent-assisted coiling of unruptured intracranial aneurysm: a single center experience of 99 cases. Neurol Sci 38 : 879-885, 2017 https://doi.org/10.1007/s10072-017-2859-z
  36. Tan LA, Keigher KM, Munich SA, Moftakhar R, Lopes DK : Thromboembolic complications with pipeline embolization device placement: impact of procedure time, number of stents and pre-procedure P2Y12 reaction unit (PRU) value. J Neurointerv Surg 7 : 217-221, 2015 https://doi.org/10.1136/neurintsurg-2014-011111
  37. Ueno M, Ferreiro JL, Desai B, Tomasello SD, Tello-Montoliu A, Capodanno D, et al. : Cigarette smoking is associated with a dose-response effect in clopidogrel-treated patients with diabetes mellitus and coronary artery disease: results of a pharmacodynamic study. JACC Cardiovasc Interv 5 : 293-300, 2012
  38. Wong P, Tesoro E, Aletich V, Alaraj A : Accumetrics-based clopidogrel dosing in endovascular neurosurgery. Neurol Res 37 : 998-1005, 2015 https://doi.org/10.1179/1743132815Y.0000000084

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