Systematic review supports etripamil for PSVT treatment

A systemic review presented at AHA 2025 demonstrates the potential of etripamil nasal spray as a patient-administered therapy for paroxysmal supraventricular tachycardia (PSVT), which may reduce reliance on emergency care.

“The management of PSVT episodes often requires visits to a healthcare facility for IV medications or electrical cardioversion, resulting in frequent emergency room (ER) visits, increased healthcare costs, and patient inconvenience,” said the researchers.

Etripamil nasal spray is a self-administered, fast-acting calcium channel blocker under development for the conversion of PSVT outside of a healthcare setting. “Studies have shown the favourable efficacy and safety of etripamil in restoring sinus rhythm (SR) and reducing ER visits,” they said.

This targeted systematic review included phase II–III randomized controlled and open-label trials evaluating etripamil in adults with documental PSVT. The trials were chosen based on their focus on etripamil for termination of acute episodes in patients ≥18 years with a history of PSVT confirmed by electrocardiography. [AHA 2025, abstract Mo3012]

Of the 622 etripamil-exposed patients who experienced PSVT episodes, the Kaplan-Meier (KM) estimate for conversion to SR within 30 mins of administration was 59.6 percent. Across studies, the KM estimates ranged between 53.6 percent and 64.3 percent. The median time to conversion was 18.5 mins.

At 60 mins after drug administration, etripamil conversion rates ranged between 63.2 percent and 75.1 percent across the individual trials.

Safety analysis

In the safety cohort (n=1,279), among participants who have been exposed to etripamil (n=1,056), half had any treatment-emergent adverse events within 24 hours (TEAE24h), but the incidence of serious TEAE24h was low (1 percent).

“The safety profile was favourable and consistent … characterized by predominantly mild, transient, and localized AEs [primarily related to the nasal administration route],” the investigators noted.

About a quarter of etripamil-exposed patients reported nasal discomfort, ~14 percent had nasal congestion, and about 12 percent had rhinorrhoea. Less than 10 percent reported throat irritation and epistaxis.

Test-dose tolerability

To simulate real-world use, 1,107 participants received at least one test dose of etripamil while in SR. In this analysis, there were no clinically significant changes in average baseline heart rate or blood pressure within 45 mins after drug administration.

Only 16 patients (1.4 percent) had test-dose failure, which was defined as intolerance that requires discontinuation, the researchers noted. The test-dose failure was primarily attributed to mild nasal symptoms that quickly resolved. Other reasons for test-dose failure were hypotension and premature ventricular contractions.

“The low rate of test-dose failure among patients in SR further indicates the consistent tolerability of etripamil,” said the researchers.

Self-treatment potential

Etripamil showed consistent efficacy across trial phases, designs, and geographic regions, with the treatment showing greater conversion rates for symptomatic PSVT episodes than placebo, the researchers said.

They added that the safety data and the low rate of test-dose failures denote favourable tolerability, suggesting no need for a pretreatment test dose.

“These findings position etripamil as a potential therapy for PSVT management, potentially empowering patients to self-treat episodes and substantially reducing reliance on emergency healthcare services,” they added. “Future use of etripamil and subsequent research will enable more robust meta-analyses.”