Self-Administered Nasal Etripamil Restores Sinus Rhythm Safely, With James Ip, MD

Self-administered etripamil nasal spray has demonstrated significant and robust efficacy in restoring sinus rhythm (SR) in patients with acute paroxysmal supraventricular tachycardia (PSVT) outside of a health-care setting, according to a series of clinical trials.1

Presented at the American Heart Association’s Scientific Sessions 2025 in New Orleans, Louisiana, by James Ip, MD, a professor and cardiologist at Weill Cornell Medicine, these data highlight the experimental treatment’s efficacy and tolerability across the NODE-1, NODE-301 Part 1 and 2, NODE-302, and NODE-303 phase 3 clinical studies.1

“The nice thing about etripamil is that it is designed for at-home use,” Ip said in an interview with HCPLive. When patients cannot terminate PSVT, the next step is to go into the ER for an intravenous dose of the medication. And when they get their drugs, some patients can have chest discomfort, shortness of breath, or tiredness; the feeling that their heart stops and pauses for a long period of time. The nice thing about etripamil is that it’s a bit gentler, there are no pauses.”

Etripamil, a fast-acting intranasal calcium-channel blocker, is designed for self-administration to terminate PSVT episodes. A series of previous trials have indicated its safety and efficacy after an initial medically supervised test dose during sinus rhythm.2

The most recent clinical study investigating etripamil, NODE-303, was an event-driven, open-label, single-arm phase 3 study evaluating etripamil for multiple, at-home PSVT episodes without a test dose prior to first use. Investigators included patients with a diagnosis of PSVT by a healthcare professional, a history of PSVT, atrial fibrillation, or atrial flutter, and ≥1 prior episode of sustained PSVT. Patients with a history of second- or third-degree AV block, severe ventricular arrhythmia, symptoms of heart failure Class II-IV, systolic blood pressure <90 mmHg at any study visit, or symptoms of marked hypotension or syncope associated with a PSVT episode were excluded.2

Of the 1116 patients enrolled in NODE-303, 503 treated ≥1 perceived PSVT episode, resulting in a total of 1054 episodes. Adverse events were mild or moderate and localised, with 30.2% of patients experiencing nasal discomfort, 13.9% experiencing nasal congestion, 13.1% experiencing rhinorrhea, and 7.4% experiencing epistaxis. Investigators ultimately concluded that etripamil was well-tolerated when self-administered in a real-world setting.2

Ip and colleagues collected data from NODE-303 and previous similar trials for the current study. When examining efficacy data, the team included the proportion of patients converting from PSVT to SR within 30 minutes of treatment administration and the median times to conversion across all studies. The Kaplan-Meier estimate of etripamil found that 59.6% of patients who had administered treatment converted to SR within 30 minutes (n = 662; range, 53.6%-64.3%), with a median time to conversion of 18.5 minutes (95% CI, 15.7-21). The proportions of placebo patients between all trials converting from SVT to SR by 30 minutes ranged from 26.7% to 34.7%.1

The combined analysis also showed the occurrence of primarily mild, transient treatment treatment-emergent adverse events, which included the same lineup as NODE-303. Of the overall number of included patients, 1107 took ≥1 etripamil test dose while in SR, after which no significant change in average baseline heart rate or blood pressure was observed within 45 minutes. A test dose failure only occurred in 1.4% of patients (n = 16).1

Ultimately, Ip and colleagues interpreted these results as indicative of the safety and tolerability of etripamil for PSVT management. They noted that the self-administration model may also effectively reduce patient reliance on emergency care.1

“Many patients who have PSVT, they get the medication, and within a few minutes they have another recording showing normal rhythm,” Ip said. “I’m very excited that this is something that’s going to empower patients to use wearables, or a smart watch, some device to confirm that they are having the episode, and then give the medication, confirm it’s gone, and then stay at home.”

References

1. Ip J, Noseworthy P, Piccini J, et al. Combined Efficacy, Safety, and Test Dose Tolerability of Etripamil for Acute Paroxysmal Supraventricular Tachycardia (PSVT) Across Multiple Clinical Trials. Presented at the American Heart Association’s Scientific Sessions 2025. New Orleans, Louisiana. November 8-10, 2025.

2. Ip JE, Coutu B, Ip JH, et al. Etripamil Nasal Spray for Recurrent Paroxysmal Supraventricular Tachycardia Conversion: Results From the NODE-303 Open-Label Study. J Cardiovasc Electrophysiol. 2025;36(11):2990-3003. doi:10.1111/jce.70086