# Predictive Role of Metabolic Profiling in Rivaroxaban Efficacy for Thrombus Lysis in Atrial Fibrillation

## TL;DR

This study explores how metabolic profiles can predict the effectiveness of rivaroxaban in dissolving blood clots in atrial fibrillation patients.

## Contribution

The study identifies specific metabolic markers that may predict rivaroxaban efficacy in thrombus lysis.

## Key findings

- Patients who responded to rivaroxaban showed elevated levels of acylcarnitines, carnitine, and its precursors.
- Metabolites related to fatty acid metabolism and arginine/proline pathways were differentially abundant in responders.
- Elevated levels of these metabolites may serve as potential biomarkers for treatment response.

## Abstract

Traditional anticoagulants used in atrial fibrillation (AF) are being increasingly replaced by novel oral anticoagulants such as rivaroxaban, improving patient outcomes. Although rivaroxaban 20 mg/1× daily is approved to reduce stroke and systemic embolism risk in AF, some patients still develop thrombus in the left atrial appendage (LAA). A previous study demonstrated thrombus lysis with a modified regimen of rivaroxaban 15 mg/2× daily, yet over 50% of patients remained unresponsive despite therapeutic plasma levels. This study compared metabolic profiles of responders and non-responders to identify predictive markers of treatment efficacy. From the RIVA-TWICE study cohort (n = 249), 15 AF patients with LAA thrombus despite standard dosing were switched to 2 × 15 mg rivaroxaban. Plasma samples collected prior to dose modification underwent untargeted and targeted LC-MS analysis, focusing on acylcarnitines (ACs), carnitine, and its precursors. Thrombus resolution occurred in 7 (46.7%) patients, who showed differential abundance of metabolites related to alpha-linolenic acid and fatty acid metabolism, carnitine synthesis, and arginine/proline pathways. Targeted analysis confirmed elevated levels of ACs, carnitine, and precursors. Findings suggest that a patient phenotype, including carnitine, its precursors, and ACs, may predict rivaroxaban efficacy in thrombus lysis. While these metabolites may not directly mediate lysis, their elevated levels represent potential biomarkers of treatment response.