Apixaban versus no anticoagulation after anticoagulation-associated intracerebral haemorrhage in patients with atrial fibrillation in the Netherlands (APACHE-AF): a randomised, open-label, phase 2 trial
Year: 2021
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: In patients with atrial fibrillation who survive an anticoagulation-associated intracerebral haemorrhage, a decision must be made as to whether restarting or permanently avoiding anticoagulation is the best long-term strategy to prevent recurrent stroke and other vascular events. In APACHE-AF, we aimed to estimate the rates of non-fatal stroke or vascular death in such patients when treated with apixaban compared with when anticoagulation was avoided, to inform the design of a larger trial. METHODS: -VASc score of at least 2 and a score on the modified Rankin scale (mRS) of 4 or less. Participants were randomly assigned (1:1) to receive oral apixaban (5 mg twice daily or a reduced dose of 2·5 mg twice daily) or to avoid anticoagulation (oral antiplatelet agents could be prescribed at the discretion of the treating physician) by a central computerised randomisation system, stratified by the intention to start or withhold antiplatelet therapy in participants randomised to avoiding anticoagulation, and minimised for age and intracerebral haemorrhage location. The primary outcome was a composite of non-fatal stroke or vascular death, whichever came first, during a minimum follow-up of 6 months, analysed using Cox proportional hazards modelling in the intention-to-treat population. APACHE-AF is registered with ClinicalTrials.gov (NCT02565693) and the Netherlands Trial Register (NL4395), and the trial is closed to enrolment at all participating sites. FINDINGS: Between Jan 15, 2015, and July 6, 2020, we recruited 101 patients (median age 78 years [IQR 73-83]; 55 [54%] were men and 46 [46%] were women; 100 [99%] were White and one [1%] was Black) a median of 46 days (IQR 21-74) after intracerebral haemorrhage. 50 were assigned to apixaban and 51 to avoid anticoagulation (of whom 26 [51%] started antiplatelet therapy). None were lost to follow-up. Over a median follow-up of 1·9 years (IQR 1·0-3·1; 222 person-years), non-fatal stroke or vascular death occurred in 13 (26%) participants allocated to apixaban (annual event rate 12·6% [95% CI 6·7-21·5]) and in 12 (24%) allocated to avoid anticoagulation (11·9% [95% CI 6·2-20·8]; adjusted hazard ratio 1·05 [95% CI 0·48-2·31]; p=0·90). Serious adverse events that were not outcome events occurred in 29 (58%) of 50 participants assigned to apixaban and 29 (57%) of 51 assigned to avoid anticoagulation. INTERPRETATION: Patients with atrial fibrillation who had an intracerebral haemorrhage while taking anticoagulants have a high subsequent annual risk of non-fatal stroke or vascular death, whether allocated to apixaban or to avoid anticoagulation. Our data underline the need for randomised controlled trials large enough to allow identification of subgroups in whom restarting anticoagulation might be either beneficial or hazardous. FUNDING: Dutch Heart Foundation (grant 2012T077).
Source: The Lancet Neurology
Authors: Floris H B M Schreuder, Koen M van Nieuwenhuizen, Jeannette Hofmeijer, Sarah E Vermeer, Henk Kerkhoff, Elles Zock, Gert-Jan Luijckx, Gert P Messchendorp, Julia van Tuijl, H Paul Bienfait, Suzanne J Booij, Ido R van den Wijngaard, Michel J M Remmers, Antonia H C M L Schreuder, Diederik W Dippel, Julie Staals, Paul J A M Brouwers, Marieke J H Wermer, Jonathan M Coutinho, Vincent I H Kwa, Isabelle C van Gelder, Roger E G Schutgens, Berber Zweedijk, Ale Algra, Jan Willem van Dalen, L Jaap Kappelle, Gabriel J E Rinkel, H Bart van der Worp, Catharina J M Klijn
Institutions: Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, University Medical Center Utrecht, Rijnstate Hospital, Albert Schweitzer Ziekenhuis, University Medical Center Groningen, Elisabeth-TweeSteden Ziekenhuis, Gelre Hospitals, Canisius-Wilhelmina Ziekenhuis, Leiden University Medical Center, Medisch Centrum Haaglanden, Stichting Haaglanden Medisch Centrum, Amphia Ziekenhuis, Zuyderland Medisch Centrum, Erasmus MC, Maastricht University Medical Centre, Maastricht University, Medisch Spectrum Twente, Amsterdam UMC Location University of Amsterdam, Amsterdam University Medical Centers, OLVG, Utrecht University, Radboud University Nijmegen
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
Funder: ZonMw
Awards: G4156226487, G8785444225
OpenAlex ID: W3207839173