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Medical Treatment of Stroke

AFFILIATED PROFESSOR OF NEUROLOGY WITH SPECIAL FOCUS ON MEDICAL TREATMENT OF STROKE AT THE DEPARTMENT OF CLINICAL MEDICINE, FACULTY OF HEALTH AND MEDICAL SCIENCES, UNIVERSITY OF COPENHAGEN

OVERVIEW

PROJECTS

Outcome of intracerebral haemorrhage in patients pre-treated with anticoagulants – a Danish nationwide analysis. Based on a nationwide sample of stroke patients, this study aims to describe one-year survival after ICH in Patients pre-treated with any non-vitamin-K-antagonist in comparison to patient pre-treated with vitamin-k-antagonists.

Characteristics and outcome of intracerebral haemorrhage in patients pre-treated with vitamin-K antagonists and non-vitamin-K antagonists - The Capital Region  Anticoagulation-associated ICH study – the COOL-ICH study. Based on all patients hospitalized in the capital region of Denmark with ICH pre-treated with non-vitamin-K-antagonist we plan to describe patient’s characteristic, clinical and radiological findings of the incident as well as course, interventions and outcome and compare findings to patients with ICH pre-treated with vitamin-K-antagonist

MembersThorsten Steiner*#, Hanne Christensen**, Christian Ovenson**, Jan Purrucker#, Roland Veltkamp*##
*Department of Neurology, Klinikum Frankfurt Höchst; Germany; **Department of Neurology Bispebjerg Hospital, University of Copenhagen, Denmark #Department of Neurology, Heidelberg University Hospital, Germany##;Imperial College, London, United Kingdom

CLINICAL STUDIES

Clinical Studies on intracerebral hemorrhage, and use of reversal agent in patients with ICH related to antithrombotic therapies

The Fresh frozen plasma (FFP) versus prothrombin complex concentrate (PCC) in patients with intracranial haemorrhage related to vitamin K antagonists (INCH) trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded-endpoint trial (PROBE). Prof. Steiner is the principal investigator of the trial. The study was published in Lancet Neurology and demonstrated that PCC normalized the INR significantly faster than FFP, and prevented hematoma expansion significantly more than FFP at 3 and 24 hours.1 Currently the group is working on a meta-analysis on RCTs that studied efficacy of FFP vs. PCC in situations of life-threatening bleeding or in need for urgent procedures.

Reversal of dabigatran anticoagulant effect with idarucizumab (REVERSE-AD) is global multi-centre prospective case-series to evaluate the reversal of the anticoagulant effects of dabigatran by the specific reversal agent „idarucizumab“ in patients treated with dabigatran and who have uncontrolled bleeding or require emergency surgery or procedures. Prof. Steiner is member oft he DSMB (data safety and monitoring board). Study results on the first 90 patients were published in the NEJM in 2015.2 Results revealed that idarucizumab normalized ecarin clotting time and diluted thrombin time, and was safe and not associated with any major side effects. The study aimed for 500 patients. Preliminary results of these patients were published during the AHA meeting in November 2016.3 An invited review on the use of reversal agents in patients with ICH related to oral anticoagulants is currently in print.4 The analysis of final results form REVERSE is currently under way.

The second Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage (ATACH-2) is a global, multicentre RCT trial that compared the efficacy of intensive (<140 mmHg) and standard (<180 mmHg) systolic blood pressure lowering to improve clinical outcome in patients with acute intracerebral haemorrhage. Prof. Steiner is the German / European coordinator of the study. The study was prematurely stopped because of futility after a prespecified interim analysis. Study results were published in the NEJM.5

Other clinical studies

Vojta therapy in early stroke rehabilitations
This is a randomized controlled single centre pilot study to compare Vojta and conventional physiotherapy in patients with acute ischemic (AIS) or hemorrhagic stroke, (NCT03035968)6 Prof. Steiner is supervisor and sub-investigator of the study. Principal investigator: Corinna Epple (Department of Neurology, Klinikum Frankfurt Höchst, Germany)

COLLABORATIONS

Registry of Acute Stroke Under Novel Oral Anticoagulants - PRIME  (RASUNOA-PRIME). Prospective registry run by Prof. Veltkamp.

EDITORIAL WORK

Prof. Steiner is associated editor of the International Journal of Stroke (IJS), editor of the CME-section of Der Nervenarzt, and member of the editorial board of Stroke, and European Stroke Journal.

SCIENTIFIC SOCIETIES

Prof. Steiner is chairman of the Guidelines Committee of the European Stroke Organization (ESO, eso-stroke.org/eso-committees). He is senior author of the first standard operating procedure on guideline preparation of ESO,7 and co-chair of the ESO-Karolinska-Stroke Update conference that took place in November 2016 and lead to the publication of new ESO-recommendations on stroke. 8 Prof. Steiner is also a member of the Board of Directors of ESO.

REFERENCES

  1. Steiner T, Poli S, Griebe M, Husing J, Hajda J, Freiberger A, Bendszus M, Bosel J, Christensen H, Dohmen C, Hennerici M, Kollmer J, Stetefeld H, Wartenberg KE, Weimar C, Hacke W, Veltkamp R. Fresh frozen plasma versus prothrombin complex concentrate in patients with intracranial haemorrhage related to vitamin K antagonists (INCH): a randomised trial. Lancet Neurology 2016;15:566–573
  2. Pollack CV, Jr., Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kamphuisen PW, Kreuzer J, Levy JH, Sellke FW, Stangier J, Steiner T, Wang B, Kam CW, Weitz JI. Idarucizumab for dabigatran reversal. New England Journal of Medicine 2015;9:511-520
  3. Pollack CV, Jr., Reilly PA, Eikelboom J, Glund S, Verhamme P, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kamphuisen PW, Kreuzer J, Levy JH, Sellke FW, Stangier J, Steiner T, Wang B, Kam CW, Weitz JI. American Heart Association. Abstract: Updated results of the RE-VERSE AD study: Idarucizumab for dabigatran reversal in patients with serious bleeding or requiring urgent surgery or interventions. https://professional.heart.org/professional/EducationMeetings/MeetingsLiveCME/ScientificSessions/UCM_489715_Science-News---SS16-Clinical-Science-Special-Reports.jsp; 2016
  4. Steiner T, Weitz JI, Veltkamp R. Anticoagulant associated intracranial hemorrhage in the era of reversal agents. Stroke 2017;in print
  5. Qureshi AI, Palesch YY, Barsan WG, Hanley DF, Hsu CY, Martin RL, Moy CS, Silbergleit R, Steiner T, Suarez JI, Toyoda K, Wang Y, Yamamoto H, Yoon BW, Investigators A-T, the Neurological Emergency Treatment Trials N. Intensive Blood-Pressure Lowering in Patients with Acute Cerebral Hemorrhage. N Engl J Med 2016;375:1033-1043
  6. Epple C, Steiner T. Vojta Therapy in Early Stroke Rehabilitation (NCT03035968). https://clinicaltrials.gov/ct2/show/NCT03035968; 2017
  7. Ntaios G, Bornstein NM, Caso V, Christensen H, De Keyser J, Diener HC, Diez-Tejedor E, Ferro JM, Ford GA, Grau A, Keller E, Leys D, Russell D, Toni D, Turc G, Van der Worp B, Wahlgren N, Steiner T, European Stroke O. The European Stroke Organisation Guidelines: a standard operating procedure. Int J Stroke 2015;10 Suppl A100:128-135
  8. Ahmed N, Steiner T, Caso V, Wahlgren N. Recommendations from the ESO-Karolinska Stroke Update - Conference, Stockholm 13–15 November 2016. Eur Stroke J 2017