# Concomitant use of sivelestat sodium hydrate and antithrombotic drugs worsens the treatment outcome of patients with acute respiratory distress syndrome and suppression of fibrinolysis: a single-center, retrospective study

## TL;DR

This study found that combining sivelestat sodium hydrate with antithrombotic drugs may worsen outcomes for acute respiratory distress syndrome patients with suppressed fibrinolysis.

## Contribution

The study identifies a potential negative interaction between sivelestat and antithrombotic drugs in ARDS patients with suppressed fibrinolysis.

## Key findings

- SSH treatment did not improve 28-day mortality in ARDS patients with suppression of fibrinolysis.
- Combining SSH with antithrombotic drugs increased 28-day mortality in the SF group but not in the HF group.
- The FDP/D-dimer ratio effectively stratified patients into SF and HF groups for analysis.

## Abstract

Sivelestat sodium hydrate (SSH) may be effective in the early stage of acute respiratory distress syndrome (ARDS) before the neutrophil extracellular trap scaffold structure is complete. Therefore, patients with suppression of fibrinolysis (SF) before the secondary fibrinolytic process might benefit from SSH administration. The primary aim of this study was to determine the effect of the SF state and combination therapy on the effect of SSH administration.

We retrospectively reviewed the data of patients diagnosed with ARDS at Fujita Health University Hospital between July 2005 and December 2016. Patients with ARDS were stratified into the SF and hyperfibrinolysis (HF) groups. Using the fibrin degradation product (FDP)/D-dimer ratio, cut-off values were set as follows: FDP/D-dimer >2 for the HF group and FDP/D-dimer ≤2 for the SF group. The 28-day mortality was the primary endpoint.

In total, 168 patients (71 in the HF group and 97 in the SF group) were included in the analysis. The mortality within 28 days was not different based on SSH administration in either group (HF group: p=0.956, SF group: p=0.957). In the SF group, the mortality rate within 28 days in SSH-treated patients who received antithrombotic drugs was significantly higher than that in patients who received SSH only (p<0.05). However, this finding was not present in the HF group (p=0.786).

Concomitant use of SSH and antithrombotic drugs might worsen the treatment outcome of patients with ADRS in the SF state.