Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation

Maurizio Paciaroni(Fondazione Humanitas per la Ricerca), Giancarlo Agnelli(Fondazione Humanitas per la Ricerca), Nicola Falocci(Fondazione Humanitas per la Ricerca), Valeria Caso(Fondazione Humanitas per la Ricerca), Cecilia Becattini(Fondazione Humanitas per la Ricerca), Simona Marcheselli(Fondazione Humanitas per la Ricerca), Christina Rueckert(Fondazione Humanitas per la Ricerca), Alessandro Pezzini(Fondazione Humanitas per la Ricerca), Loris Poli(Fondazione Humanitas per la Ricerca), Alessandro Padovani(Fondazione Humanitas per la Ricerca), László Csiba(Fondazione Humanitas per la Ricerca), Lilla Szabó(Fondazione Humanitas per la Ricerca), Sung‐Il Sohn(Fondazione Humanitas per la Ricerca), Tiziana Tassinari(Fondazione Humanitas per la Ricerca), Azmil H. Abdul‐Rahim(Fondazione Humanitas per la Ricerca), Patrik Michel(Fondazione Humanitas per la Ricerca), Maria Cordier(Fondazione Humanitas per la Ricerca), Peter Vanacker(Fondazione Humanitas per la Ricerca), Suzette Rémillard(Fondazione Humanitas per la Ricerca), Andrea Alberti(Fondazione Humanitas per la Ricerca), Michele Venti(Fondazione Humanitas per la Ricerca), Umberto Scoditti(Fondazione Humanitas per la Ricerca), Licia Denti(Fondazione Humanitas per la Ricerca), Giovanni Orlandi(Fondazione Humanitas per la Ricerca), Alberto Chiti(Fondazione Humanitas per la Ricerca), Gino Gialdini(Fondazione Humanitas per la Ricerca), Paolo Bovi(Fondazione Humanitas per la Ricerca), Monica Carletti(Fondazione Humanitas per la Ricerca), Alberto Rigatelli(Fondazione Humanitas per la Ricerca), Jukka Putaala(Fondazione Humanitas per la Ricerca), Turgut Tatlisumak(Fondazione Humanitas per la Ricerca), Luca Masotti(Fondazione Humanitas per la Ricerca), Gianni Lorenzini(Fondazione Humanitas per la Ricerca), Rossana Tassi(Fondazione Humanitas per la Ricerca), Francesca Guideri(Fondazione Humanitas per la Ricerca), Giuseppe Martini(Fondazione Humanitas per la Ricerca), Georgios Tsivgoulis(National and Kapodistrian University of Athens), Kostantinos Vadikolias(Fondazione Humanitas per la Ricerca), Chrissoula Liantinioti(Fondazione Humanitas per la Ricerca), Francesco Corea(Fondazione Humanitas per la Ricerca), Massimo Del Sette(Fondazione Humanitas per la Ricerca), Walter Ageno(Fondazione Humanitas per la Ricerca), Maria Luisa De Lodovici(Fondazione Humanitas per la Ricerca), Giorgio Bono(Fondazione Humanitas per la Ricerca), Antonio Baldi(Fondazione Humanitas per la Ricerca), Sebastiano D’Anna(Fondazione Humanitas per la Ricerca), Simona Sacco(Fondazione Humanitas per la Ricerca), Antonio Carolei(Fondazione Humanitas per la Ricerca), Cindy Tiseo(Fondazione Humanitas per la Ricerca), Monica Acciarresi(Fondazione Humanitas per la Ricerca), Cataldo D’Amore(Fondazione Humanitas per la Ricerca), Davide Imberti(Fondazione Humanitas per la Ricerca), Dorjan Zabzuni(Fondazione Humanitas per la Ricerca), Б. М. Доронин(Fondazione Humanitas per la Ricerca), Vera Volodina(Fondazione Humanitas per la Ricerca), Domenico Consoli(Fondazione Humanitas per la Ricerca), Franco Galati(Fondazione Humanitas per la Ricerca), Alessio Pieroni(Fondazione Humanitas per la Ricerca), Danilo Toni(Fondazione Humanitas per la Ricerca), Serena Monaco(Fondazione Humanitas per la Ricerca), Mario Maimone Baronello(Fondazione Humanitas per la Ricerca), Kristian Barlinn(Fondazione Humanitas per la Ricerca), Lars‐Peder Pallesen(Fondazione Humanitas per la Ricerca), Jessica Kepplinger(Fondazione Humanitas per la Ricerca), Ulf Bodechtel(Fondazione Humanitas per la Ricerca), Johannes Gerber(Fondazione Humanitas per la Ricerca), Dirk Deleu(Fondazione Humanitas per la Ricerca), Gayane Melikyan(Fondazione Humanitas per la Ricerca), Faisal Ibrahim(Fondazione Humanitas per la Ricerca), Naveed Akhtar(Fondazione Humanitas per la Ricerca), Maria Giulia Mosconi(Fondazione Humanitas per la Ricerca), Valentina Bubba(Fondazione Humanitas per la Ricerca), Ilenia Silvestri(Fondazione Humanitas per la Ricerca), Kennedy R. Lees(Fondazione Humanitas per la Ricerca)
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Abstract

BACKGROUND AND PURPOSE: The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. METHODS: The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. RESULTS: Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). CONCLUSIONS: Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.


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