Ivabradine for chronic heart rate control in persistent atrial fibrillation. Design of the BRAKE-AF project
Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRA...
Gespeichert in:
| Veröffentlicht in: | Revista española de cardiología (English ed.) 2020-05, Vol.73 (5), p.368-375 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 375 |
|---|---|
| container_issue | 5 |
| container_start_page | 368 |
| container_title | Revista española de cardiología (English ed.) |
| container_volume | 73 |
| creator | Fontenla, Adolfo López-Gil, María Tamargo-Menéndez, Juan Matía-Francés, Roberto Salgado-Aranda, Ricardo Rey-Blas, Juan Ramón Miracle-Blanco, Ángel Mejía-Martínez, Elena Pastor-Fuentes, Agustín Toquero-Ramos, Jorge Arias, Miguel Ángel Montilla, Isabel Gómez de la Cámara, Agustín Arribas, Fernando |
| description | Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF).
A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques.
New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF.
The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF.
Clinical trial registration: http://www.clinicaltrials.gov. Identifier: NCT03718273.
La ivabradina es un inhibidor de la corriente If, principal determinante de la función marcapasos del nódulo sinusal, aprobado como antianginoso y para tratar la insuficiencia cardiaca. Existen indicios sobre su capacidad para inhibir la conducción a través del nódulo auriculoventricular (NAV). Sobre esta base, el proyecto BRAKE-AF plantea el uso de ivabradina como agente cronotrópico negativo en fibrilación auricular (FA).
Se realizará un ensayo clínico multicéntrico de fase III, aleatorizado, abierto, en paralelo, con diseño de no inferioridad, para comparar la ivabradina frente a la digoxina en 232 pacientes con FA permanente no controlada con bloqueadores beta o antagonistas del calcio; el objetivo primario es la reducción de la frecuencia cardiaca media diurna en un Holter de 24h a los 3 meses. El ensayo se apoyará en un estudio electrofisiológico que analizará el efecto de la ivabradina en el potencial de acción del NAV humano, utilizando un modelo experimental en células de ov |
| doi_str_mv | 10.1016/j.rec.2019.09.004 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2307394861</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1885585719302877</els_id><sourcerecordid>2307394861</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1988-5ba1db5d53e4aa1bac9ba4b108f0ef4e80520eddc3437d507bcdfca727e2639e3</originalsourceid><addsrcrecordid>eNp9kE9vFDEMxSMEoqXwAbigHLnM4EySnYw4LaWFqpWQqnKO8sfDZplNliRbiW9Pqi2IUyVL9uG9Z_tHyFsGPQO2-rDtM7p-ADb10ArEM3LKlJKdVHJ8_t98Ql6VsgWQXI3iJTnhbMUZCHVKfl7dG5uNDxHpnDJ1m5xicHSDJleaTUXqUqw5LTREusdcQqkYKzU1B7PQOdgclsXUkGJPP2MJPyJNM60bpJ9u19cX3fqS7nPaoquvyYvZLAXfPPYz8v3y4u78a3fz7cvV-fqmc2xSqpPWMG-llxyFMcwaN1kjLAM1A84CFcgB0HvHBR-9hNE6PzszDiMOKz4hPyPvj7lt768Dlqp3oThsV0ZMh6IHDiOfhFqxJmVHqcuplIyz3uewM_m3ZqAfGOutboz1A2MNrUA0z7vH-IPdof_n-Au1CT4eBdievA-YdXEBo0MfWlbVPoUn4v8AcLGNlg</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2307394861</pqid></control><display><type>article</type><title>Ivabradine for chronic heart rate control in persistent atrial fibrillation. Design of the BRAKE-AF project</title><source>MEDLINE</source><source>Elsevier ScienceDirect Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Fontenla, Adolfo ; López-Gil, María ; Tamargo-Menéndez, Juan ; Matía-Francés, Roberto ; Salgado-Aranda, Ricardo ; Rey-Blas, Juan Ramón ; Miracle-Blanco, Ángel ; Mejía-Martínez, Elena ; Pastor-Fuentes, Agustín ; Toquero-Ramos, Jorge ; Arias, Miguel Ángel ; Montilla, Isabel ; Gómez de la Cámara, Agustín ; Arribas, Fernando</creator><creatorcontrib>Fontenla, Adolfo ; López-Gil, María ; Tamargo-Menéndez, Juan ; Matía-Francés, Roberto ; Salgado-Aranda, Ricardo ; Rey-Blas, Juan Ramón ; Miracle-Blanco, Ángel ; Mejía-Martínez, Elena ; Pastor-Fuentes, Agustín ; Toquero-Ramos, Jorge ; Arias, Miguel Ángel ; Montilla, Isabel ; Gómez de la Cámara, Agustín ; Arribas, Fernando ; on behalf of the BRAKE-AF investigators ; BRAKE-AF investigators</creatorcontrib><description>Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF).
A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques.
New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF.
The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF.
Clinical trial registration: http://www.clinicaltrials.gov. Identifier: NCT03718273.
La ivabradina es un inhibidor de la corriente If, principal determinante de la función marcapasos del nódulo sinusal, aprobado como antianginoso y para tratar la insuficiencia cardiaca. Existen indicios sobre su capacidad para inhibir la conducción a través del nódulo auriculoventricular (NAV). Sobre esta base, el proyecto BRAKE-AF plantea el uso de ivabradina como agente cronotrópico negativo en fibrilación auricular (FA).
Se realizará un ensayo clínico multicéntrico de fase III, aleatorizado, abierto, en paralelo, con diseño de no inferioridad, para comparar la ivabradina frente a la digoxina en 232 pacientes con FA permanente no controlada con bloqueadores beta o antagonistas del calcio; el objetivo primario es la reducción de la frecuencia cardiaca media diurna en un Holter de 24h a los 3 meses. El ensayo se apoyará en un estudio electrofisiológico que analizará el efecto de la ivabradina en el potencial de acción del NAV humano, utilizando un modelo experimental en células de ovario de hámster chino transfectadas con el ADN que codifica la expresión de los distintos canales que componen dicho potencial de acción, registrando las corrientes iónicas mediante la técnica del parche de membrana.
Se obtendrá información tanto del efecto de la ivabradina en las corrientes iónicas y el potencial de acción del NAV como de su eficacia y su seguridad en pacientes con FA permanente.
Los resultados del proyecto BRAKE-AF podrían permitir que la ivabradina se incluyera en el limitado arsenal de fármacos disponibles actualmente para el control de frecuencia en la FA.
Ensayo registrado en ClinicalTrials.gov (Identificador: NCT03718273)</description><identifier>ISSN: 1885-5857</identifier><identifier>EISSN: 1885-5857</identifier><identifier>DOI: 10.1016/j.rec.2019.09.004</identifier><identifier>PMID: 31631048</identifier><language>eng</language><publisher>Spain: Elsevier España, S.L.U</publisher><subject>Action potential ; Anti-Arrhythmia Agents - therapeutic use ; Atrial Fibrillation - drug therapy ; Atrioventricular node ; Cardiovascular Agents - therapeutic use ; Control de frecuencia ; Digoxin ; Digoxin - therapeutic use ; Digoxina ; Equivalence Trials as Topic ; Fibrilación auricular permanente ; Heart Rate - drug effects ; Heart Rate - physiology ; Humans ; Ivabradina ; Ivabradine ; Ivabradine - therapeutic use ; Nódulo auriculoventricular ; Parche de membrana ; Patch clamp ; Persistent atrial fibrillation ; Potencial de acción ; Rate control ; Treatment Outcome</subject><ispartof>Revista española de cardiología (English ed.), 2020-05, Vol.73 (5), p.368-375</ispartof><rights>2019 Sociedad Española de Cardiología</rights><rights>Copyright © 2019 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c1988-5ba1db5d53e4aa1bac9ba4b108f0ef4e80520eddc3437d507bcdfca727e2639e3</citedby><cites>FETCH-LOGICAL-c1988-5ba1db5d53e4aa1bac9ba4b108f0ef4e80520eddc3437d507bcdfca727e2639e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1885585719302877$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31631048$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fontenla, Adolfo</creatorcontrib><creatorcontrib>López-Gil, María</creatorcontrib><creatorcontrib>Tamargo-Menéndez, Juan</creatorcontrib><creatorcontrib>Matía-Francés, Roberto</creatorcontrib><creatorcontrib>Salgado-Aranda, Ricardo</creatorcontrib><creatorcontrib>Rey-Blas, Juan Ramón</creatorcontrib><creatorcontrib>Miracle-Blanco, Ángel</creatorcontrib><creatorcontrib>Mejía-Martínez, Elena</creatorcontrib><creatorcontrib>Pastor-Fuentes, Agustín</creatorcontrib><creatorcontrib>Toquero-Ramos, Jorge</creatorcontrib><creatorcontrib>Arias, Miguel Ángel</creatorcontrib><creatorcontrib>Montilla, Isabel</creatorcontrib><creatorcontrib>Gómez de la Cámara, Agustín</creatorcontrib><creatorcontrib>Arribas, Fernando</creatorcontrib><creatorcontrib>on behalf of the BRAKE-AF investigators</creatorcontrib><creatorcontrib>BRAKE-AF investigators</creatorcontrib><title>Ivabradine for chronic heart rate control in persistent atrial fibrillation. Design of the BRAKE-AF project</title><title>Revista española de cardiología (English ed.)</title><addtitle>Rev Esp Cardiol (Engl Ed)</addtitle><description>Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF).
A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques.
New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF.
The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF.
Clinical trial registration: http://www.clinicaltrials.gov. Identifier: NCT03718273.
La ivabradina es un inhibidor de la corriente If, principal determinante de la función marcapasos del nódulo sinusal, aprobado como antianginoso y para tratar la insuficiencia cardiaca. Existen indicios sobre su capacidad para inhibir la conducción a través del nódulo auriculoventricular (NAV). Sobre esta base, el proyecto BRAKE-AF plantea el uso de ivabradina como agente cronotrópico negativo en fibrilación auricular (FA).
Se realizará un ensayo clínico multicéntrico de fase III, aleatorizado, abierto, en paralelo, con diseño de no inferioridad, para comparar la ivabradina frente a la digoxina en 232 pacientes con FA permanente no controlada con bloqueadores beta o antagonistas del calcio; el objetivo primario es la reducción de la frecuencia cardiaca media diurna en un Holter de 24h a los 3 meses. El ensayo se apoyará en un estudio electrofisiológico que analizará el efecto de la ivabradina en el potencial de acción del NAV humano, utilizando un modelo experimental en células de ovario de hámster chino transfectadas con el ADN que codifica la expresión de los distintos canales que componen dicho potencial de acción, registrando las corrientes iónicas mediante la técnica del parche de membrana.
Se obtendrá información tanto del efecto de la ivabradina en las corrientes iónicas y el potencial de acción del NAV como de su eficacia y su seguridad en pacientes con FA permanente.
Los resultados del proyecto BRAKE-AF podrían permitir que la ivabradina se incluyera en el limitado arsenal de fármacos disponibles actualmente para el control de frecuencia en la FA.
Ensayo registrado en ClinicalTrials.gov (Identificador: NCT03718273)</description><subject>Action potential</subject><subject>Anti-Arrhythmia Agents - therapeutic use</subject><subject>Atrial Fibrillation - drug therapy</subject><subject>Atrioventricular node</subject><subject>Cardiovascular Agents - therapeutic use</subject><subject>Control de frecuencia</subject><subject>Digoxin</subject><subject>Digoxin - therapeutic use</subject><subject>Digoxina</subject><subject>Equivalence Trials as Topic</subject><subject>Fibrilación auricular permanente</subject><subject>Heart Rate - drug effects</subject><subject>Heart Rate - physiology</subject><subject>Humans</subject><subject>Ivabradina</subject><subject>Ivabradine</subject><subject>Ivabradine - therapeutic use</subject><subject>Nódulo auriculoventricular</subject><subject>Parche de membrana</subject><subject>Patch clamp</subject><subject>Persistent atrial fibrillation</subject><subject>Potencial de acción</subject><subject>Rate control</subject><subject>Treatment Outcome</subject><issn>1885-5857</issn><issn>1885-5857</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9vFDEMxSMEoqXwAbigHLnM4EySnYw4LaWFqpWQqnKO8sfDZplNliRbiW9Pqi2IUyVL9uG9Z_tHyFsGPQO2-rDtM7p-ADb10ArEM3LKlJKdVHJ8_t98Ql6VsgWQXI3iJTnhbMUZCHVKfl7dG5uNDxHpnDJ1m5xicHSDJleaTUXqUqw5LTREusdcQqkYKzU1B7PQOdgclsXUkGJPP2MJPyJNM60bpJ9u19cX3fqS7nPaoquvyYvZLAXfPPYz8v3y4u78a3fz7cvV-fqmc2xSqpPWMG-llxyFMcwaN1kjLAM1A84CFcgB0HvHBR-9hNE6PzszDiMOKz4hPyPvj7lt768Dlqp3oThsV0ZMh6IHDiOfhFqxJmVHqcuplIyz3uewM_m3ZqAfGOutboz1A2MNrUA0z7vH-IPdof_n-Au1CT4eBdievA-YdXEBo0MfWlbVPoUn4v8AcLGNlg</recordid><startdate>202005</startdate><enddate>202005</enddate><creator>Fontenla, Adolfo</creator><creator>López-Gil, María</creator><creator>Tamargo-Menéndez, Juan</creator><creator>Matía-Francés, Roberto</creator><creator>Salgado-Aranda, Ricardo</creator><creator>Rey-Blas, Juan Ramón</creator><creator>Miracle-Blanco, Ángel</creator><creator>Mejía-Martínez, Elena</creator><creator>Pastor-Fuentes, Agustín</creator><creator>Toquero-Ramos, Jorge</creator><creator>Arias, Miguel Ángel</creator><creator>Montilla, Isabel</creator><creator>Gómez de la Cámara, Agustín</creator><creator>Arribas, Fernando</creator><general>Elsevier España, S.L.U</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>202005</creationdate><title>Ivabradine for chronic heart rate control in persistent atrial fibrillation. Design of the BRAKE-AF project</title><author>Fontenla, Adolfo ; López-Gil, María ; Tamargo-Menéndez, Juan ; Matía-Francés, Roberto ; Salgado-Aranda, Ricardo ; Rey-Blas, Juan Ramón ; Miracle-Blanco, Ángel ; Mejía-Martínez, Elena ; Pastor-Fuentes, Agustín ; Toquero-Ramos, Jorge ; Arias, Miguel Ángel ; Montilla, Isabel ; Gómez de la Cámara, Agustín ; Arribas, Fernando</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c1988-5ba1db5d53e4aa1bac9ba4b108f0ef4e80520eddc3437d507bcdfca727e2639e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Action potential</topic><topic>Anti-Arrhythmia Agents - therapeutic use</topic><topic>Atrial Fibrillation - drug therapy</topic><topic>Atrioventricular node</topic><topic>Cardiovascular Agents - therapeutic use</topic><topic>Control de frecuencia</topic><topic>Digoxin</topic><topic>Digoxin - therapeutic use</topic><topic>Digoxina</topic><topic>Equivalence Trials as Topic</topic><topic>Fibrilación auricular permanente</topic><topic>Heart Rate - drug effects</topic><topic>Heart Rate - physiology</topic><topic>Humans</topic><topic>Ivabradina</topic><topic>Ivabradine</topic><topic>Ivabradine - therapeutic use</topic><topic>Nódulo auriculoventricular</topic><topic>Parche de membrana</topic><topic>Patch clamp</topic><topic>Persistent atrial fibrillation</topic><topic>Potencial de acción</topic><topic>Rate control</topic><topic>Treatment Outcome</topic><toplevel>online_resources</toplevel><creatorcontrib>Fontenla, Adolfo</creatorcontrib><creatorcontrib>López-Gil, María</creatorcontrib><creatorcontrib>Tamargo-Menéndez, Juan</creatorcontrib><creatorcontrib>Matía-Francés, Roberto</creatorcontrib><creatorcontrib>Salgado-Aranda, Ricardo</creatorcontrib><creatorcontrib>Rey-Blas, Juan Ramón</creatorcontrib><creatorcontrib>Miracle-Blanco, Ángel</creatorcontrib><creatorcontrib>Mejía-Martínez, Elena</creatorcontrib><creatorcontrib>Pastor-Fuentes, Agustín</creatorcontrib><creatorcontrib>Toquero-Ramos, Jorge</creatorcontrib><creatorcontrib>Arias, Miguel Ángel</creatorcontrib><creatorcontrib>Montilla, Isabel</creatorcontrib><creatorcontrib>Gómez de la Cámara, Agustín</creatorcontrib><creatorcontrib>Arribas, Fernando</creatorcontrib><creatorcontrib>on behalf of the BRAKE-AF investigators</creatorcontrib><creatorcontrib>BRAKE-AF investigators</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Revista española de cardiología (English ed.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fontenla, Adolfo</au><au>López-Gil, María</au><au>Tamargo-Menéndez, Juan</au><au>Matía-Francés, Roberto</au><au>Salgado-Aranda, Ricardo</au><au>Rey-Blas, Juan Ramón</au><au>Miracle-Blanco, Ángel</au><au>Mejía-Martínez, Elena</au><au>Pastor-Fuentes, Agustín</au><au>Toquero-Ramos, Jorge</au><au>Arias, Miguel Ángel</au><au>Montilla, Isabel</au><au>Gómez de la Cámara, Agustín</au><au>Arribas, Fernando</au><aucorp>on behalf of the BRAKE-AF investigators</aucorp><aucorp>BRAKE-AF investigators</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ivabradine for chronic heart rate control in persistent atrial fibrillation. Design of the BRAKE-AF project</atitle><jtitle>Revista española de cardiología (English ed.)</jtitle><addtitle>Rev Esp Cardiol (Engl Ed)</addtitle><date>2020-05</date><risdate>2020</risdate><volume>73</volume><issue>5</issue><spage>368</spage><epage>375</epage><pages>368-375</pages><issn>1885-5857</issn><eissn>1885-5857</eissn><abstract>Ivabradine is an inhibitor of the If channel, the main determinant of the pacemaker function of the sinus node. The drug has been approved for the treatment of angina and heart failure. There is some evidence of its role as an inhibitor of atrial-ventricular node (AVN) conduction. The aim of the BRAKE-AF project is to assess ivabradine use for rate control in atrial fibrillation (AF).
A multicenter, randomized, parallel, open-label, noninferiority phase III clinical trial will be conducted to compare ivabradine vs digoxin in 232 patients with uncontrolled permanent AF despite beta-blockers or calcium channel blockers. The primary efficacy endpoint is the reduction in daytime heart rate measured by 24-hour Holter monitoring at 3 months. This clinical trial will be supported by an electrophysiological study of the effect of ivabradine on the action potential of the human AVN. To do this, an experimental model will be used with Chinese hamster ovarium cells transfected with the DNA encoding the expression of the t channels involved in this action potential and recording of the ionic currents with patch clamp techniques.
New data will be obtained on the effect of ivabradine on the human AVN and its safety and efficacy in patients with permanent AF.
The results of the BRAKE-AF project might allow inclusion of ivabradine within the limited arsenal of drugs currently available for rate control in AF.
Clinical trial registration: http://www.clinicaltrials.gov. Identifier: NCT03718273.
La ivabradina es un inhibidor de la corriente If, principal determinante de la función marcapasos del nódulo sinusal, aprobado como antianginoso y para tratar la insuficiencia cardiaca. Existen indicios sobre su capacidad para inhibir la conducción a través del nódulo auriculoventricular (NAV). Sobre esta base, el proyecto BRAKE-AF plantea el uso de ivabradina como agente cronotrópico negativo en fibrilación auricular (FA).
Se realizará un ensayo clínico multicéntrico de fase III, aleatorizado, abierto, en paralelo, con diseño de no inferioridad, para comparar la ivabradina frente a la digoxina en 232 pacientes con FA permanente no controlada con bloqueadores beta o antagonistas del calcio; el objetivo primario es la reducción de la frecuencia cardiaca media diurna en un Holter de 24h a los 3 meses. El ensayo se apoyará en un estudio electrofisiológico que analizará el efecto de la ivabradina en el potencial de acción del NAV humano, utilizando un modelo experimental en células de ovario de hámster chino transfectadas con el ADN que codifica la expresión de los distintos canales que componen dicho potencial de acción, registrando las corrientes iónicas mediante la técnica del parche de membrana.
Se obtendrá información tanto del efecto de la ivabradina en las corrientes iónicas y el potencial de acción del NAV como de su eficacia y su seguridad en pacientes con FA permanente.
Los resultados del proyecto BRAKE-AF podrían permitir que la ivabradina se incluyera en el limitado arsenal de fármacos disponibles actualmente para el control de frecuencia en la FA.
Ensayo registrado en ClinicalTrials.gov (Identificador: NCT03718273)</abstract><cop>Spain</cop><pub>Elsevier España, S.L.U</pub><pmid>31631048</pmid><doi>10.1016/j.rec.2019.09.004</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1885-5857 |
| ispartof | Revista española de cardiología (English ed.), 2020-05, Vol.73 (5), p.368-375 |
| issn | 1885-5857 1885-5857 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2307394861 |
| source | MEDLINE; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Action potential Anti-Arrhythmia Agents - therapeutic use Atrial Fibrillation - drug therapy Atrioventricular node Cardiovascular Agents - therapeutic use Control de frecuencia Digoxin Digoxin - therapeutic use Digoxina Equivalence Trials as Topic Fibrilación auricular permanente Heart Rate - drug effects Heart Rate - physiology Humans Ivabradina Ivabradine Ivabradine - therapeutic use Nódulo auriculoventricular Parche de membrana Patch clamp Persistent atrial fibrillation Potencial de acción Rate control Treatment Outcome |
| title | Ivabradine for chronic heart rate control in persistent atrial fibrillation. Design of the BRAKE-AF project |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T22%3A09%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ivabradine%20for%20chronic%20heart%20rate%20control%20in%20persistent%20atrial%20fibrillation.%20Design%20of%20the%20BRAKE-AF%20project&rft.jtitle=Revista%20espa%C3%B1ola%20de%20cardiolog%C3%ADa%20(English%20ed.)&rft.au=Fontenla,%20Adolfo&rft.aucorp=on%20behalf%20of%20the%20BRAKE-AF%20investigators&rft.date=2020-05&rft.volume=73&rft.issue=5&rft.spage=368&rft.epage=375&rft.pages=368-375&rft.issn=1885-5857&rft.eissn=1885-5857&rft_id=info:doi/10.1016/j.rec.2019.09.004&rft_dat=%3Cproquest_cross%3E2307394861%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2307394861&rft_id=info:pmid/31631048&rft_els_id=S1885585719302877&rfr_iscdi=true |