Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source.

Aged Antithrombins / administration & dosage Aspirin / administration & dosage Dabigatran / administration & dosage Double-Blind Method Female Hemorrhage / chemically induced Humans Incidence Intracranial Embolism / drug therapy Kaplan-Meier Estimate Male Middle Aged Platelet Aggregation Inhibitors / administration & dosage Recurrence Secondary Prevention Stroke / etiology

Journal

The New England journal of medicine

ISSN: 1533-4406

Titre abrégé: N Engl J Med

Pays: United States

ID NLM: 0255562

Informations de publication

Date de publication:
16 05 2019

Historique:

entrez: 16 5 2019

pubmed: 16 5 2019

medline: 29 5 2019

Statut: ppublish

Résumé

Cryptogenic strokes constitute 20 to 30% of ischemic strokes, and most cryptogenic strokes are considered to be embolic and of undetermined source. An earlier randomized trial showed that rivaroxaban is no more effective than aspirin in preventing recurrent stroke after a presumed embolic stroke from an undetermined source. Whether dabigatran would be effective in preventing recurrent strokes after this type of stroke was unclear. We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding. A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P = 0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively. In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group. (Funded by Boehringer Ingelheim; RE-SPECT ESUS ClinicalTrials.gov number, NCT02239120.).

Sections du résumé

BACKGROUND

METHODS

We conducted a multicenter, randomized, double-blind trial of dabigatran at a dose of 150 mg or 110 mg twice daily as compared with aspirin at a dose of 100 mg once daily in patients who had had an embolic stroke of undetermined source. The primary outcome was recurrent stroke. The primary safety outcome was major bleeding.

RESULTS

A total of 5390 patients were enrolled at 564 sites and were randomly assigned to receive dabigatran (2695 patients) or aspirin (2695 patients). During a median follow-up of 19 months, recurrent strokes occurred in 177 patients (6.6%) in the dabigatran group (4.1% per year) and in 207 patients (7.7%) in the aspirin group (4.8% per year) (hazard ratio, 0.85; 95% confidence interval [CI], 0.69 to 1.03; P = 0.10). Ischemic strokes occurred in 172 patients (4.0% per year) and 203 patients (4.7% per year), respectively (hazard ratio, 0.84; 95% CI, 0.68 to 1.03). Major bleeding occurred in 77 patients (1.7% per year) in the dabigatran group and in 64 patients (1.4% per year) in the aspirin group (hazard ratio, 1.19; 95% CI, 0.85 to 1.66). Clinically relevant nonmajor bleeding occurred in 70 patients (1.6% per year) and 41 patients (0.9% per year), respectively.

CONCLUSIONS

In patients with a recent history of embolic stroke of undetermined source, dabigatran was not superior to aspirin in preventing recurrent stroke. The incidence of major bleeding was not greater in the dabigatran group than in the aspirin group, but there were more clinically relevant nonmajor bleeding events in the dabigatran group. (Funded by Boehringer Ingelheim; RE-SPECT ESUS ClinicalTrials.gov number, NCT02239120.).

Identifiants

DOI: 10.1056/NEJMoa1813959 PMID: 31091372

pubmed: 31091372

doi: 10.1056/NEJMoa1813959

doi:

Substances chimiques

Antithrombins 0

Platelet Aggregation Inhibitors 0

Dabigatran I0VM4M70GC

Aspirin R16CO5Y76E

Banques de données

ClinicalTrials.gov

['NCT02239120']

Types de publication

Comparative Study Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1906-1917

Investigateurs

Hans-Christoph Diener (HC)

Ralph Sacco (R)

J Donald Easton (JD)

Christopher Granger (C)

Lisa Cronin (L)

Claudia Grauer (C)

Daniel Cotton (D)

Shinichiro Uchiyama (S)

Richard Bernstein (R)

Conrado Estol (C)

Cecilia Bahit (C)

Geoff Donnan (G)

Michael Brainin (M)

Robin Lemmens (R)

Sheila Martins (S)

Frank Silver (F)

Sergio Illanes (S)

Yongjun Wang (Y)

Mario Munoz (M)

Zdravka Poljakovic (Z)

Daniel Sanak (D)

Janika Korv (J)

Didier Leys (D)

Martin Grond (M)

Georgios K Tsivgoulis (GK)

Lawrence Ka Sing Wong (LKS)

Laszlo Csiba (L)

M V Padma Srivastava (MVP)

Natan Bornstein (N)

Danilo Toni (D)

Kazunori Toyoda (K)

Byung-Chul Lee (BC)

Hamidon Bin Basri (HB)

Jorge Villareal-Careaga (J)

Danny Moises Barrientos Iman (DM)

Segundo Carlos Abanto Argomedo (SC)

Adam Stepien (A)

José Ferro (J)

Miroslav Odinak (M)

Ljiljana Beslac-Bumbasirevic (L)

Hui Meng Chang (HM)

Zuzana Gdovinova (Z)

Bojana Zvan (B)

Christo Coetzee (C)

Jaime Masjuan (J)

Christina Sjostrand (C)

Phillippe Lyrer (P)

Chia-Wei Liou (CW)

Nijasri Charnnarong Suwanwela (NC)

Nevzat Uzuner (N)

Tamara Mishchenko (T)

Jeffrey Saver (J)

Robert Makuch (R)

Kennedy Lees (K)

Paulus Kirchhof (P)

Ruediger Von Kummer (R)

Jan G P Tijssen (JGP)

Frank Schuetz (F)

Heinrich Mattle (H)

Waimei Amy Tai (WA)

Valeria Caso (V)

Louis Caplan (L)

James Januzzi (J)

Kenneth Mahaffey (K)

Alan Miller (A)

Renato Lopes (R)

Maria Cristina Zurru (MC)

Francisco Klein (F)

Alberto Caccavo (A)

Alberto Lorenzatti (A)

Pablo Ioli (P)

Chris Bladin (C)

Martin Krause (M)

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Rohan Grimley (R)

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Stephen Davis (S)

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Candice Delcourt (C)

Andrew Wong (A)

Jonathon Sturm (J)

Geoffrey Cloud (G)

Romesh Markus (R)

Vincent Thijs (V)

Christian Eggers (C)

Gerhard Daniel (G)

Hans-Peter Haring (HP)

Michael Knoflach (M)

Nilguen Yilmaz-Kaymaz (N)

Milan Vosko (M)

Kurt Niederkorn (K)

Christoph Baumgartner (C)

Frederik Vanhee (F)

Andre Peeters (A)

Georges Mairesse (G)

Philippe Desfontaines (P)

Patrice Laloux (P)

Dimitri Hemelsoet (D)

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Marie-Christine Hasenbroekx (MC)

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