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AF Registry

Berlin Cohort Study on Oral Anticoagulation in Patients with Atrial Fibrillation and Acute Ischemic Stroke

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Scientific background

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia and the number of patients with AF will increase within the next years as the population ages. Different forms of AF (i.e. paroxysmal, persistent and permanent) confer a similar stroke risk and furthermore AF accounts for every fifth ischemic stroke in Germany. Patients with AF-related cardio-embolic strokes show a poorer prognosis and a higher recurrence rate compared to strokes of other etiologies. Long-term oral anticoagulation with vitamin K antagonists (VKAs) reduces the risk of recurrent stroke in AF patients by about two thirds compared to placebo and is substantially more effective than acetylsalicylic acid. It emerges that new oral anticoagulants (NOACs) such as dabigatran, rivaroxaban or apixaban are at least as effective or even more effective compared to the VKA warfarin for the prevention of recurrent stroke, (intracranial) bleeding and death. National and international guidelines recommend oral anticoagulation for patients with AF and prior ischemic stroke with the highest level of evidence.

The detection of paroxysmal, so far undetected ("silent") AF represents a major diagnostic challenge in patients with acute ischemic stroke, remaining undetected in a relevant proportion of stroke patients. However, prolonged (post-hospital) ECG monitoring and systematic analysis of ECG recordings enhances detection of non-permanent AF after ischemic stroke, but optimal length of monitoring remains unclear. Moreover, implantable cardiac-event recorders increase AF detection rates in selected stroke cohorts, but are invasive and expensive, not supporting routine use. As most of the published ECG data are taken from single-center studies, current stroke guidelines do not recommend prolonged ECG monitoring and do not specify the requirements for ECG analysis in stroke survivors. Subsequently, there is no common practice or "gold standard" of ECG monitoring in most healthcare systems, as well as in the German stroke unit system. This fact likely results in an important under-diagnosis of AF in stroke survivors. A systematic assessment and randomized comparison of the diagnostic yield and therapeutic impact of prolonged ECG monitoring for silent AF in stroke survivors would have immediate impact on patient management, as oral anticoagulation would only be prescribed to optimize secondary stroke prevention after ischemic stroke or TIA when AF has been documented. Moreover, a standardized prolonged continuous ECG monitoring will help to clarify the clinical relevance of short-lasting atrial runs (<30 s and ≥ 6 conducted premature activations; so called "paroxysmal short atrial tachycardia"), a common finding in stroke patients. According to US claims data, paroxysmal short atrial tachycardia was independently associated with a twofold higher risk of subsequent stroke. In addition, the Copenhagen Holter Study demonstrated that excessive supraventricular ectopic activity was associated with an almost threefold risk of hospital admission due to AF or ischemic stroke. Nevertheless, paroxysmal short atrial tachycardia as well as excessive supraventricular ectopic activity is not defined as (paroxysmal) AF and therefore, there is no indication for the prescription of oral anticoagulants according to guidelines. Taken together, well-designed large prospective, randomized, multicenter studies are urgently needed to clarify these major issues of stroke prevention and will help to optimize the use of VKAs and NOACs. The proposed MonDAFIS study will help to define the optimal duration and modality of ECG recording after ischemic stroke or TIA and could change the diagnostic workup for stroke patients in Germany and throughout Europe.

Study design

Investigator-initiated, prospective, randomized, open-label, multi-center trial with two parallel groups. Patients were randomized 1:1 into a standard care group and a standard care plus additional Holter ECG monitoring group, respectively. More information at here.

Biometric core lab

Power calculation and statistical analysis is conducted under supervision of Prof. P. U. Heuschmann, MD, at the Institute for Clinical Epidemiology and Biometry at the University of Würzburg.

Collaborating research facilities

Implementation of the study was realized in collaboration with 14 study sites encompassing all certified stroke units of Berlin metropolitan area. The initiation phase of the study was completed in June 2015. In this regard, we give thanks to all collaborating clinical study sites for the professional and sincere working climate during the initiation procedure.

Recruitment

After starting the recruitment initiation at Charité – Universitätsmedizin Berlin in December 2014 and in April 2015 at additional recruiting study sites, 3,470 participants were included. The study could be completed on schedule.
Sincere thanks to all recruiting study sites for their dedicating work.

Follow-up

A follow-up survey of the study patients is planned over a period of three years.

Monitoring

The subject matter of monitoring is the control of adherence to the study protocol according to GCP as well as compliance with legal regularities. Furthermore monitoring ensures a high standard of data quality and consequently raises the validity of the study.

Publications

Trial design paper

Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke (MonDAFIS): Rationale and design of a prospective randomized multicenter study.
Haeusler KG, Kirchhof P, Heuschmann PU, Laufs U, Busse O, Kunze C, Thomalla G, Nabavi DG, Röther J, Veltkamp R, Endres M.
Am Heart J. 2016 Feb;172:19-25. doi: 10.1016/j.ahj.2015.10.010. Epub 2015 Oct 21.
PMID: 26856211.
 

Baseline paper (I)

Oral anticoagulation in patients with atrial fibrillation and acute ischaemic stroke: design and baseline data of the prospective multicentre Berlin Atrial Fibrillation Registry.
Haeusler KG, Tütüncü S, Kunze C, Schurig J, Malsch C, Harder J, Wiedmann S, Dimitrijeski B, Ebinger M, Hagemann G, Hamilton F, Honermann M, Jungehulsing GJ, Kauert A, Koennecke HC, Leithner C, Mackert BM, Masuhr F, Nabavi D, Rocco A, Schmehl I, Schmitz B, Sparenberg P, Stingele R, von Brevern M, Völzke E, Dietzel J, Heuschmann PU, Endres M.
Europace. 2019 Nov 1;21(11):1621-1632. doi: 10.1093/europace/euz199.
PMID: 31397475.

Related projects

MonDAFIS – Impact of standardized MONitoring for Detection of Atrial Fibrillation in Ischemic Stroke

Investigator-initiated, prospective, randomized, open-label, multi-center trial with two parallel groups. Randomization of patients happened 1:1 into one group that received standard care and one group that received standard care plus additional Holter ECG monitoring.
More information/project description

Team of the Study Headquarters

Prof. Matthias Endres, MD

Director Dept. of Neurology and Dept. of Experimental Neurology (ex officio), Head of Reseach Group Endres (Interdisciplinary Stroke Research)

Prof. Matthias Endres, MD

Former members

  • Prof. Karl Georg Häusler, MD
    Principal Investigator
     
  • Claudia Kunze, BA
    Project Manager
     
  • Petra Dem
    Data Manager
     
  • Larissa Pfeiler
    Research Assistant
     
  • Michael Krämer
    IT


"Berlin register of medicinal treatment after cerebral ischaemia in patients with known atrial fibrillation", previously headed by Prof. Karl Georg Häusler, MD, and now, since the former’s replacement at the University Hospital of Würzburg, by Prof. Matthias Endres, MD, is a prospective observational study by the Charité – Universitätsmedizin Berlin, conducted by the study centre at the Centre for Stroke Research Berlin (CSB) and financially supported by Bayer HealthCare, Bayer Vital GmbH.