A newly published randomized control trial, highlighting the efficacy and safety of landiolol in sepsis-related tachyarrhythmia, has shown promise. The ultra-short acting β1-selective antagonist was successful in reducing the incidence of new-onset arrhythmia. The trial, published on March 31st, 2020, was funded by Ono Pharmaceuticals and completed in Japan.
Background
Sepsis has been a thorn in the side of many institutions, with annual rates estimated around 1,665,000 between 1979 and 2000. From 2005 to 2014, an analysis of 27 hospitals found an increase of septic shock from 12.8 to 18.6 per 1000 hospital admissions. Sepsis itself exists on a continuum of ranging conditions. From infection and bacteremia to septic shock, ultimately leading to organ dysfunction and death.
Sepsis is a syndrome characterized by systemic inflammation as a result of infection. When sepsis is suspected, patients tend to present with a combination of symptoms. Those symptoms range from hypotension and tachycardia to fever and leukocytosis. As severity worsens, shock and organ dysfunction can present, ultimately leading to death. When tachycardia becomes significant, it can lead to fast atrial fibrillation. The need to treat the tachyarrhythmias becomes important but many treatment options can be ineffective.
Trials
The trial evaluating Landiolol, which was published in The Lancet Respiratory Medicine, was done at 54 hospitals in Japan. Patients were randomized to either Landiolol or a control group. Both groups received conventional therapy, coinciding with the Japanese clinical guidelines for managing sepsis. That conventional therapy consists of respiratory and fluid resuscitation, antimicrobials, and catecholamines.
It was found that a significantly larger proportion of patients in the landiolol arm achieved a heart rate of 60–94 bpm in 24 hours after the randomization than compared to the control group. Statistically, 55% in the landiolol group vs. 33% in the control group. While these results do show promise with the use of landiolol, the study reported increased adverse events pertaining to the landiolol group. 64% of the patients in the landiolol group presented with adverse events with serious adverse events, including death, occurring in 12%. Adverse events directly related to landiolol use occurring in 6% of patients.
Outcomes
In the end, Landiolol resulted in more patients with sepsis-related tachyarrhythmia getting to a heart rate of 60–94 bpm at 24 hours, significantly reducing the incidence of new-onset arrhythmia. However, the trial authors stated that:
“it should be used under appropriate monitoring of blood pressure and heart rate owing to the risk of hypotension in patients with sepsis and septic shock”.
Reuters Health recently reached out to Dr. Lior Jankelson, who is the director of the Inherited Arrhythmia Program, and he noted that the trial lacked data on echocardiography. He later goes on to say that:
“It is therefore important to investigate if better heart rate control would translate to improved hemodynamics”.
Conclusion
Landiolol has shown that it could potentially play an important role in sepsis-related tachyarrhythmias. Landiolol still has further investigating to be done if it seeks to become an integrated part of the treatment strategy. If landiolol can present more studies boasting its effectiveness, its next step should aim at gaining an FDA approval, and branching outside of Europe and Japan.
Thank you for reading,
Aaron Forsythe LECOM School of Pharmacy
References
Efficacy and safety of landiolol, an ultra-short-acting β1-selective antagonist, for treatment of sepsis-related tachyarrhythmia (J-Land 3S): a multicentre, open-label, randomised controlled trial
Kakihana Y., et al. “Efficacy and safety of landiolol, an ultra-short-acting β1-selective antagonist, for treatment of sepsis-related tachyarrhythmia (J-Land 3S): a multicentre, open-label, randomised controlled trial.” The Lancet Respiratory Medicine, 31 Mar. 2020, https://www-sciencedirect-com.lecomlrc.lecom.edu/science/article/abs/pii/S2213260020300370?via%3Dihub.
“Landiolol Effective for Sepsis-Related Tachyarrhythmias.” Medscape, 14 Apr. 2020, www.medscape.com/viewarticle/928595.
Schmidt, GA. Evaluation and management of suspected sepsis and septic shock in adults. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, 2020.
