Etripamil Nasal Spray Outperforms Placebo for AFib with Rapid Ventricular Rate

Published on: 

In the phase 2 ReVeRA trial, etripamil nasal spray provided a marked reduction in ventricular rates among patients with atrial fibrillation and rapid ventricular rates.

Results of the phase 2 ReVeRA trial suggest use of etripamil nasal spray was associated with a rapid and statistically significant reduction in ventricular rate among patients with atrial fibrillation and rapid ventricular rate, with results pointing to a 30 beats per minute reduction, relative to placebo, when used for an episode.

Presented at the American Heart Association Scientific Sessions 2023, results of the study provide further insight into the potential role of etripamil nasal spray in the management of arrhythmias as the agent approaches its PDUFA date for the treatment of paroxysmal supraventricular tachycardia (PSVT).1

"Breakthrough episodes of rapid ventricular rate in patients with AFib are frequent and often symptomatic and may result in increasing burdens in patients' everyday lives and disruptions to the healthcare system. Today, there is an unmet need for a portable, fast-acting treatment solution that can be easily administered by patients when they experience a sudden episode," said lead investigator A. John Camm, MD, the British Heart Foundation Emeritus Professor of Clinical Cardiology in The Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute of St. George's University of London.2 "The results presented and published today from the ReVeRA Phase 2 study are encouraging for patients and healthcare providers who are seeking a treatment solution that delivers significant symptom relief and helps reduce potential visits to the emergency department."

A randomized, double-blind, placebo-controlled study conducted in 23 sites in Canada and The Netherlands, ReVeRA was designed to assess the safety and efficacy of etripamil nasal spray relative to placebo for the solution of rapid ventricular rates in patients with atrial fibrillation. For the purpose of analysis, rapid ventricular rate was defined as 110 beats per minute or greater.1

A total of 87 patients underwent screening in the trial. Of these, 69 underwent randomization and 56 received their assigned intervention, with 27 receiving self-administered etripamil nasal spray and 29 receiving. The primary outcome of interest for the trial was the effectiveness of etripamil nasal spray relative to placebo therapy for reducing ventricular rates within 60 minutes of treatment.1

Investigators noted multiple secondary endpoints were incorporated into the study. These included achievement of ventricular rate of less than 100 beats per minute, reduction by 10% or more and 20% or more, relief-of-symptoms, and adverse events as well as additional measures to 360 minutes.1

In analyses adjusted for baseline ventricular rates, results suggested the difference in mean maximum difference over 60 minutes was -29.91 beats per minute in favor of etripamil nasal spray (95% confidence interval, -40.31 to -19.52; P <.0001), with this effect persisting up to 150 minutes. Analysis of secondary endpoints indicated a greater proportion of patients achieved reductions of less than 100 beats per minute, reductions of 10% or greater, and reductions of 20% or greater among the etripamil nasal spray relative to the placebo arm.1

Investigators highlighted ventricular rate reductions of 20% or greater occurred among 66.7% of the etripamil nasal spray arm but did not occur among a single patient receiving placebo. Investigators also highlighted significant improvements in symptom relief and treatment effectiveness, which were assessed using the Treatment Satisfaction Questionnaire for Medication-9, which pointed to significant improvements in both domains for those with etripamil nasal spray compared to placebo. Safety analysis indicated serious adverse events were rare, with a single patient in the etripamil nasal spray arm experiencing transient severe bradycardia and syncope.1

As part of our coverage of AHA 2023, HCPLive Cardiology sat down with ReVeRA investigator James Ip, MD, associate professor of Clinical Medicine and director of Cardiac Pacing and Implantable Devices at Weill Cornell Medicine, for more perspective on the trial and how it might help further inform electrophysiologists and other care providers on the potential of etripamil nasal spray as the agent nears its 2024 PDUFA date for PSVT.

Relevant disclosures for Ip include Milestone Pharmaceuticals.


  1. Camm AJ, Piccini JP, Alings M, et al. A Multicenter, Phase 2, Randomized, Controlled Study of the Efficacy and Safety of Etripamil Nasal Spray for the Acute Reduction of Rapid Ventricular Rate in Patients with Symptomatic Atrial Fibrillation (ReVeRA-201). Circulation: Arrhythmia and Electrophysiology. Published online November 11, 2023. doi:10.1161/CIRCEP.123.012567
  2. Milestone Pharmaceuticals presents positive results from Revera Phase 2 study of etripamil in afib-RVR at the American Heart Association Scientific Sessions 2023. Milestone Pharmaceuticals, Inc. November 11, 2023. Accessed November 11, 2023.