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JOURNAL ARTICLE
MULTICENTER STUDY

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: Effect of Anticoagulation and Its Timing: The RAF Study

Maurizio Paciaroni, Giancarlo Agnelli, Nicola Falocci, Valeria Caso, Cecilia Becattini, Simona Marcheselli, Christina Rueckert, Alessandro Pezzini, Loris Poli, Alessandro Padovani, Laszló Csiba, Lilla Szabó, Sung-Il Sohn, Tiziana Tassinari, Azmil H Abdul-Rahim, Patrik Michel, Maria Cordier, Peter Vanacker, Suzette Remillard, Andrea Alberti, Michele Venti, Umberto Scoditti, Licia Denti, Giovanni Orlandi, Alberto Chiti, Gino Gialdini, Paolo Bovi, Monica Carletti, Alberto Rigatelli, Jukka Putaala, Turgut Tatlisumak, Luca Masotti, Gianni Lorenzini, Rossana Tassi, Francesca Guideri, Giuseppe Martini, Georgios Tsivgoulis, Kostantinos Vadikolias, Chrissoula Liantinioti, Francesco Corea, Massimo Del Sette, Walter Ageno, Maria Luisa De Lodovici, Giorgio Bono, Antonio Baldi, Sebastiano D'Anna, Simona Sacco, Antonio Carolei, Cindy Tiseo, Monica Acciarresi, Cataldo D'Amore, Davide Imberti, Dorjan Zabzuni, Boris Doronin, Vera Volodina, Domenico Consoli, Franco Galati, Alessio Pieroni, Danilo Toni, Serena Monaco, Mario Maimone Baronello, Kristian Barlinn, Lars-Peder Pallesen, Jessica Kepplinger, Ulf Bodechtel, Johannes Gerber, Dirk Deleu, Gayane Melikyan, Faisal Ibrahim, Naveed Akhtar, Maria Giulia Mosconi, Valentina Bubba, Ilenia Silvestri, Kennedy R Lees
Stroke; a Journal of Cerebral Circulation 2015, 46 (8): 2175-82
26130094

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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