Landiolol Effectively Controls Heart Rate in Septic Shock Patients Without Increasing Vasopressor Needs: Landi-SEP Trial

"Landiolol effectively lowers and sustains heart rate for 24 hours in patients with septic shock and persistent tachycardia, all while avoiding an increased requirement for vasopressors.," the researchers wrote in Intensive Care Medicine.

Septic shock is a severe condition characterized by a significant drop in blood pressure due to infection, leading to organ dysfunction. Patients often present with persistent tachycardia, making heart rate management a crucial aspect of their treatment. Traditional therapies for controlling heart rate have had mixed results, highlighting the need for effective alternatives.

Against the above background, Sebastian Rehberg, University Hospital of Bielefeld, Bielefeld, Germany, and colleagues examined whether heart rate (HR) control could be achieved without raising the need for vasopressors by using the titratable, highly selective ultra-short-acting β1-blocker landiolol.

For this purpose, the researchers conducted a randomized, open-label, controlled trial across 20 sites in seven European countries from 2018 to 2022. They evaluated the efficacy and safety of landiolol in adult patients experiencing septic shock and persistent tachycardia. Participants were randomly assigned to receive either landiolol combined with standard treatment (n = 99) or standard treatment alone (n = 101).

The primary endpoint focused on achieving a heart rate within the range of 80 to 94 beats per minute and maintaining that rate without increasing the need for vasopressors during the first 24 hours following the start of treatment. Key secondary endpoints included 28-day mortality rates and the occurrence of adverse events.

The findings are summarized as follows:

• The study included a total of 196 septic shock patients, with 98 receiving standard treatment combined with landiolol and 98 receiving standard treatment alone.
• A significantly higher percentage of patients in the landiolol group achieved the combined primary endpoint compared to the control group:
  • Landiolol group: 39.8% (39 out of 98 patients)
  • Control group: 23.5% (23 out of 98 patients)
• The between-group difference in achieving the primary endpoint was 16.5%.
• There were no statistically significant differences between the two groups in secondary outcomes or adverse events.

The study revealed that the ultra-short-acting beta-blocker landiolol effectively reduced and maintained heart rate in patients with septic shock and persistent tachycardia without increasing the need for vasopressors after 24 hours. However, there were no significant differences in adverse events or clinical outcomes, including 28-day mortality, compared to standard care.

"These findings suggest that a strategy focused on strict heart rate reduction to below 95 beats per minute may not be appropriate for all patients with septic shock and persistent tachycardia. Further research is necessary to identify specific patient phenotypes within this population that may clinically benefit from heart rate control," the researchers concluded.

Reference:

Rehberg, S., Frank, S., Černý, V. et al. Landiolol for heart rate control in patients with septic shock and persistent tachycardia. A multicenter randomized clinical trial (Landi-SEP). Intensive Care Med 50, 1622–1634 (2024). https://doi.org/10.1007/s00134-024-07587-1