Efficacy and Safety of Rivaroxaban Versus Aspirin in Embolic Stroke of Undetermined Source and Carotid Atherosclerosis


Por: Ntaios, G, Swaminathan, B, Berkowitz, SD, Gagliardi, RJ, Lang, W, Siegler, JE, Lavados, P, Mundl, H, Bornstein, N, Meseguer, E, Amarenco, P, Cucchiara, B, Camps-Renom, P, Makaritsis, K, Korompoki, E, Papavasileiou, V, Marti-Fabregas, J, Milionis, H, Vemmos, K, Connolly, SJ, Hart, RG, NAVIGATE ESUS Investigators

Publicada: 1 sep 2019
Resumen:
Background and Purpose- The sources of emboli in patients with embolic stroke of undetermined source (ESUS) are multiple and may not respond uniformly to anticoagulation. In this exploratory subgroup analysis of patients with carotid atherosclerosis in the NAVIGATE (New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism)-ESUS trial, we assessed whether the treatment effect in this subgroup is consistent with the overall trial population and investigated the association of carotid atherosclerosis with recurrent ischemic stroke. Methods- Carotid atherosclerosis was analyzed either as the presence of mild (ie, 20%-49%) atherosclerotic stenosis or, separately, as the presence of carotid plaque. Primary efficacy outcome was ischemic stroke recurrence. Safety outcomes were major bleeding and symptomatic intracerebral bleeding. Results- Carotid plaque was present in 40% of participants and mild carotid stenosis in 11%. There was no significant difference in ischemic stroke recurrence between rivaroxaban- and aspirin-treated patients among 490 patients with carotid stenosis (5.0 versus 5.9/100 patient-years, respectively, hazard ratio [HR], 0.85; 95% CI, 0.39-1.87; P for interaction of treatment effect with patients without carotid stenosis 0.78) and among 2905 patients with carotid plaques (5.9 versus 4.9/100 patient-years, respectively, HR, 1.20; 95% CI, 0.86-1.68; P for interaction of treatment effect with patients without carotid stenosis 0.2). Among patients with carotid plaque, major bleeding was more frequent in rivaroxaban-treated patients compared with aspirin-treated (2.0 versus 0.5/100 patient-years, HR, 3.75; 95% CI, 1.63-8.65). Patients with carotid stenosis had similar rate of ischemic stroke recurrence compared with those without (5.4 versus 4.9/100 patient-years, respectively, HR, 1.11; 95% CI, 0.73-1.69), but there was a strong trend of higher rate of ischemic stroke recurrence in patients with carotid plaque compared with those without (5.4 versus 4.3/100 patient-years, respectively, HR, 1.23; 95% CI, 0.99-1.54). Conclusions- In ESUS patients with carotid atherosclerosis, we found no difference in efficacy between rivaroxaban and aspirin for prevention of recurrent stroke, but aspirin was safer, consistent with the overall trial results. Carotid plaque was much more often present ipsilateral to the qualifying ischemic stroke than contralateral, supporting an important etiological role of nonstenotic carotid disease in ESUS.

Filiaciones:
Ntaios, G:
 Univ Thessaly, Dept Internal Med, Larisa, Greece

Swaminathan, B:
 Populat Hlth Res Inst, Hamilton, ON, Canada

Berkowitz, SD:
 Bayer US LLC, Pharmaceut Clin Dev Thrombosis, Whippany, NJ USA

Gagliardi, RJ:
 Irmandade Santa Casa Misericordia Sao Paulo, Sao Paulo, Brazil

Lang, W:
 Sigmund Freud Private Univ, Hosp St John God, Med Fac, Vienna, Austria

Siegler, JE:
 Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA

Lavados, P:
 Clin Alemana Santiago, Santiago, Chile

Mundl, H:
 Bayer AG, Wuppertal, Germany

Bornstein, N:
 Shaare Zedek Med Ctr Jerusalem, Jerusalem, Israel

Meseguer, E:
 Hop Xavier Bichat, Neurol Serv, Paris, France

Amarenco, P:
 Sorbonne Paris Cite Univ, Paris Diderot, Bichat Hosp, AP HP, Paris, France

Cucchiara, B:
 Hosp Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA

Camps-Renom, P:
 Hosp Santa Creu & Sant Pau, Serv Neurol, Unitat Malalties Vasc Cerebrals, Barcelona, Spain

Makaritsis, K:
 Univ Thessaly, Dept Internal Med, Larisa, Greece

Korompoki, E:
 Imperial Coll London, Charing Cross Hosp, Div Brain Sci, London, England

 Univ Athens, Sch Med, Dept Clin Therapeut, Athens, Greece

Papavasileiou, V:
 Univ Leeds, Sch Med, Leeds Teaching Hosp NHS Trust, Stroke Med, Leeds, W Yorkshire, England

Marti-Fabregas, J:
 Hosp Santa Creu & Sant Pau, Serv Neurol, Unitat Malalties Vasc Cerebrals, Barcelona, Spain

Milionis, H:
 Univ Ioannina, Fac Med, Sch Hlth Sci, Ioannina, Greece

Vemmos, K:
 Hellen Cardiovasc Res Soc, Athens, Greece

Connolly, SJ:
 McMaster Univ, Populat Hlth Res Inst, Dept Med Cardiol, Hamilton, ON, Canada

Hart, RG:
 McMaster Univ, Populat Hlth Res Inst, Dept Med Neurol, Hamilton, ON, Canada
ISSN: 00392499





STROKE
Editorial
LIPPINCOTT WILLIAMS & WILKINS, TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA, Estados Unidos America
Tipo de documento: Article
Volumen: 50 Número: 9
Páginas: 2477-2485
WOS Id: 000482956400056
ID de PubMed: 31401971
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