Non-Valvular Atrial Fibrillation and Acute Stroke: Prevention and Management

Dear Colleagues,

The incidence of non-valvular atrial fibrillation (NVAF) increases steadily with age and this condition represents one of the leading causes of acute ischemic stroke (AIS), especially in patients 65 years in age and older. Moreover, NVAF represents the most frequent underlying cause of embolic stroke of undetermined source (ESUS), supporting the need for screening using non-implantable or implantable ECG monitoring devices.

NVAF-related AIS displays the highest rates of mortality, morbidity, and functional residual disability compared with the other causes of AIS. Therefore, there are efforts to avoid this using primary and secondary prevention; reperfusive treatments in the acute phase of AIS, such as systemic intravenous thrombolysis and/or mechanical thrombectomy, are of paramount importance. Systemic intravenous thrombolysis and/or mechanical thrombectomy present higher rates of complications in patients with NVAF-related AIS, mainly due to the higher frequency of large-vessel occlusions (LVOs). 

Despite oral anticoagulant therapy (OAT), a technique using direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), representing the main therapeutic option for the primary and secondary prevention of cardioembolism in NVAF, the recent literature shows that the prevalence of NVAF-related AIS on prior OAT is increasing over the time, mainly due to the steady increase in the use of DOACs in recent years. The persistence of NVAF-related AIS, despite OAT, represents a conundrum and a challenge for stroke physicians, both in terms of the appropriate choice of reperfusive treatments in the hyperacute phase and in terms of secondary prevention due to the higher risk of recurrence. In DOAC patients, mechanical thrombectomy represents the best reperfusive treatment in the case of LVO in the time-dependent phase of AIS. However, there is increased evidence in the literature regarding the beneficial role of intravenous systemic thrombolysis in this context, mainly derived from case series of patients reaching the alteplase. The knowledge gap regarding the efficacy and safety of the new thrombolytic agent tenecteplase in patients with NVAF-related AIS, despite DOAC treatment, should be filled.

The appropriate timing of DOAC treatment in the acute phase of NVAF-related AIS is controversial. The recent evidence in the literature shows that the earlier starting point of DOAC treatment could be effective and safe compared with that recommended by previous international guidelines, suggesting the need to revise the abovementioned guidelines.

This is the most appropriate option for secondary prevention in NVAF-related AIS, despite the efficacy of OAT, constituting a conundrum. Switching from a DOAC to VKA or from DOAC to another DOAC in patients with non-competitive mechanisms of AIS seems to offer no benefit in terms of stroke recurrence, while the switch from DOAC to VKA increases the risk of non-major and major bleeds. Left atrial appendage occlusion (LAAO) seems to be a promising alternative to pharmacological prevention in these patients. Ongoing phase III randomized clinical trials, comparing LAAO with DOACs or comparing LAAO plus DOACs with DOACs alone, could provide evidence that may bridge this knowledge gap.

Hemorrhagic stroke is the most feared complication of patients on OAT for stroke prevention in NVAF. The reversal therapy involving OAT is the cornerstone of hemorrhagic stroke in this context. However, whether reversal therapy is associated with better functional outcomes in patients with OAT-related hemorrhagic stroke is controversial. For example, the net clinical benefit of re-starting DOACs in patients with DOAC-related hemorrhagic stroke is controversial. The evidence in the recent literature shows that re-starting DOACs after DOAC-related hemorrhagic stroke could be associated with a major risk of bleeding recurrence. 

This Special Issue invites the submission of original papers, reviews, systematic reviews, meta-analyses, commentaries, points of view, and clinical practice paths highlighting primary and secondary prevention and the management of time-dependent phase, hospital stay, and the outcomes of patients with NVAF-related AIS.

Dr. Luca Masotti
Guest Editor

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• atrial fibrillation
• acute ischemic stroke
• intracerebral hemorrhage
• direct oral anticoagulants
• vitamin K antagonists
• reversal therapy
• tenecteplase
• alteplase
• intravenous thrombolysis
• mechanical thrombectomy
• left atrial appendage occlusion
• embolic stroke of undetermined source
• ECG monitoring