Risk Factors for Intracerebral Hemorrhage in Patients With Atrial Fibrillation on Non–Vitamin K Antagonist Oral Anticoagulants for Stroke Prevention
Authors: Paciaroni Maurizio , Agnelli Giancarlo , Giustozzi Michela , Caso Valeria , Toso Elisabetta , Angelini Filippo , Canavero Isabella , Micieli Giuseppe , Antonenko Kateryna , Rocco Alessandro , Diomedi Marina , Katsanos Aristeidis H. , Shoamanesh Ashkan , Giannopoulos Sotirios , Ageno Walter , Pegoraro Samuela , Putaala Jukka , Strbian Daniel , Sallinen Hanne , Mac Grory Brian C. , Furie Karen L. , Stretz Christoph , Reznik Michael E. , Alberti Andrea , Venti Michele , Mosconi Maria Giulia , Vedovati Maria Cristina , Franco Laura , Zepponi Giorgia , Romoli Michele , Zini Andrea , Brancaleoni Laura , Riva Letizia , Silvestrelli Giorgio , Ciccone Alfonso , Zedde Maria Luisa , Giorli Elisa , Kosmidou Maria , Ntais Evangelos , Palaiodimou Lina , Halvatsiotis Panagiotis , Tassinari Tiziana , Saia Valentina , Ornello Raffaele , Sacco Simona , Bandini Fabio , Mancuso Michelangelo , Orlandi Giovanni , Ferrari Elena , Pezzini Alessandro , Poli Loris , Cappellari Manuel , Forlivesi Stefano , Rigatelli Alberto , Yaghi Shadi , Scher Erica , Frontera Jennifer A. , Masotti Luca , Grifoni Elisa , Caliandro Pietro , Zauli Aurelia , Reale Giuseppe , Marcheselli Simona , Gasparro Antonio , Terruso Valeria , Arnao Valentina , Aridon Paolo , Abdul-Rahim Azmil H. , Dawson Jesse , Saggese Carlo Emanuele , Palmerini Francesco , Doronin Boris , Volodina Vera , Toni Danilo , Risitano Angela , Schirinzi Erika , Del Sette Massimo , Lochner Piergiorgio , Monaco Serena , Mannino Marina , Tassi Rossana , Guideri Francesca , Acampa Maurizio , Martini Giuseppe , Lotti Enrico Maria , Padroni Marina , Pantoni Leonardo , Rosa Silvia , Bertora Pierluigi , Ntaios George , Sagris Dimitrios , Baldi Antonio , D’Amore Cataldo , Mumoli Nicola , Porta Cesare , Denti Licia , Chiti Alberto , Corea Francesco , Acciarresi Monica , Flomin Yuriy , Popovic Nemanja , Tsivgoulis Georgios 
Published: March 2021

Background and Purpose:

Clinical trials on stroke prevention in patients with atrial fibrillation have consistently shown clinical benefit from either warfarin or non–vitamin K antagonist oral anticoagulants (NOACs). NOAC-treated patients have consistently reported to be at lower risk for intracerebral hemorrhage (ICH) than warfarin-treated patients. The aims of this prospective, multicenter, multinational, unmatched, case-control study were (1) to investigate for risk factors that could predict ICH occurring in patients with atrial fibrillation during NOAC treatment and (2) to evaluate the role of CHA
2
DS
2
-VASc and HAS-BLED scores in the same setting.

Methods:

Cases were consecutive patients with atrial fibrillation who had ICH during NOAC treatment. Controls were consecutive patients with atrial fibrillation who did not have ICH during NOAC treatment. As within the CHA
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DS
2
-VASc and HAS-BLED scores there are some risk factors in common, several multivariable logistic regression models were performed to identify independent prespecified predictors for ICH events.

Results:

Four hundred nineteen cases (mean age, 78.8±8.1 years) and 1526 controls (mean age, 76.0±10.3 years) were included in the study. From the different models performed, independent predictors of ICH were increasing age, concomitant use of antiplatelet agents, active malignancy, high risk of fall, hyperlipidemia, low clearance of creatinine, peripheral artery disease, and white matter changes. Low doses of NOACs (given according to label or not) and congestive heart failure were inversely associated with the risk of ICH. HAS-BLED and CHA
2
DS
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-VASc scores performed poorly in predicting ICH with areas under the curves of 0.496 (95% CI, 0.468–0.525) and 0.530 (95% CI, 0.500–0.560), respectively.

Conclusions:

Several risk factors were associated to ICH in patients treated with NOACs for stroke prevention but not HAS-BLED and CHA
2
DS
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-VASc scores.