Thromb Haemost 2018; 118(03): 572-580
DOI: 10.1055/s-0038-1627454
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH Stuttgart

Anticoagulants Resumption after Warfarin-Related Intracerebral Haemorrhage: The Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy)

Loris Poli
,
Mario Grassi
,
Marialuisa Zedde
,
Simona Marcheselli
,
Giorgio Silvestrelli
,
Maria Sessa
,
Andrea Zini
,
Maurizio Paciaroni
,
Cristiano Azzini
,
Massimo Gamba
,
Antonella Toriello
,
Rossana Tassi
,
Elisa Giorli
,
Rocco Salvatore Calabrò
,
Marco Ritelli
,
Alessandro De Vito
,
Nicola Pugliese
,
Giuseppe Martini
,
Alessia Lanari
,
Corrado Lodigiani
,
Marina Padroni
,
Valeria De Giuli
,
Filomena Caria
,
Andrea Morotti
,
Paolo Costa
,
Davide Strambo
,
Manuel Corato
,
Rosario Pascarella
,
Massimo Del Sette
,
Giovanni Malferrari
,
Marina Colombi
,
Alessandro Padovani
,
Alessandro Pezzini
,
on behalf of the Multicenter Study on Cerebral Hemorrhage in Italy (MUCH-Italy) Investigators
Further Information

Publication History

28 July 2017

21 December 2017

Publication Date:
12 February 2018 (online)

Abstract

Whether to resume antithrombotic treatment after oral anticoagulant–related intracerebral haemorrhage (OAC-ICH) is debatable. In this study, we aimed at investigating long-term outcome associated with OAC resumption after warfarin-related ICH, in comparison with secondary prevention strategies with platelet inhibitors or antithrombotic discontinuation. Participants were patients who sustained an incident ICH during warfarin treatment (2002–2014) included in the Multicenter Study on Cerebral Hemorrhage in Italy. Primary end-point was a composite of ischemic stroke/systemic embolism (SE) and all-cause mortality. Secondary end-points were ischemic stroke/SE, all-cause mortality and major recurrent bleeding. We computed individual propensity score (PS) as the probability that a patient resumes OACs or other agents given his pre-treatment variables, and performed Cox multivariable analysis using Inverse Probability of Treatment Weighting (IPTW) procedure. A total of 244 patients qualified for the analysis. Unlike antiplatelet agents, OAC resumption was associated with a lower rate of the primary end-point (weighted hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.09–0.45), as well as of overall mortality (weighted HR, 0.17; 95% CI, 0.06–0.45) and ischemic stroke/SE (weighted HR, 0.19; 95% CI, 0.06–0.60) with no significant increase of major bleeding in comparison with patients receiving no antithrombotics. In the subgroup of patients with atrial fibrillation, OACs resumption was also associated with a reduction of the primary end-point (weighted HR, 0.22; 95% CI, 0.09–0.54), and the secondary end-point ischemic stroke/SE (weighted HR, 0.09; 95% CI, 0.02–0.40). In conclusion, in patients who have an ICH while receiving warfarin, resuming anticoagulation results in a favorable trade-off between bleeding susceptibility and thromboembolic risk.

Supplementary Material

 
  • References

  • 1 Béjot Y, Cordonnier C, Durier J, Aboa-Eboulé C, Rouaud O, Giroud M. Intracerebral haemorrhage profiles are changing: results from the Dijon population-based study. Brain 2013; 136 (Pt 2): 658-664
  • 2 Flaherty ML, Kissela B, Woo D. , et al. The increasing incidence of anticoagulant-associated intracerebral hemorrhage. Neurology 2007; 68 (02) 116-121
  • 3 Friberg L, Rosenqvist M, Lip GYH. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J 2012; 33 (12) 1500-1510
  • 4 Poon MTC, Fonville AF, Al-Shahi Salman R. Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2014; 85 (06) 660-667
  • 5 Hemphill III JC, Greenberg SM, Anderson CS. , et al; American Heart Association Stroke Council; Council on Cardiovascular and Stroke Nursing; Council on Clinical Cardiology. Guidelines for the management of spontaneous intracerebral hemorrhage: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2015; 46 (07) 2032-2060
  • 6 Steiner T, Al-Shahi Salman R, Beer R. , et al; European Stroke Organisation. European Stroke Organisation (ESO) guidelines for the management of spontaneous intracerebral hemorrhage. Int J Stroke 2014; 9 (07) 840-855
  • 7 Pezzini A, Grassi M, Paciaroni M. , et al; Multicentre Study on Cerebral Hemorrhage in Italy (MUCH-Italy) Investigators. Obesity and the risk of intracerebral hemorrhage: the multicenter study on cerebral hemorrhage in Italy. Stroke 2013; 44 (06) 1584-1589
  • 8 Connolly SJ, Ezekowitz MD, Yusuf S. , et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009; 361 (12) 1139-1151
  • 9 Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika 1983; 70: 41-55
  • 10 Xu S, Ross C, Raebel MA, Shetterly S, Blanchette C, Smith D. Use of stabilized inverse propensity scores as weights to directly estimate relative risk and its confidence intervals. Value Health 2010; 13 (02) 273-277
  • 11 Murthy SB, Gupta A, Merkler AE. , et al. Restarting anticoagulant therapy after intracranial hemorrhage: a systematic review and meta-analysis. Stroke 2017; 48 (06) 1594-1600
  • 12 Biffi A, Anderson CD, Battey TW. , et al. Association between blood pressure control and risk of recurrent intracerebral hemorrhage. JAMA 2015; 314 (09) 904-912
  • 13 Biffi A, Kuramatsu JB, Leasure A. , et al. Oral anticoagulation and functional outcome after intracerebral hemorrhage. Ann Neurol 2017; 82 (05) 755-765
  • 14 Greenberg SM, Vernooij MW, Cordonnier C. , et al; Microbleed Study Group. Cerebral microbleeds: a guide to detection and interpretation. Lancet Neurol 2009; 8 (02) 165-174
  • 15 Korompoki E, Filippidis FT, Nielsen PB. , et al. Long-term antithrombotic treatment in intracranial hemorrhage survivors with atrial fibrillation. Neurology 2017; 89 (07) 687-696
  • 16 Nielsen PB, Larsen TB, Skjøth F, Gorst-Rasmussen A, Rasmussen LH, Lip GY. Restarting anticoagulant treatment after intracranial hemorrhage in patients with atrial fibrillation and the impact on recurrent stroke, mortality, and bleeding: a nationwide cohort study. Circulation 2015; 132 (06) 517-525
  • 17 Yung D, Kapral MK, Asllani E, Fang J, Lee DS. ; Investigators of the Registry of the Canadian Stroke Network. Reinitiation of anticoagulation after warfarin-associated intracranial hemorrhage and mortality risk: the Best Practice for Reinitiating Anticoagulation Therapy After Intracranial Bleeding (BRAIN) study. Can J Cardiol 2012; 28 (01) 33-39
  • 18 Kuramatsu JB, Gerner ST, Schellinger PD. , et al. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA 2015; 313 (08) 824-836
  • 19 Hawryluk GW, Austin JW, Furlan JC, Lee JB, O'Kelly C, Fehlings MG. Management of anticoagulation following central nervous system hemorrhage in patients with high thromboembolic risk. J Thromb Haemost 2010; 8 (07) 1500-1508
  • 20 Witt DM, Delate T, Hylek EM. , et al. Effect of warfarin on intracranial hemorrhage incidence and fatal outcomes. Thromb Res 2013; 132 (06) 770-775
  • 21 Pasquini M, Charidimou A, van Asch CJJ. , et al. Variation in restarting antithrombotic drugs at hospital discharge after intracerebral hemorrhage. Stroke 2014; 45 (09) 2643-2648
  • 22 Pennlert J, Asplund K, Carlberg B. , et al. Antithrombotic treatment following intracerebral hemorrhage in patients with and without atrial fibrillation. Stroke 2015; 46 (08) 2094-2099
  • 23 Becattini C, Sembolini A, Paciaroni M. Resuming anticoagulant therapy after intracerebral bleeding. Vascul Pharmacol 2016; 84: 15-24
  • 24 Fonville AF, Samarasekera N, Hutchison A, Perry D, Roos YB, Al-Shahi Salman R. Eligibility for randomized trials of treatments specifically for intracerebral hemorrhage: community-based study. Stroke 2013; 44 (10) 2729-2734
  • 25 Hansen BM, Ullman N, Norrving B, Hanley DF, Lindgren A. Applicability of clinical trials in an unselected cohort of patients with intracerebral hemorrhage. Stroke 2016; 47 (10) 2634-2637