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Erschienen in: Journal of Neurology 8/2016

03.06.2016 | Original Communication

Antiplatelet drug resistance is associated with early neurological deterioration in acute minor ischemic stroke in the Chinese population

verfasst von: Xingyang Yi, Chun Wang, Ping Liu, Cheng Fu, Jing Lin, Yiming Chen

Erschienen in: Journal of Neurology | Ausgabe 8/2016

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Abstract

To evaluate the prevalence and risk factors of antiplatelet drug resistance and its association with early neurological deterioration (END) and recurrent ischemic stroke (RIS) in patients with acute minor stroke. Antiplatelet drug resistance was assessed by platelet aggregation assay in 426 patients with minor stroke who were receiving combined treatment of aspirin and clopidogrel. All patients were followed up for 90 days. The primary endpoint of the study was END within 10 days after admission. The secondary endpoints included RIS, myocardial infarction and death during 90 days of treatment. The safety endpoints were intracerebral or extracranial hemorrhagic events. Cox proportional hazard regression analysis was performed to determine the risk factors for the primary endpoint and secondary endpoints. Among the 426 patients, 24.4 % exhibited aspirin resistance, 35.9 % exhibited clopidogrel resistance, and 19.2 % displayed concomitant aspirin and clopidogrel resistance. In multivariate analysis, diabetes mellitus and high level of low density lipoprotein-cholesterol were independent risk factors for aspirin resistance, while diabetes mellitus was the only independent risk factor for clopidogrel resistance. END was observed in 93 (21.8 %) patients. Diabetes mellitus, high fasting blood glucose level, and concomitant aspirin and clopidogrel resistance were independent risk factors for END. RIS was observed in 40 (9.4 %) patients. Diabetes mellitus, hypertension, and concomitant aspirin and clopidogrel resistance were independent risk factors for RIS. Antiplatelet drug resistance is common in acute minor ischemic stroke patients and is associated with END and RIS after acute minor ischemic stroke in the Chinese population.
Clinical Trial Registration Information: http://​www.​chictr.​org/​. Unique Identifier: ChiCTR-OCH-14004724.
Literatur
3.
Zurück zum Zitat Smith EE, Fonarow GC, Reeves MJ, Cox M, Olson DM, Hernandez AF et al (2011) Outcomes in mild or rapidly improving stroke not treated with intravenous recombinant tissue-type plasminogen activator: findings from Get With The Guidelines-Stroke. Stroke 42:3110–3115. doi:10.1161/STROKEAHA.111.613208 CrossRefPubMed Smith EE, Fonarow GC, Reeves MJ, Cox M, Olson DM, Hernandez AF et al (2011) Outcomes in mild or rapidly improving stroke not treated with intravenous recombinant tissue-type plasminogen activator: findings from Get With The Guidelines-Stroke. Stroke 42:3110–3115. doi:10.​1161/​STROKEAHA.​111.​613208 CrossRefPubMed
7.
Zurück zum Zitat Lovett JK, Coull AJ, Rothwell PM (2004) Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies. Neurology 62:569–573CrossRefPubMed Lovett JK, Coull AJ, Rothwell PM (2004) Early risk of recurrence by subtype of ischemic stroke in population-based incidence studies. Neurology 62:569–573CrossRefPubMed
8.
Zurück zum Zitat Ois A, Gomis M, Rodriguez-Campello A, Cuadrado-Godia E, Jimenez-Conde J, Pont-Sunyer C et al (2008) Factors associated with a high risk of recurrence in patients with transient ischemic attack or minor stroke. Stroke 39:1717–1721. doi:10.1161/STROKEAHA.107.505438 CrossRefPubMed Ois A, Gomis M, Rodriguez-Campello A, Cuadrado-Godia E, Jimenez-Conde J, Pont-Sunyer C et al (2008) Factors associated with a high risk of recurrence in patients with transient ischemic attack or minor stroke. Stroke 39:1717–1721. doi:10.​1161/​STROKEAHA.​107.​505438 CrossRefPubMed
11.
Zurück zum Zitat Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD et al (2014) Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45:2160–2236. doi:10.1161/STR.0000000000000024 CrossRefPubMed Kernan WN, Ovbiagele B, Black HR, Bravata DM, Chimowitz MI, Ezekowitz MD et al (2014) Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 45:2160–2236. doi:10.​1161/​STR.​0000000000000024​ CrossRefPubMed
12.
Zurück zum Zitat CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group (1997) Lancet 349:1641–1649 CAST: randomised placebo-controlled trial of early aspirin use in 20,000 patients with acute ischaemic stroke. CAST (Chinese Acute Stroke Trial) Collaborative Group (1997) Lancet 349:1641–1649
13.
Zurück zum Zitat The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group (1997) Lancet 349:1569–1581 The International Stroke Trial (IST): a randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group (1997) Lancet 349:1569–1581
15.
Zurück zum Zitat Chen ZM, Sandercock P, Pan HC, Counsell C, Collins R, Liu LS et al (2000) Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups. Stroke 31:1240–1249CrossRefPubMed Chen ZM, Sandercock P, Pan HC, Counsell C, Collins R, Liu LS et al (2000) Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups. Stroke 31:1240–1249CrossRefPubMed
16.
Zurück zum Zitat Committee CS (1996) A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 348:1329–1339CrossRef Committee CS (1996) A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet 348:1329–1339CrossRef
17.
Zurück zum Zitat Makkar RR, Eigler NL, Kaul S, Frimerman A, Nakamura M, Shah PK et al (1998) Effects of clopidogrel, aspirin and combined therapy in a porcine ex vivo model of high-shear induced stent thrombosis. Eur Heart J 19:1538–1546CrossRefPubMed Makkar RR, Eigler NL, Kaul S, Frimerman A, Nakamura M, Shah PK et al (1998) Effects of clopidogrel, aspirin and combined therapy in a porcine ex vivo model of high-shear induced stent thrombosis. Eur Heart J 19:1538–1546CrossRefPubMed
21.
Zurück zum Zitat Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R et al (2010) Working group on high on-treatment platelet reactivity. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 56:919–933. doi:10.1016/j.jacc.2010.04.047 CrossRefPubMed Bonello L, Tantry US, Marcucci R, Blindt R, Angiolillo DJ, Becker R et al (2010) Working group on high on-treatment platelet reactivity. Consensus and future directions on the definition of high on-treatment platelet reactivity to adenosine diphosphate. J Am Coll Cardiol 56:919–933. doi:10.​1016/​j.​jacc.​2010.​04.​047 CrossRefPubMed
24.
Zurück zum Zitat Schwammenthal Y, Tsabari R, Shenkman B, Schwartz R, Matetzky S, Lubetsky A et al (2008) Aspirin responsiveness in acute brain ischaemia: association with stroke severity and clinical outcome. Cerebrovasc Dis 25:355–361. doi:10.1159/000118382 CrossRefPubMed Schwammenthal Y, Tsabari R, Shenkman B, Schwartz R, Matetzky S, Lubetsky A et al (2008) Aspirin responsiveness in acute brain ischaemia: association with stroke severity and clinical outcome. Cerebrovasc Dis 25:355–361. doi:10.​1159/​000118382 CrossRefPubMed
25.
Zurück zum Zitat Han SW, Kim SH, Lee JY, Chu CK, Yang JH, Shin HY et al (2007) A new subtype classification of ischemic stroke based on treatment and etiologic mechanism. Eur Neurol 57:96–102. doi:10.1159/000098059 CrossRefPubMed Han SW, Kim SH, Lee JY, Chu CK, Yang JH, Shin HY et al (2007) A new subtype classification of ischemic stroke based on treatment and etiologic mechanism. Eur Neurol 57:96–102. doi:10.​1159/​000098059 CrossRefPubMed
26.
Zurück zum Zitat Yi X, Zhou Q, Lin J, Chi L, Han Z (2013) Platelet response to aspirin in Chinese stroke patients is independent of genetic polymorphisms of COX-1 C50T and COX-2 G765C. J Atheroscler Thromb 20:65–72CrossRefPubMed Yi X, Zhou Q, Lin J, Chi L, Han Z (2013) Platelet response to aspirin in Chinese stroke patients is independent of genetic polymorphisms of COX-1 C50T and COX-2 G765C. J Atheroscler Thromb 20:65–72CrossRefPubMed
27.
29.
31.
Zurück zum Zitat Yi X, Chi W, Wang C, Zhang B, Lin J (2015) Low-molecular-weight heparin or dual antiplatelet therapy is more effective than aspirin alone in preventing early neurological deterioration and improving the 6-month outcome in ischemic stroke patients. J Clin Neurol 11:57–65. doi:10.3988/jcn.2015.11.1.57 CrossRefPubMedPubMedCentral Yi X, Chi W, Wang C, Zhang B, Lin J (2015) Low-molecular-weight heparin or dual antiplatelet therapy is more effective than aspirin alone in preventing early neurological deterioration and improving the 6-month outcome in ischemic stroke patients. J Clin Neurol 11:57–65. doi:10.​3988/​jcn.​2015.​11.​1.​57 CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Smock KJ, Saunders PJ, Rodgers GM, Johari V (2011) Laboratory evaluation of clopidogrel responsiveness by platelet function and genetic methods. Am J Hematol 86:1032–1034. doi:10.1002/ajh.22112 CrossRefPubMed Smock KJ, Saunders PJ, Rodgers GM, Johari V (2011) Laboratory evaluation of clopidogrel responsiveness by platelet function and genetic methods. Am J Hematol 86:1032–1034. doi:10.​1002/​ajh.​22112 CrossRefPubMed
34.
Zurück zum Zitat Lordkipanidze M, Pharand C, Schampaert E, Turgeon J, Palisaitis DA, Diodati JG (2007) A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease. Eur Heart J 28:1702–1708. doi:10.1093/eurheartj/ehm226 CrossRefPubMed Lordkipanidze M, Pharand C, Schampaert E, Turgeon J, Palisaitis DA, Diodati JG (2007) A comparison of six major platelet function tests to determine the prevalence of aspirin resistance in patients with stable coronary artery disease. Eur Heart J 28:1702–1708. doi:10.​1093/​eurheartj/​ehm226 CrossRefPubMed
35.
Zurück zum Zitat Cuisset T, Frere C, Poyet R, Quilici J, Gaborit B, Bali L et al (2010) Clopidogrel response: head-to-head comparison of different platelet assays to identify clopidogrel non responder patients after coronary stenting. Arch Cardiovasc Dis 103:39–45. doi:10.1016/j.acvd.2009.11.004 CrossRefPubMed Cuisset T, Frere C, Poyet R, Quilici J, Gaborit B, Bali L et al (2010) Clopidogrel response: head-to-head comparison of different platelet assays to identify clopidogrel non responder patients after coronary stenting. Arch Cardiovasc Dis 103:39–45. doi:10.​1016/​j.​acvd.​2009.​11.​004 CrossRefPubMed
36.
Zurück zum Zitat Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Meneveau N et al (2009) Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 360:363–375. doi:10.1056/NEJMoa0808227 CrossRefPubMed Simon T, Verstuyft C, Mary-Krause M, Quteineh L, Drouet E, Meneveau N et al (2009) Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med 360:363–375. doi:10.​1056/​NEJMoa0808227 CrossRefPubMed
39.
Zurück zum Zitat Marquardt L, Ruf A, Mansmann U, Winter R, Schuler M, Buggle F et al (2002) Course of platelet activation markers after ischemic stroke. Stroke 33:2570–2574CrossRefPubMed Marquardt L, Ruf A, Mansmann U, Winter R, Schuler M, Buggle F et al (2002) Course of platelet activation markers after ischemic stroke. Stroke 33:2570–2574CrossRefPubMed
40.
Zurück zum Zitat Marcus AJ, Safier LB, Broekman MJ, Islam N, Fliessbach JH, Hajjar KA et al (1995) Thrombosis and inflammation as multicellular processes: significance of cell-cell interactions. Thromb Haemost 74:213–217PubMed Marcus AJ, Safier LB, Broekman MJ, Islam N, Fliessbach JH, Hajjar KA et al (1995) Thrombosis and inflammation as multicellular processes: significance of cell-cell interactions. Thromb Haemost 74:213–217PubMed
41.
Zurück zum Zitat Fateh-Moghadam S, Li Z, Ersel S, Reuter T, Htun P, Plockinger U et al (2005) Platelet degranulation is associated with progression of intima-media thickness of the common carotid artery in patients with diabetes mellitus type 2. Arterioscler Thromb Vasc Biol 25:1299–1303CrossRefPubMed Fateh-Moghadam S, Li Z, Ersel S, Reuter T, Htun P, Plockinger U et al (2005) Platelet degranulation is associated with progression of intima-media thickness of the common carotid artery in patients with diabetes mellitus type 2. Arterioscler Thromb Vasc Biol 25:1299–1303CrossRefPubMed
42.
Zurück zum Zitat Serena J, Rodriguez-Yanez M, Castellanos M (2006) Deterioration in acute ischemic stroke as the target for neuroprotection. Cerebrovasc Dis 21(Suppl. 2):40–48 Serena J, Rodriguez-Yanez M, Castellanos M (2006) Deterioration in acute ischemic stroke as the target for neuroprotection. Cerebrovasc Dis 21(Suppl. 2):40–48
43.
Zurück zum Zitat Zhang X, Sun Z, Ding C, Tang Y, Jiang X, Xie Y et al (2016) Metabolic syndrome augments the risk of early neurological deterioration in acute ischemic stroke patients independent of inflammatory mediators: a hospital-based prospective study. Oxid Med Cell Longev 2016:8346301. doi:10.1155/2016/8346301 PubMedPubMedCentral Zhang X, Sun Z, Ding C, Tang Y, Jiang X, Xie Y et al (2016) Metabolic syndrome augments the risk of early neurological deterioration in acute ischemic stroke patients independent of inflammatory mediators: a hospital-based prospective study. Oxid Med Cell Longev 2016:8346301. doi:10.​1155/​2016/​8346301 PubMedPubMedCentral
44.
46.
Zurück zum Zitat Meigs JB, Mittleman MA, Nathan DM, Tofler GH, Singer DE, Murphy-Sheehy PM et al (2000) Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study. JAMA 283:221–228CrossRefPubMed Meigs JB, Mittleman MA, Nathan DM, Tofler GH, Singer DE, Murphy-Sheehy PM et al (2000) Hyperinsulinemia, hyperglycemia, and impaired hemostasis: the Framingham Offspring Study. JAMA 283:221–228CrossRefPubMed
47.
Zurück zum Zitat Erlinge D, Varenhorst C, Braun OO, James S, Winters KJ, Jakubowski JA et al (2008) Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo. J Am Coll Cardiol 52:1968–1977. doi:10.1016/j.jacc.2008.07.068 CrossRefPubMed Erlinge D, Varenhorst C, Braun OO, James S, Winters KJ, Jakubowski JA et al (2008) Patients with poor responsiveness to thienopyridine treatment or with diabetes have lower levels of circulating active metabolite, but their platelets respond normally to active metabolite added ex vivo. J Am Coll Cardiol 52:1968–1977. doi:10.​1016/​j.​jacc.​2008.​07.​068 CrossRefPubMed
48.
49.
Zurück zum Zitat Depta JP, Fowler J, Novak E, Katzan I, Bakdash S, Kottke-Marchant K et al (2012) Clinical outcomes using a platelet function-guided approach for secondary prevention in patients with ischemic stroke or transient ischemic attack. Stroke 43:2376–2381. doi:10.1161/STROKEAHA CrossRefPubMed Depta JP, Fowler J, Novak E, Katzan I, Bakdash S, Kottke-Marchant K et al (2012) Clinical outcomes using a platelet function-guided approach for secondary prevention in patients with ischemic stroke or transient ischemic attack. Stroke 43:2376–2381. doi:10.​1161/​STROKEAHA CrossRefPubMed
50.
Zurück zum Zitat Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB et al (2010) Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet 376:1233–1243. doi:10.1016/S0140-6736(10)61088-4 CrossRefPubMed Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB et al (2010) Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial. Lancet 376:1233–1243. doi:10.​1016/​S0140-6736(10)61088-4 CrossRefPubMed
51.
Zurück zum Zitat Helgason CM, Tortorice KL, Winkler SR, Penney DW, Schuler JJ, McClelland TJ et al (1993) Aspirin response and failure in cerebral infarction. Stroke 24:345–350CrossRefPubMed Helgason CM, Tortorice KL, Winkler SR, Penney DW, Schuler JJ, McClelland TJ et al (1993) Aspirin response and failure in cerebral infarction. Stroke 24:345–350CrossRefPubMed
Metadaten
Titel
Antiplatelet drug resistance is associated with early neurological deterioration in acute minor ischemic stroke in the Chinese population
verfasst von
Xingyang Yi
Chun Wang
Ping Liu
Cheng Fu
Jing Lin
Yiming Chen
Publikationsdatum
03.06.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Neurology / Ausgabe 8/2016
Print ISSN: 0340-5354
Elektronische ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-016-8181-5

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