Evaluation of Non-Vitamin K Oral Anticoagulants for Stroke Prevention in Patients with Perioperative Atrial Fibrillation Post-Noncardiac Surgery

The primary objective of the ASPIRE-AF trial is to evaluate the effects of **non-vitamin K oral anticoagulants (NOACs)** compared to no anticoagulation on the co-primary composite outcomes. These outcomes include non-hemorrhagic stroke and systemic embolism, as well as vascular mortality, non-fatal non-hemorrhagic stroke, myocardial infarction, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism over the duration of follow-up. This is clinically relevant as it aims to determine the efficacy of NOACs in preventing serious cardiovascular events in patients with perioperative atrial fibrillation after noncardiac surgery, potentially guiding treatment decisions to improve patient outcomes.

Secondary objectives include:

• Assessing the effects of NOACs on the incidence of individual components of the co-primary outcomes.
• Evaluating the effects of NOACs on the incidence of all stroke.
• Determining the effects of NOACs on the incidence of all-cause mortality.

The clinical trial involves a total of **1660 participants** who have experienced **perioperative atrial fibrillation** following noncardiac surgery. The study population includes both male and female subjects, with an age range primarily between 55 and 75 years. Participants were selected based on specific criteria, including having undergone noncardiac surgery within the past 35 days and experiencing at least one episode of clinically significant perioperative atrial fibrillation. The trial includes individuals in sinus rhythm at the time of randomization and those meeting high-risk criteria, such as established cardiovascular disease or elevated postoperative troponin levels. The study population is characterized by a mix of general health statuses, with a focus on those who have had recent major vascular surgery or possess a CHA2DS2VASc score indicative of increased risk. The trial does not specify particular lifestyle considerations such as diet or physical activity. Both vulnerable and non-vulnerable populations are included, ensuring a comprehensive assessment of the effects of non-vitamin K oral anticoagulants versus no anticoagulation on various cardiovascular outcomes.

The clinical trial is designed to evaluate the safety and efficacy of non-vitamin K oral anticoagulants (**NOACs**) in patients with perioperative atrial fibrillation following noncardiac surgery. This is a Phase IV, randomized, double-blind, controlled trial. The trial aims to assess the effects of NOACs versus no anticoagulation on co-primary composite outcomes, including non-hemorrhagic stroke, systemic embolism, vascular mortality, and other related vascular events. The trial is expected to run until June 2028, with recruitment having commenced in November 2020.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as recent noncardiac surgery and episodes of perioperative atrial fibrillation. Following randomization, participants will receive either a NOAC or placebo, administered orally, with dosages varying based on the specific anticoagulant used. The maximum treatment period is 120 days. Follow-up visits will be scheduled to monitor the participants' health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will conclude the trial for each participant, assessing the primary and secondary endpoints.

Participant involvement is expected to last for the duration of the treatment period, with conditions for early termination including withdrawal of consent, significant adverse events, or protocol non-compliance. The trial's primary endpoints include the individual components of the co-primary outcomes, all stroke occurrences, and all-cause mortality. The trial does not specify secondary endpoints. The study is not categorized as low intervention, given its focus on evaluating the safety and efficacy of approved NOACs in a high-risk population.

The clinical trial involves the administration of several **anticoagulant** medications, each with specific dosing regimens and administration routes. **Apixaban** is utilized in two different dosages. The first formulation is a tablet with a maximum daily dose of 2.5 mg, administered orally. The second formulation also in tablet form, has a maximum daily dose of 5 mg, administered orally. Both formulations are intended for a maximum treatment period of 120 days.

**Edoxaban** is administered in two different dosages as well. The first formulation is a film-coated tablet with a maximum daily dose of 30 mg, administered orally. The second formulation, also a film-coated tablet, has a maximum daily dose of 60 mg, administered orally. Both formulations are intended for a maximum treatment period of 120 days.

**Rivaroxaban** is provided in two dosages. The first formulation is a film-coated tablet with a maximum daily dose of 15 mg, administered orally. The second formulation, also a film-coated tablet, has a maximum daily dose of 20 mg, administered orally. Both formulations are intended for a maximum treatment period of 120 days.

**Dabigatran** is administered as a capsule with a maximum daily dose of 110 mg, administered orally. This formulation is also intended for a maximum treatment period of 120 days.

All medications are administered orally, and participant compliance is monitored throughout the trial. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The primary objective is to assess the effects of these non-vitamin K oral anticoagulants on specific clinical outcomes related to stroke prevention in patients with recent episodes of perioperative atrial fibrillation after noncardiac surgery.

The efficacy of the clinical trial titled "Anticoagulation for Stroke Prevention In patients with Recent Episodes of perioperative Atrial Fibrillation after noncardiac surgery - The ASPIRE-AF trial" will be assessed through the evaluation of co-primary composite outcomes. These outcomes include non-hemorrhagic stroke and systemic embolism, as well as vascular mortality, non-fatal non-hemorrhagic stroke, myocardial infarction, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary endpoints for efficacy assessment are the individual components of the co-primary outcomes, all stroke, and all-cause mortality.

The trial will compare the effects of non-vitamin K oral anticoagulants (NOACs) versus no anticoagulation. The assessment will be conducted over the duration of the follow-up period, which is planned to last up to 120 days for each participant. The trial is a Phase IV clinical trial, focusing on the safety and efficacy of approved NOACs in patients with atrial fibrillation after noncardiac surgery who are at high risk of stroke. The trial is not categorized as low intervention, indicating a comprehensive evaluation of the treatment's impact on the specified endpoints.