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Observational Study
. 2017 Nov 29;6(12):e007034.
doi: 10.1161/JAHA.117.007034.

Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study

Maurizio Paciaroni  1 , Giancarlo Agnelli  2 , Nicola Falocci  2 , Georgios Tsivgoulis  3 , Kostantinos Vadikolias  4 , Chrysoula Liantinioti  3 , Maria Chondrogianni  3 , Paolo Bovi  5 , Monica Carletti  5 , Manuel Cappellari  5 , Marialuisa Zedde  6 , George Ntaios  7 , Efstathia Karagkiozi  7 , George Athanasakis  7 , Kostantinos Makaritsis  7 , Giorgio Silvestrelli  8 , Alessia Lanari  8 , Alfonso Ciccone  8 , Jukka Putaala  9 , Liisa Tomppo  9 , Turgut Tatlisumak  9   10   11 , Azmil H Abdul-Rahim  12 , Kennedy R Lees  12 , Andrea Alberti  2 , Michele Venti  2 , Monica Acciarresi  2 , Cataldo D'Amore  2 , Cecilia Becattini  2 , Maria Giulia Mosconi  2 , Ludovica Anna Cimini  2 , Rossana Soloperto  2 , Luca Masotti  13 , Vieri Vannucchi  13 , Gianni Lorenzini  14 , Rossana Tassi  14 , Francesca Guideri  14 , Maurizio Acampa  14 , Giuseppe Martini  14 , Sung-Il Sohn  15 , Simona Marcheselli  16 , Nicola Mumoli  17 , Maria Luisa De Lodovici  18 , Giorgio Bono  18 , Karen L Furie  19 , Prasanna Tadi  19 , Shadi Yaghi  19 , Danilo Toni  20 , Federica Letteri  20 , Tiziana Tassinari  21 , Odysseas Kargiotis  22 , Enrico Maria Lotti  23 , Yuriy Flomin  24 , Michelangelo Mancuso  25 , Miriam Maccarrone  25 , Nicola Giannini  25 , Fabio Bandini  26 , Alessandro Pezzini  27 , Loris Poli  27 , Alessandro Padovani  27 , Umberto Scoditti  28 , Licia Denti  29 , Domenico Consoli  30 , Franco Galati  30 , Simona Sacco  31 , Antonio Carolei  31 , Cindy Tiseo  31 , Vanessa Gourbali  32 , Giovanni Orlandi  33 , Martina Giuntini  33 , Alberto Chiti  34 , Elisa Giorli  34 , Gino Gialdini  34 , Francesco Corea  35 , Walter Ageno  36 , Marta Bellesini  36 , Giovanna Colombo  36 , Serena Monaco  37 , Mario Maimone Baronello  37 , Theodore Karapanayiotides  38 , Valeria Caso  2
Affiliations
Observational Study

Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study

Maurizio Paciaroni et al. J Am Heart Assoc. .

Abstract

Background: The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and their timing in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention.

Methods and results: Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA2DS2-VASc score >4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated >14 days after acute stroke.

Conclusions: In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.

Keywords: acute stroke; anticoagulants; atrial fibrillation; secondary prevention.

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Figures

Figure 1
Figure 1
Cumulative probability of a first outcome event within 90 days from the index stroke.
Figure 2
Figure 2
Combined risks of outcome events (ischemic and hemorrhagic) depending on the time between onset and initiation of therapy with non–vitamin K oral anticoagulants (NOACs). The lower risk of the combined outcome event was within 14 days.
Figure 3
Figure 3
Risks of outcome events depending on the time between onset and initiation of therapy with non–vitamin K oral anticoagulants (NOACs).
Figure 4
Figure 4
Cumulative risks of the combined end point (ischemic and hemorrhagic) for individual non–vitamin K oral anticoagulants.
Figure 5
Figure 5
Cumulative risks of the ischemic or hemorrhagic end point for the non–vitamin K oral anticoagulants.
Figure 6
Figure 6
Time of initiating therapy for non–vitamin K oral anticoagulants.
Figure 7
Figure 7
Cumulative risks of patients treated with low‐molecular‐weight heparin (LMWH) before non–vitamin K oral anticoagulants (NOACs) vs patients treated with NOACs alone.
Figure 8
Figure 8
Cumulative risks of ischemic or hemorrhagic outcome events in patients with small vs medium/large lesions.
See this image and copyright information in PMC

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