Transport Strategy in Patients With Suspected Acute Large Vessel Occlusion Stroke: TRIAGE-STROKE, a Randomized Clinical Trial.

BACKGROUND: When patients with acute ischemic stroke present with suspected large vessel occlusion in the catchment area of a primary stroke center (PSC), the benefit of direct transport to a comprehensive stroke center (CSC) has been suggested. Equipoise remains between transport strategies and the best transport strategy is not well established. METHODS: We conducted a national investigator-driven, multicenter, randomized, assessor-blinded clinical trial. Patients eligible for intravenous thrombolysis (IVT) who were suspected for large vessel occlusion were randomized 1:1 to admission to the nearest PSC (prioritizing IVT) or direct CSC admission (prioritizing endovascular therapy). The primary outcome was functional improvement at day 90 for all patients with acute ischemic stroke, measured as shift towards a lower score on the modified Rankin Scale score. RESULTS: From September 2018 to May 2022, we enrolled 171 patients of whom 104 had acute ischemic stroke. The trial was halted before full recruitment. Baseline characteristics were well balanced. Primary analysis of shift in modified Rankin Scale (ordinal logistic regression) revealed an odds ratio for functional improvement at day 90 of 1.42 (95% CI, 0.72-2.82, P=0.31). Onset to groin time for patients with large vessel occlusion was 35 minutes (P=0.007) shorter when patients were transported to a CSC first, whereas onset to needle (IVT) was 30 minutes (P=0.012) shorter when patients were transported to PSC first. IVT was administered in 67% of patients in the PSC group versus 78% in the CSC group and EVT was performed in 53% versus 63% of the patients, respectively. CONCLUSIONS: This trial investigated the benefit of bypassing PSC. We included only IVT-eligible patients presenting <4 hours from onset and with suspected large vessel occlusion. Lack of power prevented the results from showing effect on functional outcome for patients going directly to CSC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03542188.

Left atrial appendage occlusion vs novel oral anticoagulation for stroke prevention in atrial fibrillation: rationale and design of the multicenter randomized occlusion-AF trial.

BACKGROUND: The prevalence of atrial fibrillation (AF) is increasing globally, which is a major clinical and public health concern due to the 5-fold increased risk of stroke. Oral anticoagulation with novel oral anticoagulants (NOACs) is the current primary option for stroke prevention in patients with AF, although it increases the risk of major bleeding. Patients with prior ischemic cerebrovascular events are at particularly high risk of both recurrent ischemic events and major bleeding. Left atrial appendage occlusion (LAAO) provides an alternative option for stroke prevention in high-risk patients, however, with currently limited evidence. Thus, randomized trials comparing LAAO to NOACs are needed. OBJECTIVE: The Occlusion-AF trial is designed to assess whether LAAO is non-inferior to NOAC therapy for reduction of the combined endpoint of stroke, systemic embolism, major bleeding (Bleeding Academic Research Consortium ≥ 3) and all-cause mortality in patients with AF and a recent ischemic stroke or transient ischemic attack (TIA). METHODS AND ANALYSIS: Investigator-initiated multicenter, multinational, randomized open-label non-inferiority trial with blinded outcome evaluation (PROBE design). Patients with documented AF, and an ischemic stroke or TIA within 6 months will be eligible for enrollment. Major exclusion criteria are modified Rankin Scale > 3 at enrollment, glomerular filtration rate < 15 ml/min, and life-expectancy less than 2 years. A total of 750 patients will be randomized 1:1 to receive either a NOAC or LAAO using the Amplatzer Amulet (Abbott, MN, USA) or Watchman FLX (Boston Scientific, MN, USA) with subsequent life-long aspirin 75 mg daily. Follow-up will be based on in-office and telephone follow-up in combination with long-term follow-up (10 years) through national hospital discharge registries in the individual Nordic countries. The primary outcome will be a composite endpoint of stroke, systemic embolism, major bleeding (BARC ≥ 3) and all-cause mortality at 2-year follow-up. CONCLUSIONS: The Occlusion-AF trial is designed to compare LAAO to NOAC therapy for secondary stroke prevention in AF patients with a high risk of recurrent thromboembolic events, i.e. with previous ischemic stroke or TIA, and otherwise eligible for anticoagulation. The results are expected to contribute significantly to the understanding of the effects of LAAO compared to the standard contemporary pharmacological treatment in these patients.