Recurrent Ischemic Stroke and Bleeding in Patients With Atrial Fibrillation Who Suffered an Acute Stroke While on Treatment With Nonvitamin K Antagonist Oral Anticoagulants: The RENO-EXTEND Study
Authors: Paciaroni Maurizio , Caso Valeria , Agnelli Giancarlo , Mosconi Maria Giulia , Giustozzi Michela , Seiffge David Julian , Engelter Stefan T. , Lyrer Philippe , Polymeris Alexandros A. , Kriemler Lilian , Zietz Annaelle , Putaala Jukka , Strbian Daniel , Tomppo Liisa , Michel Patrik , Strambo Davide , Salerno Alexander , Remillard Suzette , Buehrer Manuela , Bavaud Odessa , Vanacker Peter , Zuurbier Susanna , Yperzeele Laetitia , Loos Caroline M.J. , Cappellari Manuel , Emiliani Andrea , Zedde Marialuisa , Abdul-Rahim Azmil , Dawson Jesse , Cronshaw Robert , Schirinzi Erika , Del Sette Massimo , Stretz Christoph , Kala Narendra , Reznik Michael , Schomer Ashley , Grory Brian Mac , Jayaraman Mahesh , McTaggart Ryan , Yaghi Shadi , Furie Karen L. , Masotti Luca , Grifoni Elisa , Toni Danilo , Risitano Angela , Falcou Anne , Petraglia Luca , Lotti Enrico Maria , Padroni Marina , Pavolucci Lucia , Lochner Piergiorgio , Silvestrelli Giorgio , Ciccone Alfonso , Alberti Andrea , Venti Michele , Traballi Laura , Urbini Chiara , Kargiotis Odysseas , Rocco Alessandro , Diomedi Marina , Marcheselli Simona , Caliandro Pietro , Zauli Aurelia , Reale Giuseppe , Antonenko Kateryna , Rota Eugenia , Tassinari Tiziana , Saia Valentina , Palmerini Francesco , Aridon Paolo , Arnao Valentina , Monaco Serena , Cottone Salvatore , Baldi Antonio , D’Amore Cataldo , Ageno Walter , Pegoraro Samuela , Ntaios George , Sagris Dimitrios , Giannopoulos Sotirios , Kosmidou Maria , Ntais Evangelos , Romoli Michele , Pantoni Leonardo , Rosa Silvia , Bertora Pierluigi , Chiti Alberto , Canavero Isabella , Saggese Carlo Emanuele , Plocco Maurizio , Giorli Elisa , Palaiodimou Lina , Bakola Eleni , Tsivgoulis Georgios , Bandini Fabio , Gasparro Antonio , Terruso Valeria , Mannino Marina , Pezzini Alessandro , Ornello Raffaele , Sacco Simona , Popovic Nemanja , Scoditti Umberto , Genovese Antonio , Denti Licia , Flomin Yuriy , Mancuso Michelangelo , Ferrari Elena , Caselli Maria Chiara , Ulivi Leonardo , Giannini Nicola , De Marchis Gian Marco 
Published: May 2022

Background:
In patients with atrial fibrillation who suffered an ischemic stroke while on treatment with nonvitamin K antagonist oral anticoagulants, rates and determinants of recurrent ischemic events and major bleedings remain uncertain.

Methods:
This prospective multicenter observational study aimed to estimate the rates of ischemic and bleeding events and their determinants in the follow-up of consecutive patients with atrial fibrillation who suffered an acute cerebrovascular ischemic event while on nonvitamin K antagonist oral anticoagulant treatment. Afterwards, we compared the estimated risks of ischemic and bleeding events between the patients in whom anticoagulant therapy was changed to those who continued the original treatment.

Results:

After a mean follow-up time of 15.0±10.9 months, 192 out of 1240 patients (15.5%) had 207 ischemic or bleeding events corresponding to an annual rate of 13.4%. Among the events, 111 were ischemic strokes, 15 systemic embolisms, 24 intracranial bleedings, and 57 major extracranial bleedings. Predictive factors of recurrent ischemic events (strokes and systemic embolisms) included CHA
2
DS
2
-VASc score after the index event (odds ratio [OR], 1.2 [95% CI, 1.0–1.3] for each point increase;
P
=0.05) and hypertension (OR, 2.3 [95% CI, 1.0–5.1];
P
=0.04). Predictive factors of bleeding events (intracranial and major extracranial bleedings) included age (OR, 1.1 [95% CI, 1.0–1.2] for each year increase;
P
=0.002), history of major bleeding (OR, 6.9 [95% CI, 3.4–14.2];
P
=0.0001) and the concomitant administration of an antiplatelet agent (OR, 2.8 [95% CI, 1.4–5.5];
P
=0.003). Rates of ischemic and bleeding events were no different in patients who changed or not changed the original nonvitamin K antagonist oral anticoagulants treatment (OR, 1.2 [95% CI, 0.8–1.7]).

Conclusions:
Patients suffering a stroke despite being on nonvitamin K antagonist oral anticoagulant therapy are at high risk of recurrent ischemic stroke and bleeding. In these patients, further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischemic stroke and bleeding.