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 & 54 others 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

Research output: Contribution to journalArticle

70 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2175-2182
Number of pages8
JournalStroke
Volume46
Issue number8
DOIs
StatePublished - Aug 30 2015

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Atrial Fibrillation
Stroke
Hemorrhage
Recurrence
Anticoagulants
Low Molecular Weight Heparin
Transient Ischemic Attack
National Institutes of Health (U.S.)
Outcome Assessment (Health Care)
Intracranial Embolism
Therapeutics
Secondary Prevention
Embolism
Multicenter Studies
Cohort Studies
Regression Analysis
Prospective Studies
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

Cite this

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

In: Stroke, Vol. 46, No. 8, 30.08.2015, p. 2175-2182.

Research output: Contribution to journalArticle

Paciaroni, M, Agnelli, G, Falocci, N, Caso, V, Becattini, C, Marcheselli, S, Rueckert, C, Pezzini, A, Poli, L, Padovani, A, Csiba, L, Szabó, L, Sohn, SI, Tassinari, T, Abdul-Rahim, AH, Michel, P, Cordier, M, Vanacker, P, Remillard, S, Alberti, A, Venti, M, Scoditti, U, Denti, L, Orlandi, G, Chiti, A, Gialdini, G, Bovi, P, Carletti, M, Rigatelli, A, Putaala, J, Tatlisumak, T, Masotti, L, Lorenzini, G, Tassi, R, Guideri, F, Martini, G, Tsivgoulis, G, Vadikolias, K, Liantinioti, C, Corea, F, Del Sette, M, Ageno, W, De Lodovici, ML, Bono, G, Baldi, A, D'Anna, S, Sacco, S, Carolei, A, Tiseo, C, Acciarresi, M, D'Amore, C, Imberti, D, Zabzuni, D, Doronin, B, Volodina, V, Consoli, D, Galati, F, Pieroni, A, Toni, D, Monaco, S, Baronello, MM, Barlinn, K, Pallesen, LP, Kepplinger, J, Bodechtel, U, Gerber, J, Deleu, D, Melikyan, G, Ibrahim, F, Akhtar, N, Mosconi, MG, Bubba, V, Silvestri, I & Lees, KR 2015, 'Early recurrence and cerebral bleeding in patients with acute ischemic stroke and atrial fibrillation: Effect of anticoagulation and its timing: The RAF study', Stroke, vol. 46, no. 8, pp. 2175-2182. https://doi.org/10.1161/STROKEAHA.115.008891
Paciaroni, Maurizio ; Agnelli, Giancarlo ; Falocci, Nicola ; Caso, Valeria ; Becattini, Cecilia ; Marcheselli, Simona ; Rueckert, Christina ; Pezzini, Alessandro ; Poli, Loris ; Padovani, Alessandro ; Csiba, Laszló ; Szabó, Lilla ; Sohn, Sung Il ; Tassinari, Tiziana ; Abdul-Rahim, Azmil H. ; Michel, Patrik ; Cordier, Maria ; Vanacker, Peter ; Remillard, Suzette ; Alberti, Andrea ; Venti, Michele ; Scoditti, Umberto ; Denti, Licia ; Orlandi, Giovanni ; Chiti, Alberto ; Gialdini, Gino ; Bovi, Paolo ; Carletti, Monica ; Rigatelli, Alberto ; Putaala, Jukka ; Tatlisumak, Turgut ; Masotti, Luca ; Lorenzini, Gianni ; Tassi, Rossana ; Guideri, Francesca ; Martini, Giuseppe ; Tsivgoulis, Georgios ; Vadikolias, Kostantinos ; Liantinioti, Chrissoula ; Corea, Francesco ; Del Sette, Massimo ; Ageno, Walter ; De Lodovici, Maria Luisa ; Bono, Giorgio ; Baldi, Antonio ; D'Anna, Sebastiano ; Sacco, Simona ; Carolei, Antonio ; Tiseo, Cindy ; Acciarresi, Monica ; D'Amore, Cataldo ; Imberti, Davide ; Zabzuni, Dorjan ; Doronin, Boris ; Volodina, Vera ; Consoli, Domenico ; Galati, Franco ; Pieroni, Alessio ; Toni, Danilo ; Monaco, Serena ; Baronello, Mario Maimone ; Barlinn, Kristian ; Pallesen, Lars Peder ; Kepplinger, Jessica ; Bodechtel, Ulf ; Gerber, Johannes ; Deleu, Dirk ; Melikyan, Gayane ; Ibrahim, Faisal ; Akhtar, Naveed ; Mosconi, Maria Giulia ; Bubba, Valentina ; Silvestri, Ilenia ; Lees, Kennedy R. / Early recurrence and cerebral bleeding in patients with acute ischemic stroke and atrial fibrillation : Effect of anticoagulation and its timing: The RAF study. In: Stroke. 2015 ; Vol. 46, No. 8. pp. 2175-2182.
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title = "Early recurrence and cerebral bleeding in patients with acute ischemic stroke and atrial fibrillation: Effect of anticoagulation and its timing: The RAF study",
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.",
author = "Maurizio Paciaroni and Giancarlo Agnelli and Nicola Falocci and Valeria Caso and Cecilia Becattini and Simona Marcheselli and Christina Rueckert and Alessandro Pezzini and Loris Poli and Alessandro Padovani and Laszl{\'o} Csiba and Lilla Szab{\'o} and Sohn, {Sung Il} and Tiziana Tassinari and Abdul-Rahim, {Azmil H.} and Patrik Michel and Maria Cordier and Peter Vanacker and Suzette Remillard and Andrea Alberti and Michele Venti and Umberto Scoditti and Licia Denti and Giovanni Orlandi and Alberto Chiti and Gino Gialdini and Paolo Bovi and Monica Carletti and Alberto Rigatelli and Jukka Putaala and Turgut Tatlisumak and Luca Masotti and Gianni Lorenzini and Rossana Tassi and Francesca Guideri and Giuseppe Martini and Georgios Tsivgoulis and Kostantinos Vadikolias and Chrissoula Liantinioti and Francesco Corea and {Del Sette}, Massimo and Walter Ageno and {De Lodovici}, {Maria Luisa} and Giorgio Bono and Antonio Baldi and Sebastiano D'Anna and Simona Sacco and Antonio Carolei and Cindy Tiseo and Monica Acciarresi and Cataldo D'Amore and Davide Imberti and Dorjan Zabzuni and Boris Doronin and Vera Volodina and Domenico Consoli and Franco Galati and Alessio Pieroni and Danilo Toni and Serena Monaco and Baronello, {Mario Maimone} and Kristian Barlinn and Pallesen, {Lars Peder} and Jessica Kepplinger and Ulf Bodechtel and Johannes Gerber and Dirk Deleu and Gayane Melikyan and Faisal Ibrahim and Naveed Akhtar and Mosconi, {Maria Giulia} and Valentina Bubba and Ilenia Silvestri and Lees, {Kennedy R.}",
year = "2015",
month = "8",
day = "30",
doi = "10.1161/STROKEAHA.115.008891",
language = "English (US)",
volume = "46",
pages = "2175--2182",
journal = "Stroke",
issn = "0039-2499",
publisher = "Lippincott Williams and Wilkins",
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TY - JOUR

T1 - Early recurrence and cerebral bleeding in patients with acute ischemic stroke and atrial fibrillation

T2 - Effect of anticoagulation and its timing: The RAF study

AU - Paciaroni, Maurizio

AU - Agnelli, Giancarlo

AU - Falocci, Nicola

AU - Caso, Valeria

AU - Becattini, Cecilia

AU - Marcheselli, Simona

AU - Rueckert, Christina

AU - Pezzini, Alessandro

AU - Poli, Loris

AU - Padovani, Alessandro

AU - Csiba, Laszló

AU - Szabó, Lilla

AU - Sohn, Sung Il

AU - Tassinari, Tiziana

AU - Abdul-Rahim, Azmil H.

AU - Michel, Patrik

AU - Cordier, Maria

AU - Vanacker, Peter

AU - Remillard, Suzette

AU - Alberti, Andrea

AU - Venti, Michele

AU - Scoditti, Umberto

AU - Denti, Licia

AU - Orlandi, Giovanni

AU - Chiti, Alberto

AU - Gialdini, Gino

AU - Bovi, Paolo

AU - Carletti, Monica

AU - Rigatelli, Alberto

AU - Putaala, Jukka

AU - Tatlisumak, Turgut

AU - Masotti, Luca

AU - Lorenzini, Gianni

AU - Tassi, Rossana

AU - Guideri, Francesca

AU - Martini, Giuseppe

AU - Tsivgoulis, Georgios

AU - Vadikolias, Kostantinos

AU - Liantinioti, Chrissoula

AU - Corea, Francesco

AU - Del Sette, Massimo

AU - Ageno, Walter

AU - De Lodovici, Maria Luisa

AU - Bono, Giorgio

AU - Baldi, Antonio

AU - D'Anna, Sebastiano

AU - Sacco, Simona

AU - Carolei, Antonio

AU - Tiseo, Cindy

AU - Acciarresi, Monica

AU - D'Amore, Cataldo

AU - Imberti, Davide

AU - Zabzuni, Dorjan

AU - Doronin, Boris

AU - Volodina, Vera

AU - Consoli, Domenico

AU - Galati, Franco

AU - Pieroni, Alessio

AU - Toni, Danilo

AU - Monaco, Serena

AU - Baronello, Mario Maimone

AU - Barlinn, Kristian

AU - Pallesen, Lars Peder

AU - Kepplinger, Jessica

AU - Bodechtel, Ulf

AU - Gerber, Johannes

AU - Deleu, Dirk

AU - Melikyan, Gayane

AU - Ibrahim, Faisal

AU - Akhtar, Naveed

AU - Mosconi, Maria Giulia

AU - Bubba, Valentina

AU - Silvestri, Ilenia

AU - Lees, Kennedy R.

PY - 2015/8/30

Y1 - 2015/8/30

N2 - 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.

AB - 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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U2 - 10.1161/STROKEAHA.115.008891

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EP - 2182

JO - Stroke

JF - Stroke

SN - 0039-2499

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