Thromb Haemost 2018; 118(12): 2145-2151
DOI: 10.1055/s-0038-1675602
Stroke, Systemic or Venous Thromboembolism
Georg Thieme Verlag KG Stuttgart · New York

Stroke Severity in Patients on Non-Vitamin K Antagonist Oral Anticoagulants with a Standard or Insufficient Dose

Yo Han Jung
1   Department of Neurology, Changwon Fatima Hospital, Changwon, Korea
,
Hye-Yeon Choi
2   Department of Neurology, Kyung Hee University School of Medicine, Kyung Hee University Hospital at Gangdong, Seoul, Korea
,
Kyung-Yul Lee
3   Department of Neurology, Gangnam Severance Hospital, Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea
,
Kyeongyeol Cheon
3   Department of Neurology, Gangnam Severance Hospital, Severance Institute for Vascular and Metabolic Research, Yonsei University College of Medicine, Seoul, Korea
,
Sang Won Han
4   Department of Neurology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
,
Joong Hyun Park
4   Department of Neurology, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
,
Han-Jin Cho
5   Department of Neurology, Pusan National University Hospital, Pusan National University College of Medicine and Biomedical Research Institute, Busan, Korea
,
Hyung Jong Park
6   Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
,
Hyo Suk Nam
6   Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
,
Ji Hoe Heo
6   Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
,
Hye Sun Lee
7   Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, Korea
,
Young Dae Kim
6   Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
› Institutsangaben
Funding This work was supported by a grant of the Korea Heath Technology R&D Project through the Korea Health Industry Development (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI08C2149) and a faculty research grant from the Yonsei University College of Medicine (6–2017–0128).
Weitere Informationen

Publikationsverlauf

06. Juli 2018

22. September 2018

Publikationsdatum:
19. November 2018 (online)

Abstract

Background The stroke severity or functional outcomes could differ because the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) could be different according to the dose. We investigated whether there was any difference in the stroke outcomes in patients with non-valvular atrial fibrillation (NVAF) by their prior medication status, including standard-dosed versus under-dosed NOACs.

Materials and Methods We enrolled 858 patients with acute ischaemic stroke with chronic NVAF admitted at six hospitals in Korea. We categorized their prior medication status as follows: (1) no anti-thrombotics (n = 219), (2) only anti-platelet (n = 347), (3) warfarin with a sub-therapeutic intensity (n = 185), (4) warfarin with a therapeutic intensity (n = 37), (5) under-dosed NOAC (n = 27) and (6) standard-dosed NOAC (n = 43). We compared the initial stroke severity between groups.

Results Among the 858 patients, the patients on standard-dosed NOACs had the lowest initial National Institute of Health Stroke Scale (NIHSS) score, followed by those on warfarin with a therapeutic intensity and those on only anti-platelet (p < 0.05). Multivariate analysis demonstrated that the NIHSS score was significantly low in the patients on warfarin with a therapeutic intensity (B, –5.602; 95% confidence interval [CI], –8.636 to –2.568; p < 0.001) or those on standard-dosed NOACs (B, –3.588; 95% CI, –6.405 to –0.771; p = 0.013), while there was no difference in the NIHSS score between the patients not taking any anti-thrombotics and those on warfarin with a sub-therapeutic intensity or under-dosed NOACs.

Conclusion Use of warfarin with a therapeutic intensity or standard-dosed NOACs was associated with a relatively mild stroke in the patients with NVAF.

Supplementary Material

 
  • References

  • 1 Cardiogenic brain embolism. Cerebral Embolism Task Force. Arch Neurol 1986; 43 (01) 71-84
  • 2 Han SW, Nam HS, Kim SH, Lee JY, Lee KY, Heo JH. Frequency and significance of cardiac sources of embolism in the TOAST classification. Cerebrovasc Dis 2007; 24 (05) 463-468
  • 3 Lin HJ, Wolf PA, Kelly-Hayes M. , et al. Stroke severity in atrial fibrillation. The Framingham Study. Stroke 1996; 27 (10) 1760-1764
  • 4 Aguilar MI, Hart R. Oral anticoagulants for preventing stroke in patients with non-valvular atrial fibrillation and no previous history of stroke or transient ischemic attacks. Cochrane Database Syst Rev 2005; (03) CD001927
  • 5 Kim YD, Lee KY, Nam HS. , et al. Factors associated with ischemic stroke on therapeutic anticoagulation in patients with nonvalvular atrial fibrillation. Yonsei Med J 2015; 56 (02) 410-417
  • 6 Hylek EM, Go AS, Chang Y. , et al. Effect of intensity of oral anticoagulation on stroke severity and mortality in atrial fibrillation. N Engl J Med 2003; 349 (11) 1019-1026
  • 7 O'Donnell M, Oczkowski W, Fang J. , et al; Investigators of the Registry of the Canadian Stroke Network. Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study. Lancet Neurol 2006; 5 (09) 749-754
  • 8 Xian Y, O'Brien EC, Liang L. , et al. Association of preceding antithrombotic treatment with acute ischemic stroke severity and in-hospital outcomes among patients with atrial fibrillation. JAMA 2017; 317 (10) 1057-1067
  • 9 Tomita H, Hagii J, Metoki N. , et al. Severity and functional outcome of patients with cardioembolic stroke occurring during non-vitamin K antagonist oral anticoagulant treatment. J Stroke Cerebrovasc Dis 2015; 24 (06) 1430-1437
  • 10 Hellwig S, Grittner U, Audebert H, Endres M, Haeusler KG. Non-vitamin K-dependent oral anticoagulants have a positive impact on ischaemic stroke severity in patients with atrial fibrillation. Europace 2018; 20 (04) 569-574
  • 11 Kim WJ, Park JM, Kang K. , et al. Adherence to guidelines for antithrombotic therapy in patients with atrial fibrillation according to CHADS2 score before and after stroke: a multicenter observational study from Korea. J Clin Neurol 2016; 12 (01) 34-41
  • 12 Lee IH, Kim H, Je NK. Underutilization of warfarin for stroke prophylaxis in patients with atrial fibrillation or atrial flutter in Korea. J Cardiol 2015; 66 (06) 475-481
  • 13 Choi EJ, Lee IH, Je NK. Inadequate stroke prevention in Korean atrial fibrillation patients in the post-warfarin era. Int J Cardiol 2016; 220: 647-652
  • 14 Choi HY, Cha MJ, Nam HS, Kim YD, Hong KS, Heo JH. ; Korean Stroke Unit Study Collaborators. Stroke units and stroke care services in Korea. Int J Stroke 2012; 7 (04) 336-340
  • 15 Kim YD, Jung YH, Saposnik G. Traditional risk factors for stroke in East Asia. J Stroke 2016; 18 (03) 273-285
  • 16 Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the euro heart survey on atrial fibrillation. Chest 2010; 137 (02) 263-272
  • 17 Hong KS, Lee J, Bae HJ. , et al. Greater stroke severity predominates over all other factors for the worse outcome of cardioembolic stroke. J Stroke Cerebrovasc Dis 2013; 22 (08) e373-e380
  • 18 Adams Jr HP, Bendixen BH, Kappelle LJ. , et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke 1993; 24 (01) 35-41
  • 19 Tobin J. Estimation of relationships for limited dependent variables. Econometrica 1958; 26 (01) 24-36
  • 20 Başaran Ö, Dogan V, Beton O. , et al; Collaborators. Suboptimal use of non-vitamin K antagonist oral anticoagulants: results from the RAMSES study. Medicine (Baltimore) 2016; 95 (35) e4672
  • 21 Pugh D, Pugh J, Mead GE. Attitudes of physicians regarding anticoagulation for atrial fibrillation: a systematic review. Age Ageing 2011; 40 (06) 675-683
  • 22 Barra ME, Fanikos J, Connors JM, Sylvester KW, Piazza G, Goldhaber SZ. Evaluation of dose-reduced direct oral anticoagulant therapy. Am J Med 2016; 129 (11) 1198-1204
  • 23 Miller VT, Pearce LA, Feinberg WM, Rothrock JF, Anderson DC, Hart RG. ; Stroke Prevention in Atrial Fibrillation Investigators. Differential effect of aspirin versus warfarin on clinical stroke types in patients with atrial fibrillation. Neurology 1996; 46 (01) 238-240
  • 24 Watson T, Shantsila E, Lip GY. Mechanisms of thrombogenesis in atrial fibrillation: Virchow's triad revisited. Lancet 2009; 373 (9658): 155-166
  • 25 Yao X, Shah ND, Sangaralingham LR, Gersh BJ, Noseworthy PA. Non-vitamin K antagonist oral anticoagulant dosing in patients with atrial fibrillation and renal dysfunction. J Am Coll Cardiol 2017; 69 (23) 2779-2790
  • 26 Wang KL, Giugliano RP, Goto S. , et al. Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: a meta-analysis of contemporary randomized controlled trials. Heart Rhythm 2016; 13 (12) 2340-2347
  • 27 Hori M, Connolly SJ, Zhu J. , et al; RE-LY Investigators. Dabigatran versus warfarin: effects on ischemic and hemorrhagic strokes and bleeding in Asians and non-Asians with atrial fibrillation. Stroke 2013; 44 (07) 1891-1896
  • 28 Wang KL, Lip GY, Lin SJ, Chiang CE. Non-vitamin K antagonist oral anticoagulants for stroke prevention in Asian patients with nonvalvular atrial fibrillation: meta-analysis. Stroke 2015; 46 (09) 2555-2561
  • 29 Lip GY, Wang KL, Chiang CE. Non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention in Asian patients with atrial fibrillation: time for a reappraisal. Int J Cardiol 2015; 180: 246-254
  • 30 Shimomura D, Nakagawa Y, Kondo H. , et al. Relationship between plasma dabigatran concentration and activated partial thromboplastin time in Japanese patients with non-valvular atrial fibrillation. J Arrhythm 2015; 31 (04) 183-188
  • 31 Kawabata M, Yokoyama Y, Sasano T. , et al. Bleeding events and activated partial thromboplastin time with dabigatran in clinical practice. J Cardiol 2013; 62 (02) 121-126