{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:49:43Z","timestamp":1783608583845,"version":"3.55.0"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Milestone Pharmaceuticals"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>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 \u2265110 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 &lt;100 bpm, reduction by \u226510% and \u226520%, relief of symptoms and treatment effectiveness; adverse events; and additional measures to 360 minutes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>\n              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 \u221229.91 bpm (95% CI, \u221240.31 to \u221219.52;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001). VR reductions persisted up to 150 minutes. Significantly greater proportions of patients receiving etripamil achieved VR reductions &lt;100 bpm (with longer median duration &lt;100 bpm), or VR reduction by \u226510% or \u226520%, versus placebo. VR reduction \u226520% 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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>REGISTRATION:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique Identifier: NCT04467905\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.123.012567","type":"journal-article","created":{"date-parts":[[2023,11,11]],"date-time":"2023-11-11T15:00:10Z","timestamp":1699714810000},"page":"639-650","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["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)"],"prefix":"10.1161","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct04467905","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2536-2871","authenticated-orcid":true,"given":"A. John","family":"Camm","sequence":"first","affiliation":[{"name":"Cardiology Clinical Academic Group, Molecular and Clinical Sciences Research Institute, St. George\u2019s University of London, United Kingdom (A.J.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0772-2404","authenticated-orcid":true,"given":"Jonathan P.","family":"Piccini","sequence":"additional","affiliation":[{"name":"Duke University Medical Center and Duke Clinical Research Institute, Durham, NC (J.P.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2090-4683","authenticated-orcid":true,"given":"Marco","family":"Alings","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Amphie Hospital, Breda, the Netherlands (M.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8244-3520","authenticated-orcid":true,"given":"Paul","family":"Dorian","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Unity Health Toronto, Ontario, Canada (P.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3921-5909","authenticated-orcid":true,"given":"Gilbert","family":"Gosselin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Montreal Heart Institute, Qu\u00e9bec, Canada (G.G., M.-C.G., B.M., D.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8523-5148","authenticated-orcid":true,"given":"Marie-Claude","family":"Guertin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Montreal Heart Institute, Qu\u00e9bec, Canada (G.G., M.-C.G., B.M., D.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3461-505X","authenticated-orcid":true,"given":"James E.","family":"Ip","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine, Weill Cornell Medicine, New York Presbyterian Hospital (J.E.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7189-1638","authenticated-orcid":true,"given":"Peter R.","family":"Kowey","sequence":"additional","affiliation":[{"name":"Cardiology Division and Lankenau Institute for Medical Research, Lankenau Medical Center, Wynnewood, PA (P.R.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7777-5689","authenticated-orcid":true,"given":"Blandine","family":"Mond\u00e9sert","sequence":"additional","affiliation":[{"name":"Department of Medicine, Montreal Heart Institute, Qu\u00e9bec, Canada (G.G., M.-C.G., B.M., 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