Skip to main content
Top
Published in: Journal of Thrombosis and Thrombolysis 4/2016

01-11-2016

Safety and efficacy of non-vitamin K oral anticoagulant treatment compared with warfarin in patients with non-valvular atrial fibrillation who develop acute ischemic stroke or transient ischemic attack: a multicenter prospective cohort study (daVinci study)

Authors: Naoki Saji, Kazumi Kimura, Yohei Tateishi, Shigeru Fujimoto, Nobuyuki Kaneko, Takao Urabe, Akira Tsujino, Yasuyuki Iguchi, daVinci Study Group

Published in: Journal of Thrombosis and Thrombolysis | Issue 4/2016

Login to get access

Abstract

The safety and efficacy of non-vitamin K oral anticoagulant (NOAC) compared with warfarin in treating patients with non-valvular atrial fibrillation (NVAF) who developed acute ischemic stroke or transient ischemic attack (AIS/TIA), particularly those receiving tissue-plasminogen activator (tPA) therapy, remains unclear. Between April 2012 and December 2014, we conducted a multicenter prospective cohort study to assess the current clinical practice for treating such patients. We divided the patients into two groups according to the administration of oral anticoagulants (warfarin or NOACs) and tPA therapy. The risk of any hemorrhagic or ischemic event was compared within 1 month after the onset of stroke. We analyzed 235 patients with AIS/TIA including 73 who received tPA therapy. Oral anticoagulants were initiated within 2–4 inpatient days. NOACs were administered to 49.8 % of patients, who were predominantly male, younger, had small infarcts, lower NIHSS scores, and had a lower all-cause mortality rate (0 vs. 4.2 %, P = 0.06) and a lower risk of any ischemic events (6.0 vs. 7.6 %, P = 0.797) compared with warfarin users. The prevalence of all hemorrhagic events was equivalent between the two groups. Early initiation of NOACs after tPA therapy appeared to lower the risk of hemorrhagic events, although there was no significant difference (0 vs. 5.6 %, P = 0.240). Although more clinicians are apt to prescribe NOACs in minor ischemic stroke, NOAC treatment may provide a potential benefit in such cases. Early initiation of NOACs after tPA therapy may reduce the risk of hemorrhagic events compared with warfarin.
Appendix
Available only for authorised users
Literature
1.
go back to reference Saji N, Kimura K, Ohsaka G, Higashi Y, Teramoto Y, Usui M, Kita Y (2015) Functional independence measure scores predict level of long-term care required by patients after stroke: a multicenter retrospective cohort study. Disabil Rehabil 37:331–337CrossRefPubMed Saji N, Kimura K, Ohsaka G, Higashi Y, Teramoto Y, Usui M, Kita Y (2015) Functional independence measure scores predict level of long-term care required by patients after stroke: a multicenter retrospective cohort study. Disabil Rehabil 37:331–337CrossRefPubMed
2.
go back to reference Kimura K, Kazui S, Minematsu K, Yamaguchi T, Japan Multicenter Stroke Investigator’s Collaboration (2004) Analysis of 16,922 patients with acute ischemic stroke and transient ischemic attack in Japan. A hospital-based prospective registration study. Cerebrovasc Dis 18:47–56CrossRefPubMed Kimura K, Kazui S, Minematsu K, Yamaguchi T, Japan Multicenter Stroke Investigator’s Collaboration (2004) Analysis of 16,922 patients with acute ischemic stroke and transient ischemic attack in Japan. A hospital-based prospective registration study. Cerebrovasc Dis 18:47–56CrossRefPubMed
3.
go back to reference Kimura K, Minematsu K, Yamaguchi T, Japan Multicenter Stroke Investigators’ Collaboration (J-MUSIC) (2005) Atrial fibrillation as a predictive factor for severe stroke and early death in 15,831 patients with acute ischaemic stroke. J Neurol Neurosurg Psychiatr 76:679–683CrossRefPubMedPubMedCentral Kimura K, Minematsu K, Yamaguchi T, Japan Multicenter Stroke Investigators’ Collaboration (J-MUSIC) (2005) Atrial fibrillation as a predictive factor for severe stroke and early death in 15,831 patients with acute ischaemic stroke. J Neurol Neurosurg Psychiatr 76:679–683CrossRefPubMedPubMedCentral
4.
go back to reference Kato Y, Hayashi T, Tanahashi N, Kobayashi S, Japan Standard Stroke Registry Study Group (2015) Cardioembolic stroke is the most serious problem in the aging society: Japan standard stroke registry study. J Stroke Cerebrovasc Dis 24:811–814CrossRefPubMed Kato Y, Hayashi T, Tanahashi N, Kobayashi S, Japan Standard Stroke Registry Study Group (2015) Cardioembolic stroke is the most serious problem in the aging society: Japan standard stroke registry study. J Stroke Cerebrovasc Dis 24:811–814CrossRefPubMed
5.
go back to reference Iguchi Y, Kimura K, Aoki J, Kobayashi K, Terasawa Y, Sakai K, Shibazaki K (2008) Prevalence of atrial fibrillation in community-dwelling japanese aged 40 years or older in Japan: analysis of 41,436 non-employee residents in Kurashiki-city. Circ J 72:909–913CrossRefPubMed Iguchi Y, Kimura K, Aoki J, Kobayashi K, Terasawa Y, Sakai K, Shibazaki K (2008) Prevalence of atrial fibrillation in community-dwelling japanese aged 40 years or older in Japan: analysis of 41,436 non-employee residents in Kurashiki-city. Circ J 72:909–913CrossRefPubMed
6.
go back to reference Schnabel RB, Yin X, Gona P, Larson MG, Beiser AS, McManus DD, Newton-Cheh C, Lubitz SA, Magnani JW, Ellinor PT, Seshadri S, Wolf PA, Vasan RS, Benjamin EJ, Levy D (2015) 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet 386:154–162CrossRefPubMedPubMedCentral Schnabel RB, Yin X, Gona P, Larson MG, Beiser AS, McManus DD, Newton-Cheh C, Lubitz SA, Magnani JW, Ellinor PT, Seshadri S, Wolf PA, Vasan RS, Benjamin EJ, Levy D (2015) 50 year trends in atrial fibrillation prevalence, incidence, risk factors, and mortality in the Framingham Heart Study: a cohort study. Lancet 386:154–162CrossRefPubMedPubMedCentral
7.
go back to reference Xian Y, Wu J, O’Brien EC, Fonarow GC, Olson DM, Schwamm LH, Bhatt DL, Smith EE, Suter RE, Hannah D, Lindholm B, Maisch L, Greiner MA, Lytle BL, Pencina MJ, Peterson ED, Hernandez AF (2015) Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: observational analysis from Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study. BMJ 351:h3786CrossRefPubMedPubMedCentral Xian Y, Wu J, O’Brien EC, Fonarow GC, Olson DM, Schwamm LH, Bhatt DL, Smith EE, Suter RE, Hannah D, Lindholm B, Maisch L, Greiner MA, Lytle BL, Pencina MJ, Peterson ED, Hernandez AF (2015) Real world effectiveness of warfarin among ischemic stroke patients with atrial fibrillation: observational analysis from Patient-Centered Research into Outcomes Stroke Patients Prefer and Effectiveness Research (PROSPER) study. BMJ 351:h3786CrossRefPubMedPubMedCentral
8.
go back to reference Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ (2012) Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. Am J Cardiol 110:453–460CrossRefPubMed Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ (2012) Meta-analysis of efficacy and safety of new oral anticoagulants (dabigatran, rivaroxaban, apixaban) versus warfarin in patients with atrial fibrillation. Am J Cardiol 110:453–460CrossRefPubMed
9.
go back to reference Verheugt FW, Granger CB (2015) Oral anticoagulants for stroke prevention in atrial fibrillation: current status, special situations, and unmet needs. Lancet 386:303–310CrossRefPubMed Verheugt FW, Granger CB (2015) Oral anticoagulants for stroke prevention in atrial fibrillation: current status, special situations, and unmet needs. Lancet 386:303–310CrossRefPubMed
10.
go back to reference Senoo K, Lau YC, Dzeshka M, Lane D, Okumura K, Lip GY (2015) Efficacy and safety of non-vitamin K antagonist oral anticoagulants vs. warfarin in Japanese patients with atrial fibrillation—meta-analysis. Circ J 79:339–345CrossRefPubMed Senoo K, Lau YC, Dzeshka M, Lane D, Okumura K, Lip GY (2015) Efficacy and safety of non-vitamin K antagonist oral anticoagulants vs. warfarin in Japanese patients with atrial fibrillation—meta-analysis. Circ J 79:339–345CrossRefPubMed
11.
go back to reference Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383:955–962CrossRefPubMed Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, Yamashita T, Antman EM (2014) Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 383:955–962CrossRefPubMed
12.
go back to reference Toyoda K, Arihiro S, Todo K, Yamagami H, Kimura K, Furui E, Terasaki T, Shiokawa Y, Kamiyama K, Takizawa S, Okuda S, Okada Y, Kameda T, Nagakane Y, Hasegawa Y, Mochizuki H, Ito Y, Nakashima T, Takamatsu K, Nishiyama K, Kario K, Sato S, Koga M, SAMURAI Study Investigators (2015) Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: the SAMURAI-NVAF study. Int J Stroke 10:836–842CrossRefPubMedPubMedCentral Toyoda K, Arihiro S, Todo K, Yamagami H, Kimura K, Furui E, Terasaki T, Shiokawa Y, Kamiyama K, Takizawa S, Okuda S, Okada Y, Kameda T, Nagakane Y, Hasegawa Y, Mochizuki H, Ito Y, Nakashima T, Takamatsu K, Nishiyama K, Kario K, Sato S, Koga M, SAMURAI Study Investigators (2015) Trends in oral anticoagulant choice for acute stroke patients with nonvalvular atrial fibrillation in Japan: the SAMURAI-NVAF study. Int J Stroke 10:836–842CrossRefPubMedPubMedCentral
13.
go back to reference Nomura E, Ohshita T, Imamura E, Wakabayashi S, Kajikawa H, Hosomi N, Matsumoto M (2015) Early administration of non-vitamin K antagonist oral anticoagulants for acute ischemic stroke patients with atrial fibrillation in comparison with warfarin mostly combined with heparin. Circ J 79:862–866CrossRefPubMed Nomura E, Ohshita T, Imamura E, Wakabayashi S, Kajikawa H, Hosomi N, Matsumoto M (2015) Early administration of non-vitamin K antagonist oral anticoagulants for acute ischemic stroke patients with atrial fibrillation in comparison with warfarin mostly combined with heparin. Circ J 79:862–866CrossRefPubMed
14.
15.
go back to reference Shibazaki K, Kimura K, Aoki J, Saji N, Sakai K (2013) Early initiation of new oral anticoagulants in acute stroke and TIA patients with nonvalvular atrial fibrillation. J Neurol Sci 331:90–93CrossRefPubMed Shibazaki K, Kimura K, Aoki J, Saji N, Sakai K (2013) Early initiation of new oral anticoagulants in acute stroke and TIA patients with nonvalvular atrial fibrillation. J Neurol Sci 331:90–93CrossRefPubMed
16.
go back to reference European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH (2010) Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 31:2369–2429CrossRef European Heart Rhythm Association, European Association for Cardio-Thoracic Surgery, Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH (2010) Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J 31:2369–2429CrossRef
17.
go back to reference Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, European Heart Rhythm Association (2013) European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 15:625–651CrossRefPubMed Heidbuchel H, Verhamme P, Alings M, Antz M, Hacke W, Oldgren J, Sinnaeve P, Camm AJ, Kirchhof P, European Heart Rhythm Association (2013) European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 15:625–651CrossRefPubMed
18.
go back to reference Lip GY, Wang KL, Chiang CE (2015) Non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in Asian patients with atrial fibrillation: time for a reappraisal. Int J Cardiol 180:246–254CrossRefPubMed Lip GY, Wang KL, Chiang CE (2015) Non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in Asian patients with atrial fibrillation: time for a reappraisal. Int J Cardiol 180:246–254CrossRefPubMed
19.
go back to reference Shen AY, Yao JF, Brar SS, Jorgensen MB, Chen W (2007) Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. J Am Coll Cardiol 50:309–315CrossRefPubMed Shen AY, Yao JF, Brar SS, Jorgensen MB, Chen W (2007) Racial/ethnic differences in the risk of intracranial hemorrhage among patients with atrial fibrillation. J Am Coll Cardiol 50:309–315CrossRefPubMed
20.
go back to reference Abraham NS, Singh S, Alexander GC, Heien H, Haas LR, Crown W, Shah ND (2015) Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ 350:h1857CrossRefPubMedPubMedCentral Abraham NS, Singh S, Alexander GC, Heien H, Haas LR, Crown W, Shah ND (2015) Comparative risk of gastrointestinal bleeding with dabigatran, rivaroxaban, and warfarin: population based cohort study. BMJ 350:h1857CrossRefPubMedPubMedCentral
21.
go back to reference Hernandez I, Baik SH, Piñera A, Zhang Y (2015) Risk of bleeding with dabigatran in atrial fibrillation. JAMA Intern Med 175:18–24CrossRefPubMed Hernandez I, Baik SH, Piñera A, Zhang Y (2015) Risk of bleeding with dabigatran in atrial fibrillation. JAMA Intern Med 175:18–24CrossRefPubMed
22.
go back to reference Saji N, Kimura K, Aoki J, Uemura J, Sakamoto Y (2015) Intracranial hemorrhage caused by non-vitamin K antagonist oral anticoagulants (NOACs). Circ J 79:1018–1023CrossRefPubMed Saji N, Kimura K, Aoki J, Uemura J, Sakamoto Y (2015) Intracranial hemorrhage caused by non-vitamin K antagonist oral anticoagulants (NOACs). Circ J 79:1018–1023CrossRefPubMed
23.
go back to reference Caldeira D, Barra M, Pinto FJ, Ferreira JJ, Costa J (2015) Intracranial hemorrhage risk with the new oral anticoagulants: a systematic review and meta-analysis. J Neurol 262:516–522CrossRefPubMed Caldeira D, Barra M, Pinto FJ, Ferreira JJ, Costa J (2015) Intracranial hemorrhage risk with the new oral anticoagulants: a systematic review and meta-analysis. J Neurol 262:516–522CrossRefPubMed
24.
go back to reference Sardar P, Chatterjee S, Chaudhari S, Lip GY (2014) New oral anticoagulants in elderly adults: evidence from a meta-analysis of randomized trials. J Am Geriatr Soc 62:857–864CrossRefPubMed Sardar P, Chatterjee S, Chaudhari S, Lip GY (2014) New oral anticoagulants in elderly adults: evidence from a meta-analysis of randomized trials. J Am Geriatr Soc 62:857–864CrossRefPubMed
25.
go back to reference Hong KS, Choi YJ, Kwon SU, Triple AXEL Investigators (2015) Rationale and design of Triple AXEL: trial for early anticoagulation in acute ischemic stroke patients with nonvalvular atrial fibrillation. Int J Stroke 10:128–133CrossRefPubMed Hong KS, Choi YJ, Kwon SU, Triple AXEL Investigators (2015) Rationale and design of Triple AXEL: trial for early anticoagulation in acute ischemic stroke patients with nonvalvular atrial fibrillation. Int J Stroke 10:128–133CrossRefPubMed
26.
go back to reference Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, Garcia DA, Jacobson A, Jaffer AK, Kong DF, Schulman S, Turpie AG, Hasselblad V, Ortel TL (2015) BRIDGE Investigators: perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 373:823–833CrossRefPubMedPubMedCentral Douketis JD, Spyropoulos AC, Kaatz S, Becker RC, Caprini JA, Dunn AS, Garcia DA, Jacobson A, Jaffer AK, Kong DF, Schulman S, Turpie AG, Hasselblad V, Ortel TL (2015) BRIDGE Investigators: perioperative bridging anticoagulation in patients with atrial fibrillation. N Engl J Med 373:823–833CrossRefPubMedPubMedCentral
27.
go back to reference Aoki J, Kimura K, Shibazaki K, Saji N, Uemura J, Sakamoto Y, Nagai K (2015) The susceptibility vessel sign at the proximal M1: a strong predictor for poor outcome after intravenous thrombolysis. J Neurol Sci 348:195–200CrossRefPubMed Aoki J, Kimura K, Shibazaki K, Saji N, Uemura J, Sakamoto Y, Nagai K (2015) The susceptibility vessel sign at the proximal M1: a strong predictor for poor outcome after intravenous thrombolysis. J Neurol Sci 348:195–200CrossRefPubMed
Metadata
Title
Safety and efficacy of non-vitamin K oral anticoagulant treatment compared with warfarin in patients with non-valvular atrial fibrillation who develop acute ischemic stroke or transient ischemic attack: a multicenter prospective cohort study (daVinci study)
Authors
Naoki Saji
Kazumi Kimura
Yohei Tateishi
Shigeru Fujimoto
Nobuyuki Kaneko
Takao Urabe
Akira Tsujino
Yasuyuki Iguchi
daVinci Study Group
Publication date
01-11-2016
Publisher
Springer US
Published in
Journal of Thrombosis and Thrombolysis / Issue 4/2016
Print ISSN: 0929-5305
Electronic ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-016-1376-x

Other articles of this Issue 4/2016

Journal of Thrombosis and Thrombolysis 4/2016 Go to the issue