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).

Autor:	Camm AJ; Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St. George's University of London, United Kingdom (A.J.C.)., Piccini JP; Duke University Medical Center and Duke Clinical Research Institute, Durham, NC (J.P.P.)., Alings M; Department of Cardiology, Amphie Hospital, Breda, the Netherlands (M.A.)., Dorian P; Division of Cardiology, Unity Health Toronto, Ontario, Canada (P.D.)., Gosselin G; Department of Medicine, Montreal Heart Institute, Québec, Canada (G.G., M.-C.G., B.M., D.R.)., Guertin MC; Department of Medicine, Montreal Heart Institute, Québec, Canada (G.G., M.-C.G., B.M., D.R.)., Ip JE; Division of Cardiology, Department of Medicine, Weill Cornell Medicine, New York Presbyterian Hospital (J.E.I.)., Kowey PR; Cardiology Division and Lankenau Institute for Medical Research, Lankenau Medical Center, Wynnewood, PA (P.R.K.)., Mondésert B; Department of Medicine, Montreal Heart Institute, Québec, Canada (G.G., M.-C.G., B.M., D.R.)., Prins FJ; Elkerliek, Helmond, the Netherlands (F.J.P.)., Roux JF; Centre Hospitalier de l'Université de Sherbrooke, Québec, Canada (J.-F.R.)., Stambler BS; Piedmont Heart Institute, Atlanta, GA (B.S.S.)., van Eck J; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands (J.W.M.v.E.)., Al Windy N; Gelre Ziekenhuizen, Zutphen, the Netherlands (N.A.W.)., Thermil N; Milestone Pharmaceuticals, Montreal, Canada (N.T., S.S.)., Shardonofsky S; Milestone Pharmaceuticals, Montreal, Canada (N.T., S.S.)., Bharucha DB; Milestone Pharmaceuticals, Charlotte, NC (D.B.B.)., Roy D; Department of Medicine, Montreal Heart Institute, Québec, Canada (G.G., M.-C.G., B.M., D.R.).
Jazyk:	angličtina
Zdroj:	Circulation. Arrhythmia and electrophysiology [Circ Arrhythm Electrophysiol] 2023 Dec; Vol. 16 (12), pp. 639-650. Date of Electronic Publication: 2023 Nov 11.
DOI:	10.1161/CIRCEP.123.012567
Abstrakt:	Background: Despite chronic therapies, atrial fibrillation (AF) leads to rapid ventricular rates (RVR) often requiring intravenous treatments. Etripamil is a fast-acting, calcium-channel blocker administered intranasally affecting the atrioventricular node within minutes. Methods: Reduction of Ventricular Rate in Patients with Atrial Fibrillation evaluated the efficacy and safety of etripamil for the reduction of ventricular rate (VR) in patients presenting urgently with AF-RVR (VR ≥110 beats per minute [bpm]), was randomized, double-blind, placebo-controlled, and conducted in Canada and the Netherlands. Patients presenting urgently with AF-RVR were randomized (1:1, etripamil nasal spray 70 mg: placebo nasal spray). The primary objective was to demonstrate the effectiveness of etripamil in reducing VR in AF-RVR within 60 minutes of treatment. Secondary objectives assessed achievement of VR <100 bpm, reduction by ≥10% and ≥20%, relief of symptoms and treatment effectiveness; adverse events; and additional measures to 360 minutes. Results: Sixty-nine patients were randomized, 56 dosed with etripamil (n=27) or placebo (n=29). The median age was 65 years; 39% were female patients; proportions of AF types were similar between groups. The difference of mean maximum reductions in VR over 60 minutes, etripamil versus placebo, adjusting for baseline VR, was -29.91 bpm (95% CI, -40.31 to -19.52; P <0.0001). VR reductions persisted up to 150 minutes. Significantly greater proportions of patients receiving etripamil achieved VR reductions <100 bpm (with longer median duration <100 bpm), or VR reduction by ≥10% or ≥20%, versus placebo. VR reduction ≥20% occurred in 66.7% of patients in the etripamil arm and no patients in placebo. Using the Treatment Satisfaction Questionnaire for Medication-9, there was significant improvement in satisfaction on symptom relief and treatment effectiveness with etripamil versus placebo. Serious adverse events were rare; 1 patient in the etripamil arm experienced transient severe bradycardia and syncope, assessed as due to hypervagotonia. Conclusions: Intranasal etripamil 70 mg reduced VR and improved symptom relief and treatment satisfaction. These data support further development of self-administered etripamil for the treatment of AF-RVR. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04467905. Competing Interests: Disclosures Dr Camm has received grants and personal fees from Boehringer Ingelheim, Bayer, Pfizer, Bristol-Myers Squibb, and Daiichi Sankyo; personal fees from Medtronic, Boston Scientific, Menarini, and Biotronik; and support from Anthos, Sanofi, Abbott, GlaxoSmithKline, and Johnson & Johnson. Dr Piccini has received grants for clinical research from Abbott, the American Heart Association, the Association for the Advancement of Medical Instrumentation, Bayer, Boston Scientific, iRhythm, and Philips and serves as a consultant to Abbott, AbbVie, ARCA biopharma, Bayer, Boston Scientific, Bristol-Myers Squibb (Myokardia), Element Science, Itamar Medical, LivaNova, Medtronic, ElectroPhysiology Frontiers, ReCor, Sanofi, Philips, and UpToDate. Dr Alings has no disclosures to report. Drs Dorian, Ip, and Stambler serve on the steering committee for Milestone Pharmaceuticals. Dr Gosselin has no disclosures to report. Drs Kowey and Mondésert are consultants for Milestone Pharmaceuticals. Drs Prins, Roux, van Eck, and Al Windy have no disclosures to report. Drs Thermil, Shardonofsky, and Bharucha are employees of Milestone Pharmaceuticals. Dr Roy has no disclosures to report.
Databáze:	MEDLINE
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