Statin therapy in ischemic stroke patients with atrial fibrillation: Efficacy and safety outcomes
Authors: Marvardi Michele , Paciaroni Maurizio , Caso Valeria , Marvardi Michele , Ferrante Mario , Abdul-Rahim Azmil , Georgios Tsivgoulis MD , Julian Seiffge David , Engelter Stefan T. , Lyrer Philippe , Polymeris Alexandros A. , Dittrich Tolga , Cancelloni Virginia , Zietz Annaelle , Marco De Marchis Gian , Putaala Jukka , Strbian Daniel , Tomppo Liisa , Michel Patrik , Strambo Davide , Salerno Alexander , Vanacker Peter , Zuurbier Susanna , Yperzeele Laetitia , Loos Caroline M.J. , Cappellari Manuel , Emiliani Andrea , Zedde Marialuisa , Becattini Cecilia , Pascarella Rosario , Dawson Jesse , Cronshaw Robert , Schirinzi Erika , Del Sette Massimo , Stretz Christoph , Kala Narendra , Schomer Ashley , Mac Grory Brian , Jayaraman Mahesh , Yaghi Shadi , Furie Karen L. , Masotti Luca , Grifoni Elisa , Toni Danilo , Risitano Angela , Falcou Anne , Petraglia Luca , Maria Lotti Enrico , Pavolucci Lucia , Lochner Piergiorgio , Silvestrelli Giorgio , Ciccone Alfonso , Alberti Andrea , Venti Michele , Leone De Magistris Ilaria , Giulia Mosconi Maria , Giustozzi Michela , Kargiotis Odysseas , Rocco Alessandro , Diomedi Marina , Marcheselli Simona , 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 , Adamou Anastasia , Sagris Dimitrios , Giannopoulos Sotirios , Kosmidou Maria , Ntais Evangelos , Romoli Michele , Pantoni Leonardo , Rosa Silvia , Bertora Pierluigi , Chiti Alberto , Canavero Isabella , Emanuele Saggese Carlo , Plocco Maurizio , Giorli Elisa , Palaiodimou Lina , Bakola Eleni , Bandini Fabio , Gasparro Antonio , Terruso Valeria , Mannino Marina , Pezzini Alessandro , Ornello Raffaele , Sacco Simona , Popovic Nemanja , Scoditti Umberto , Genovese Antonio , Flomin Yuriy , Mancuso Michelangelo , D’Agliano Roberto , Baldini Marco , Ulivi Leonardo , Giannini Nicola , Vadikolias Kostantinos , Liantinioti Chrysoula , Chondrogianni Maria , Halvatsiotis Panagiotis , Karagkiozi Efstathia , Athanasakis George , Makaritsis Kostantinos , Lanari Alessia , Tatlisumak Turgut , Acciarresi Monica , Lorenzini Gianni , Tassi Rossana , Guideri Francesca , Acampa Maurizio , Martini Giuseppe , Sohn Sung-Il , Mumoli Nicola , Carrara Davide , Maccarrone Miriam , Galati Franco , Gourbali Vanessa , Orlandi Giovanni , Giuntini Martina , Corea Francesco , Bellesini Marta , Karapanayiotides Theodore , Csiba Laszló , Szabó Lilla , Imberti Davide , Pieroni Alessio , Barlinn Kristian , Pallesen Lars-Peder , Barlinn Jessica , Doronin Boris , Volodina Vera , Agnelli Giancarlo , Deleu Dirk , Bonetti Bruno , Gentile Luana , Reale Giuseppe , Caliandro Pietro , Morotti Andrea , Vannucchi Vieri , Padroni Marina , Letteri Federica , Magoni Mauro , Tiseo Cindy , Rigatelli Alberto , Zauli Aurelia , Bossi Francesco , Paciaroni Maurizio , Caso Valeria 
Published: January 2025

Introduction: The efficacy and safety of statins for secondary prevention in patients who have experienced a cardioembolic stroke are not well-defined. However, previous observational data reported hyperlipidemia as a risk factor for both ischemic and bleeding complications in patients with AF and previous stroke. Based on these premises, we conducted a sub-analysis of the RAF and RAF-NOAC studies to evaluate the efficacy and safety of statins in secondary prevention in patients with acute ischemic stroke and AF. Materials and methods: We combined patient data from the RAF and RAF-NOAC studies, prospective observational studies conducted across Stroke Units in Europe, the United States, and Asia from January 2012 to June 2016. We included consecutive patients with AF who suffered an acute ischemic stroke with a follow-up of 90 days. Our outcomes were the combined endpoint, including stroke, transient ischemic attack, systemic embolism, symptomatic intracerebral hemorrhage, and major extracranial bleeding. Furthermore, both ischemic and hemorrhagic outcomes were evaluated separately. Results: A total of 1742 patients were included (46% male), and 898 (52%) received statins after the index event, of whom 436 (48.6%) were already taking statins before the index event, 462 (51.4%) started treatment after. At multivariable analysis, statin use was statistically associated with age (OR 0.92, 95% CI 0.97–0.99, p = 0.001), male sex (OR 1.35, 95% CI 1.07–1.70, p = 0.013), anticoagulation (OR 2.53, 95% CI 1.90–3.36, p < 0.0001), hyperlipidemia (OR 5.52, 95% CI 4.28–7.12, p < 0.0001), paroxysmal AF (OR 1.40, 95% CI 1.12–1.75, p = 0.003), leukoaraiosis (OR 1.39, 95% CI 1.11–1.75, p = 0.004) and heart failure (OR 0.72, 95% CI 0.53–0.98, p = 0.034). Statin use was not associated with the combined outcome event (OR 0.84, 95% CI 0.58–1.23, p = 0.3) and ischemic outcome event (OR 1.17, 95% CI 0.73–1.88, p = 0.5) while was associated with a lower risk of hemorrhagic outcome event (OR 0.51, 95% CI 0.28–0.91, p = 0.02). Discussion: Statins protect cerebral arterial vessels (particularly small vessels) from subacute damage due to hypertension, diabetes, and other harmful agents (such as reactive oxygen species, proinflammatory cytokines, etc.) due to their systemic anti-inflammatory and endothelium-protective effects. Conclusions: Our data show that statins seem to protect against global bleeding events in cardioembolic stroke patients; this may be due to the pleiotropic effect of statins. More data are warranted to confirm these findings.