Landiolol Effective for Sepsis-Related Tachyarrhythmias

By Marilynn Larkin

April 14, 2020

NEW YORK (Reuters Health) - The ultra-short-acting beta blocker landiolol safely and effectively treated sepsis-related tachyarrhythmias in its first open-label randomized controlled trial, held in Japan.

Dr. Naoyuki Magsuda of Ngoya University Graduate School of Medicine and colleagues studied intensive care unit patients who received conventional treatment for sepsis and who subsequently developed a tachyarrhythmia.

As reported in The Lancet Respiratory Medicine, 151 were randomly assigned to landiolol or conventional sepsis therapy (control) from 2018-2019. The mean age overall was about 67 (68% male in the landiolol group). The mean heart rate at randomization was 117.5 bpm. Eighty percent had sinus tachycardia and 19%, atrial fibrillation; 91% had septic shock.

The mean dose of landiolol was 5.85 mcg/kg per min at 24 h after enrollment; 4.96 mcg/kg per min at 48 h; 4.12 mcg/kg per min at 72 h; and 4.10 mcg/kg per min at 96 h.

The mean landiolol dose during the study period was 4.15 mcg/kg/min, ranging from 0.17 mcg/kg/min to 19.45 mcg/kg/min. The mean maximum dose was 6.96 mcg/kg/min, and the time to maximum dose was 18.6 h.

A significantly larger proportion of patients given landiolol had a heart rate of 60-94 bpm 24 h after randomization than controls (55% vs. 33%).

Sixty-four percent of patients in the landiolol group and 59% of controls experienced an adverse event, with serious adverse events (including events leading to death) in 12% in the landiolol group and 11% of controls.

Serious adverse events related to landiolol occurred in five (6%): blood pressure decreases in three patients (4%) and cardiac arrest, heart rate decrease, and ejection fraction decrease in one patient each (1%).

The authors note that while landiolol was well tolerated, "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."

Dr. Lior Jankelson, director of the Inherited Arrhythmia Program at NYU Langone Health commented in an email to Reuters Health, "This is an important study showing the potential role of landiolol in controlling the heart rate of patients with sepsis."

However, he noted, "despite better control of heart rate, echocardiographic/hemodynamic data was not reported in the study. It is therefore important to investigate if better heart rate control would translate to improved hemodynamics."

"The study demonstrates an important role (for landiolol) in reducing the incidence of new-onset atrial fibrillation," he said. "The importance of and implications of preventing acute sepsis-related atrial fibrillation should also be investigated in a prospective manner."

"Finally," he added, "the benefits of landiolol over esmolol would have to be proven in a head-to-head trial."

Dr. Davendra Mehta, an electrophysiologist at Mount Sinai Morningside in New York City told Reuters Health by phone, "The findings are promising, but the numbers were relatively small, so we need larger studies."

Like Dr. Jankelson, he noted that the benefits of landiolol over esmolol need to be studied. "The bottom line is that it's too early to change anything in practice," he said. "There are other drugs available right now that do the same thing."

The authors note that clinical trials are underway in the EU (EudraCT 2017-002138-22; and the UK (EudraCT 2017-001785-14;

The study was funded by Ono Pharmaceutical Co. Dr. Magsuda and seven coauthors have received fees from the company and two coauthors are employees.

Dr. Magsuda did not respond to requests for a comment.

SOURCE: and The Lancet Respiratory Medicine, online March 31, 2020.