ESC 2026 Stroke Spotlight Recap: 5 Practice-Changing Trials to Know

The European Society of Cardiology (ESC) Congress 2026 in Munich, Germany, saw a substantial amount of new information related to the treatment and prevention of stroke. Oral anticoagulants and AI demonstrated their protective capacity for several forms of stroke, while NOAC monotherapy reduced subclinical leaflet thrombosis after transcatheter aortic valve implantation. However, not all major trials presented over the 4 days of the conference succeeded: ENRICH-AF and LIBREXIA ACS both failed to meet their primary endpoints.

Of course, even a failed trial still serves an educational or informative purpose, and with so many trials presented in the stroke space during this conference, the HCPLive editorial team has collected 5 of the most impactful headlines to release at ESC 2026. Catch up on any stroke information you may have missed below:

ORFAN-MAESTRIA: AI Predicts Cardioembolic Stroke, Atrial Fibrillation from CT Scans

The ORFAN-MAESTRIA trial, enrolling >80,000 patients and lasting for 10 years, displayed the efficacy of AI deep learning models in identifying and predicting cardioembolic stroke and atrial fibrillation from routine computed tomography (CT) scans. Presented by Charalambos Antoniades, MD, PhD, director of the Acute Multidisciplinary Imaging & Interventional Centre and founder and chief scientific officer at Caristo Diagnostics, the trial opens up a new pathway to identifying atrial myopathy before it occurs and preventing the ensuing cardiovascular damage.

ACASA-TAVI: NOAC Monotherapy Cuts Leaflet Thrombosis

Anticoagulation monotherapy after transcatheter aortic valve implantation demonstrated a significant reduction in subclinical leaflet thrombosis while remaining noninferior for bleeding, thromboembolic events, and death compared with antiplatelet monotherapy. ACASA-TAVI, presented by Øyvind Lie, MD, PhD, MSc, of Oslo University Hospital Rikshospitalet and the principal investigator in the trial, represents a direct contradiction to the widely-accepted belief that oral anticoagulants carry a higher bleeding risk for these patients.

ENRICH-AF: A Dosing Clue Emerges After Edoxaban's Miss, With Ashkan Shoamanesh, MD

ENRICH-AF is the largest randomized trial conducted in patients with atrial fibrillation and intracranial hemorrhage. However, edoxaban treatment failed to significantly reduce the primary composite endpoint of stroke or systemic embolism compared with no anticoagulation and led to greater rates of ISTH major bleeding in treated patients. In an interview with HCPLive, Ashkan Shoamanesh, MD, of McMaster University, principal investigator of the trial, discusses the tradeoff between the slightly reduced stroke risk and the substantially increased bleeding risk.

LIBREXIA ACS Fails to Improve Cardiovascular Outcomes, Doesn’t Increase Bleeding Risk

The LIBREXIA ACS study, aiming to investigate milvexian in reducing cardiovascular events following acute coronary syndrome, ultimately failed to achieve superiority to placebo and was terminated early. Despite this, as Philippe Gabriel Steg, MD, professor of cardiology at the Université Paris, stated in an interview with HCPLive, milvexian’s investigative pathway is far from over – the ongoing LIBREXIA-AF and LIBREXIA-Stroke trials, reporting in 2027, will further delve into the drug’s potential cardioprotective effects.

SINGLE-AF: Oral Anticoagulants Reduce Risk of Stroke in Patients With AF

The evidence to support anticoagulants in patients with atrial fibrillation who are at intermediate risk of stroke has traditionally been conflicting. The SINGLE-AF trial, presented by Boyoung Joung, MD, from the Yonsei University College of Medicine in South Korea, took the first step towards redefining this treatment method in this population. With a total of 1803 patients enrolled, the trial demonstrated a substantial reduction in a composite endpoint of stroke, systemic embolism, major bleeding, and cardiovascular death over 24 months.