# The left atrial appendage closure by surgery 2 trial: statistical analysis plan for a randomized multicenter trial exploring if the closure of the left atrial appendage during open-heart surgery reduces stroke irrespective of patients’ stroke risk and preoperative atrial fibrillation status

## TL;DR

This trial aims to determine if closing the left atrial appendage during open-heart surgery reduces stroke risk regardless of patients' stroke risk or atrial fibrillation status.

## Contribution

The study provides a statistical analysis plan for a randomized trial on left atrial appendage closure in diverse patient populations.

## Key findings

- The trial will enroll 1500 patients and follow them for 2 years to assess stroke outcomes.
- LAA closure is expected to reduce stroke risk by 60% relative to standard care.
- Blinded neurologists will assess outcomes to minimize bias.

## Abstract

Surgical left atrial appendage (LAA) closure concomitant to open-heart surgery prevents thromboembolism in high-risk patients. Nevertheless, high-level evidence does not exist for LAA closure performed in patients with any CHA2DS2-VASc score and preoperative atrial fibrillation or flutter (AF) status—the current trial attempts to provide such evidence.

The study is designed as a randomized, open-label, blinded outcome assessor, multicenter trial of adult patients undergoing first-time elective open-heart surgery. Patients with and without AF and any CHA2DS2-VASc score will be enrolled. The primary exclusion criteria are planned LAA closure, planned AF ablation, or ongoing endocarditis. Before randomization, a three-step stratification process will sort patients by site, surgery type, and preoperative or expected oral anticoagulation treatment. Patients will undergo balanced randomization (1:1) to LAA closure on top of the planned cardiac surgery or standard care. Block sizes vary from 8 to 16. Neurologists blinded to randomization will adjudicate the primary outcome of stroke, including transient ischemic attack (TIA). The secondary outcomes include a composite outcome of stroke, including TIA, and silent cerebral infarcts, an outcome of ischemic stroke, including TIA, and a composite outcome of stroke and all-cause mortality. LAA closure is expected to provide a 60% relative risk reduction. In total, 1500 patients will be randomized and followed for 2 years.

The trial is expected to help form future guidelines within surgical LAA closure. This statistical analysis plan ensures transparency of analyses and limits potential reporting biases.

Clinicaltrials.gov, NCT03724318. Registered 26 October 2018, https://clinicaltrials.gov/study/NCT03724318.

10.1016/j.ahj.2023.06.003.

The online version contains supplementary material available at 10.1186/s13063-024-08122-9. The SAP checklist is supplied in the supplementary material.