PracticeUpdate: Cardiology - Winter 2018

EDITOR’S PICKS 7

Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia to Sinus Rhythm JACC: Journal of the American College of Cardiology

with etripamil was <3 min. Adverse events were mostly related to the intranasal route of admin- istration or local irritation. Reductions in blood pressure occurred predominantly in the highest etripamil dose. CONCLUSIONS Etripamil nasal spray rapidly termi- nated induced SVT with a high conversion rate. The safety and efficacy results of this study pro- vide guidance for etripamil dose selection for future studies involving self-administration of this new intranasal calcium-channel blocker in a real-world setting for the termination of SVT. Etripamil Nasal Spray for Rapid Conversion of Supraventricular Tachycardia to Sinus Rhythm. J Am Coll Cardiol 2018 Jul 31;72(5)489-497, BS Stambler, P Dorian, PT Sager, et al. www.practiceupdate.com/c/71370 still need to be verified in phase III controlled studies conducted outside of the electrophysiology laboratory in non-sedated patients. " " …its safety and efficacy

Take-home message • In this phase II study, 104 patients with paroxysmal supraventricular tachycardia were given etripamil to determine its safety and efficacy. Patients who received etripamil nasal spray exhibited between 65% and 95% conversion from supraventricular tachycardia to sinus rhythm, compared with 35% in the placebo group. Median time to conversion was less than 3 minutes with etripamil. Frequently reported adverse events included local irritation or reduced blood pressure with the highest dose. • These results support further study investigating self-administration of etripamil in a real-world setting. Abstract

BACKGROUND There is no nonparenteral medi- cation for the rapid termination of paroxysmal supraventricular tachycardia. OBJECTIVES The purpose of this study was to assess the efficacy and safety of etripamil nasal spray, a short-acting calcium-channel blocker, for the rapid termination of paroxysmal supraven- tricular tachycardia (SVT). METHODS This phase 2 study was performed during electrophysiological testing in patients with previously documented SVT who were induced into SVT prior to undergoing a cathe- ter ablation. Patients in sustained SVT for 5 min

received either placebo or 1 of 4 doses of active compound. The primary endpoint was the SVT conversion rate within 15 min of study drug administration. Secondary endpoints included time to conversion and adverse events. RESULTS One hundred four patients were dosed. Conversion rates from SVT to sinus rhythm were between 65% and 95% in the etripamil nasal spray groups and 35% in the placebo group; the differences were statistically significant (Pearson chi-square test) in the 3 highest active com- pound dose groups versus placebo. In patients who converted, the median time to conversion

COMMENT By Ziad F. Issa MD, MMM C atheter ablation is the treatment of choice in patients with paroxysmal supraventricular tachycardia (SVT) who desire to avoid or are unresponsive or intolerant to drug therapy. For patients requiring therapy who are reluctant to undergo cath- eter ablation, drug therapy remains a viable alternative, although with significantly lower efficacy rates. For patients with frequent episodes of SVT, chronic prophylactic therapy is recommended. Selected patients with very infrequent, well tolerated episodes of paroxysmal SVT may be treated only for acute episodes. For acute conversion of SVT, vagal maneuvers (including Val- salva and carotid sinus massage) are the first-line intervention, though their success rate remains limited (<30%). When vagal maneuvers fail, outpatients may use a single oral dose to acutely terminate an episode of SVT. This so-called “pill in the pocket” approach necessitates the use of a drug that has a short onset of action (ie, immediate-release preparations), and currently, no such drugs are available for nonparenteral self-administration. Although oral verapamil, diltiazem, beta-blockers, and flecainide have been utilized in these situations, their onset of action is relatively slow and their efficacy is modest. Therefore, in many patients with sustained SVT, acute termination of the arrhythmia often requires intravenous drug therapy in a controlled medical environment.

The study by Stambler et al examined the efficacy of different doses of intranasal etripamil (a rapid-onset, short-acting, pheny- lalkylamine class L-type calcium-channel blocker) in terminating sustained (>5 minutes) SVT induced in the electrophysiology laboratory. The drug demonstrated high efficacy for rapid termi- nation (within 15 min) of SVT compared with placebo. The median time to conversion from SVT to sinus rhythm was <3 min. Atrio- ventricular nodal reentry was the mechanism of the SVT in the vast majority of study patients. Although a self-administered etripamil nasal spray can poten- tially become an important approach for the acute management of SVT, its safety and efficacy still need to be verified in phase III controlled studies conducted outside of the electrophysiology laboratory in non-sedated patients. Additionally, whether study findings can be extended to patients with longer durations of sustained SVT and those with other SVT mechanisms is yet to be evaluated.

Dr. Issa is Executive Director of Cardiac Electrophysiology at Prairie Heart Institute of Illinois, and Medical Director of Cardiac Electrophysiology Laboratory at HSHS St. John’s Hospital in Springfield, Illinois.

VOL. 3 • NO. 3 • 2018