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Veltkamp, R, Korompoki, E, Harvey, KH, Harvey, ER, Fießler, C, Malzahn, U, Rücker, V, Montaner, J, Caso, V, Sibon, I, Ringleb, P, Halse, O, Hügen, K, Ullmann, S, Schuhmann, C, Todd, GP, Haas, K, Palà, E, Debette, S, Lachaize, M , D'Aoust, T, Enzinger, C, Ropele, S, Fandler-Höfler, S, Haidegger, M, Wang, Y, Wafa, HA, Cancelloni, V, Mosconi, MG, Lip, GYH, Lane, DA, Haefeli, WE, Foerster, KI, Wurmbach, VS, Nielsen, PB, Hajjar, K, Müller, P, Poli, S, Purrucker, J, Laible, M, D'Anna, L, Silva, Y, de Torres Chacon, R, Martínez-Sánchez, P, Boulanger, M, Norrving, B, Paré, G, Wachter, R, Ntaios, G, Wolfe, CDA, Heuschmann, PU, PRESTIGE-AF Consortium, and Lotto, R (2025) Direct oral anticoagulants versus no anticoagulation for the prevention of stroke in survivors of intracerebral haemorrhage with atrial fibrillation (PRESTIGE-AF): a multicentre, open-label, randomised, phase 3 trial. The Lancet, 405 (10482). pp. 927-936. ISSN 0140-6736
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Abstract
Background Direct oral anticoagulants (DOACs) reduce the rate of thromboembolism in patients with atrial fibrillation but the benefits and risks in survivors of intracerebral haemorrhage are uncertain. We aimed to determine whether DOACs reduce the risk of ischaemic stroke without substantially increasing the risk of recurrent intracerebral haemorrhage. Methods PRESTIGE-AF is a multicentre, open-label, randomised, phase 3 trial conducted at 75 hospitals in six European countries. Eligible patients were aged 18 years or older with spontaneous intracerebral haemorrhage, atrial fibrillation, an indication for anticoagulation, and a score of 4 or less on the modified Rankin Scale. Patients were randomly assigned (1:1) to a DOAC or no anticoagulation, stratified by intracerebral haemorrhage location and sex. Only the events adjudication committee was masked to treatment allocation. The coprimary endpoints were first ischaemic stroke and first recurrent intracerebral haemorrhage. Hierarchical testing for superiority and non-inferiority, respectively, was performed in the intention-to-treat population. The margin to establish non-inferiority regarding intracerebral haemorrhage was less than 1·735. The safety analysis was done in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT03996772, and is complete. Findings Between May 31, 2019, and Nov 30, 2023, 319 participants were enrolled and 158 were randomly assigned to the DOAC group and 161 to the no anticoagulant group. Patients' median age was 79 years (IQR 73–83). 113 (35%) of 319 patients were female and 206 (65%) were male. Median follow-up was 1·4 years (IQR 0·7–2·3). First ischaemic stroke occurred less frequently in the DOAC group than in the no anticoagulant group (hazard ratio [HR] 0·05 [95% CI 0·01–0·36]; log-rank p<0·0001). The rate of all ischaemic stroke events was 0·83 (95% CI 0·14–2·57) per 100 patient-years in the DOAC group versus 8·60 (5·43–12·80) per 100 patient-years in the no anticoagulant group. For first recurrent intracerebral haemorrhage, the DOAC group did not meet the prespecified HR for the non-inferiority margin of less than 1·735 (HR 10·89 [90% CI 1·95–60·72]; p=0·96). The event rate of all intracerebral haemorrhage was 5·00 (95% CI 2·68–8·39) per 100 patient-years in the DOAC group versus 0·82 (0·14–2·53) per 100 patient years in the no anticoagulant group. Serious adverse events occurred in 70 (44%) of 158 patients in the DOAC group and 89 (55%) of 161 patients in the no anticoagulant group. 16 (10%) patients in the DOAC group and 21 (13%) patients in the no anticoagulant group died. Interpretation DOACs effectively prevent ischaemic strokes in survivors of intracerebral haemorrhage with atrial fibrillation but a part of this benefit is offset by a substantially increased risk of recurrent intracerebral haemorrhage. To optimise stroke prevention in these vulnerable patients, further evidence from ongoing trials and a meta-analysis of randomised data is needed, as well as the evaluation of safer medical or mechanical alternatives for selected patients.
| Item Type: | Article |
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| Uncontrolled Keywords: | PRESTIGE-AF Consortium; Humans; Male; Female; Aged; Atrial Fibrillation; Cerebral Hemorrhage; Factor Xa Inhibitors; Stroke; Administration, Oral; Anticoagulants; Aged, 80 and over; Middle Aged; Ischemic Stroke; Recurrence; Pyrazoles; Pyridones; 32 Biomedical and Clinical Sciences; 3202 Clinical Sciences; Hematology; Stroke; Prevention; Clinical Research; Brain Disorders; Cerebrovascular; Clinical Trials and Supportive Activities; Cardiovascular; Patient Safety; 6.1 Pharmaceuticals; Cardiovascular; Stroke; 11 Medical and Health Sciences; General & Internal Medicine; 32 Biomedical and clinical sciences; 42 Health sciences |
| Subjects: | R Medicine > RT Nursing |
| Divisions: | Nursing and Advanced Practice |
| Publisher: | Elsevier |
| SWORD Depositor: | A Symplectic |
| Date Deposited: | 21 Mar 2025 16:12 |
| Last Modified: | 21 Mar 2025 16:15 |
| DOI or ID number: | 10.1016/s0140-6736(25)00333-2 |
| URI: | https://researchonline.ljmu.ac.uk/id/eprint/25957 |
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