CHICAGO

March 29

Dapagliflozin after Transcatheter Aortic Valve Implantation

Sergio Raposeiras-Roubin, MD, PhD

EudraCT 2020-003930-18
ClinicalTrials.gov Identifier: NCT04696185
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@DapaTAVI @S_Raposeiras
 Disclosures

DapaTAVI is an independent trial

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All authors declare no conflicts of interest related to this study

FUNDING: DapaTAVI received partial financial from unrestricted grants from the Spanish Government
[Instituto de Salud Carlos III (ISCIII; FIS PI19/01882)], the Castilla-León Government [Gerencia Regional de
Salud de la Junta de Castilla y León y Fondos FEDER (2459/A/21; GRS 2459/A/21, 2022)], the Spanish
Society of Cardiology (SEC/FEC-INV-CLI 21/004) and the Galician Society of Cardiology (SOGACAR 2022).

Promotors: Spanish Society of Cardiology and Spanish National Center for Cardiovascular Research

Sergio Raposeiras-Roubín, MD, PhD

Background

AORTIC STENOSIS is one of

the most common VHD
Despite TAVI, PATIENTS STILL FACE HIGH
RATES OF HEART FAILURE
TAVI has changed how aortic
stenosis is managed

Patients with HF secondary to VHD or

SGLT2i have shown benefit
undergoing valvular interventions were
in all spectrum of HF
excluded from RCT with SGLT2i

Patients undergoing TAVI Patients > 80 years are

tend to be elderly underrepresented in RCT with SGLT2i

Sergio Raposeiras-Roubín, MD, PhD

Background

We need evidence on EFFICACY of

SGLT2i in TAVI patients

We need evidence on SAFETY of

SGLT2i in very elderly patients

Sergio Raposeiras-Roubín, MD, PhD

Trial design

Prospective Randomized Open

Blinded Endpoint (PROBE) Independent and pragmatic
controlled trial
The protocol was approved by the Galician Clinical Research Ethics Committee (approval number 2020/434), the
Spanish Agency of Medicines and Medical Devices (AEMPS 20-0748), and the investigational review boards at each of
the participating sites.
The trial was registered in both ClinicalTrials.gov (NCT04696185) and the European Clinical Trials Database (EUDRACT
2020-003930-18).

Randomization 1:1 Dapagliflozin

Stratified by the presence of diabetes mellitus, a
LVEF≤40%, and an eGFR 25-75 ml/min/1.73 m2
At time of hospital discharge after
TAVI or within 14 days of discharge. No
Dapagliflozin

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Sergio Raposeiras-Roubín, MD, PhD
Inclusion/Exclusion Criteria

Sergio Raposeiras-Roubín, MD, PhD

 Endpoints

PRIMARY • Composite of all-cause death or worsening HF

ENDPOINT (defined as any hospitalization for HF or urgent HF visit requiring iv diuretics)
3 months

• All-cause death
1 year SECONDARY • Hospitalization for HF and urgent HF visit requiring iv diuretics
• Cardiovascular death
ENDPOINTS
• Composite of hospitalization for HF or cardiovascular death
Telephone interviews
Review of medical records
National vital status registries

Clinical outcomes were externally adjudicated by a clinical panel blinded to

treatment
Sergio Raposeiras-Roubín, MD, PhD
Study population

Multicenter: 39 centers across Spain

Recruitment by center 1,257

Number of patients
39 HOSPITALS
January December
2021 2023

SPAIN

14 regions

Sergio Raposeiras-Roubín, MD, PhD

Recruitment
Recruitment rate 1,020 23% 1,257

CALCULATION OF SAMPLE SIZE

Anticipated event of primary composite outcome:
30% in control group
Dapagliflozin associated with 30% RRR (80% power)
Estimated loss during follow-up of 5%

Sergio Raposeiras-Roubín, MD, PhD

Patient flow

© Copyright 2025
Sergio Raposeiras-Roubín, MD, PhD
Randomization and cross-overs

Total crossover rate = 12%

Dapagliflozin Crossovers 103

N=605 (17%)

Stopping treatment with dapagliflozin during the follow-up

2 days (1-4)
No
Dapagliflozin Crossovers 43
N=617 (7%)

RANDOMIZATION Initiation of STGL-2 inhibitors for reasons other than HF

Sergio Raposeiras-Roubín, MD, PhD

Baseline Characteristics
Dapagliflozin Group Control Group
Characteristic
(N = 605) (N = 618*)
Age — yr 82.4±5.6 82.4±5.5
Female sex — no. (%) 299 (49.4) 305 (49.4)
Diabetes mellitus type 2 — no. (%) 264 (43.6) 273 (44.2)
Hypertension — no. (%) 518 (85.6) 519 (84.0)
Coronary artery disease — no. (%) 237 (39.2) 197 (31.9)
Previous myocardial infarction — no. (%) 51 (8.4) 52 (8.4)
Prior stroke — no. (%) 61 (10.1) 69 (11.2)
Peripheral artery disease — no. (%) 51 (8.4) 43 (7.0)
Atrial fibrillation — no. (%) 250 (41.3) 274 (44.3)
Estimated GFR — ml/min/1.73 m2 56.0±16.4 56.4±16.3
Left ventricular ejection fraction — % 54.9±12.3 54.8±12.1
New-onset bundle branch block — no. (%) 151 (32.0) 146 (32.6)
Pacemaker implantation — no. (%) 105 (19.3) 103 (19.0)
Post-TAVI aortic regurgitation grade 3+ — no. (%) 27 (4.5) 37 (6.0)
* 1 patient was lost to follow-up
Sergio Raposeiras-Roubín, MD, PhD
 Baseline Characteristics
49.4% women
43,9%
82,4 ± 5,5 years (n=537)
Median 83 years (IQR 79-86)
Diabetes
Frequency

17%
(n=212)

LVEF ≤ 40%

From 60 to 99 years
88,6%
(n=1,084)
Age (years)
7,4% ≥ 90 y
CKD-EPI 25-75
Sergio Raposeiras-Roubín, MD, PhD
RESULTS: Primary
30
end-point (intention to treat analysis)
25
Control Group: 124 patients (20.1%)
20 Dapagliflozin Group: 91 patients (15.0%)

15

10

5 HR 0.72 (95% CI 0.55-0.95)

P=0.018
0
0 30 60 90 120 150 180 210 240 270 300 330 360
Days since Randomization
No. at Risk
Control 617 588 572 558 551 543 537 528 524 517 511 507 493
Dapagliflozin 605 592 581 570 564 560 550 543 536 532 522 520 514
© Copyright 2025
Sergio Raposeiras-Roubín, MD, PhD
RESULTS: Primary end-point (per protocol analysis)

HR 0.67 (95% CI 0.49-0.90)

© Copyright 2025
Sergio Raposeiras-Roubín, MD, PhD
 RESULTS: Subgroup analysis

The effect of dapagliflozin

on the primary outcome
also appeared consistent
across prespecified
subgroups

© Copyright 2025
Sergio Raposeiras-Roubín, MD, PhD
RESULTS: Secondary end-points

All-cause Death Worsening HF

Control Group: 56 patients (9.1%) Control Group: 89 patients (14.4%)
Dapagliflozin Group: 47 patients (7.8%) Dapagliflozin Group: 57 patients (9.4%)

HR 0.87 (95% CI 0.59-1.28) HR 0.63 (95% CI 0.45-0.88)

© Copyright 2025
Sergio Raposeiras-Roubín, MD, PhD
RESULTS: Secondary end-points
Hospitalization for HF Urgent HF Visit
HR 0.68 (95% CI 0.46-0.99) HR 0.46 (95% CI 0.26-0.82)

Cardiovascular Death CV Death or Hospitalization for HF

HR 0.81 (95% CI 0.49-1.35) HR 0.71 (95% CI 0.51-0.98)

© Copyright 2025
Sergio Raposeiras-Roubín, MD, PhD
RESULTS: Safety end-points
Dapagliflozin Group Standard care Group
(N = 605) (N = 617)
End Point Incidence Incidence P-value
Value no. of events per Value no. of events per
100 patient-yr 100 patient-yr
Genitourinary infections 94 15.5 71 11.5 0.04
Genital infections 11 1.8 3 0.5 0.03
Urinary infections 83 13.7 68 11.0 0.15
Relevant urinary infections 17 2.8 11 1.8 0.23
Bacteremia 31 5.1 32 5.2 0.96
Hypotension 40 6.6 22 3.6 0.01
Syncope 22 3.6 13 2.1 0.11
Ketoacidosis 0 0 0 0 -
Major Hypoglycemia 4 0.7 8 1.3 0.26
Necrotizing fasciitis 0 - 0 - -
Non-traumatic amputation 5 0.8 4 0.6 0.72
Cancer 30 5 22 3.6 0.23

Sergio Raposeiras-Roubín, MD, PhD

CONCLUSION

Among patients with aortic stenosis undergoing TAVI and at high

risk for heart failure, dapagliflozin reduced the incidence of all-
cause death or worsening heart failure compared to standard care

Sergio Raposeiras-Roubín, MD, PhD

 Acknowledgments
LIST OF INVESTIGATORS: Hospital Clínico Santiago: Diego López Otero, Xoan Carlos Sanmartín Pena, Javier López País, José Ramón Gonzalez
Juanatey. Hospital Clínico San Carlos: Luis Nombela Franco, Gabriela Tirado, Carlos Real, Nieves Gonzalo López, Pablo Salinas Sanguino, Pilar
Thanks to all patients and DapaTAVI family Jiménez Quevedo, Antonio Fernández Ortiz. Hospital Puerta del Mar: Livia Gheorge, German Calle, Alejandro Gutierrez Barri. Hospital La Fe
Valencia: Francisco Ten Morro, Elena Sánchez Lacuesta, Bernabé López Ledesma, Jorge Sanz-Sánchez. Hospital Universitario de Valladolid:
Ignacio Amat Santos, Carlos Baladrón Zorita, José Raúl Delgado Arana, Alejandro Barrero, Sandra Santos, Esther Sanz Patiño, Javier Gómez-
†DapaTAVI Colaborators: Pablo Domínguez-Erquicia, María Melendo-Viu, María Cespón- Herrero, Clara Fernandez-Cordón, Mario García Gómez, Marcelo Rodriguez, Akash Jain. Hospital Álvaro Cunqueiro: Sergio Raposeiras Roubín,
Fernández, Rodrigo Estévez-Loureiro, Javier López-Pais, José Ramón González-Juanatey, Pablo Domínguez-Erquicia, Rodrigo Estévez-Loureiro, Lucía Riobóo Lestón, Ana Ledo, Antonio De Miguel, Saleta Fernández, Víctor Jiménez Díaz,
Gabriela Tirado, Alejandro Gutierrez-Barri, Jorge Sanz-Sánchez, Javier Gómez-Herrero, Erika Berenice Caneiro Queija, Alberto Ortiz, Guillermo Bastos, Rocío González Ferreiro, Inmaculada González Bermúdez, Juan Ocampo Míguez,
Muñoz García, Xavier Carrillo Suares, Manuel Pan-Álvarez, Gabriela Veiga-Fernández, Jesús Rafael Cobas Paz, Andrea Lizancos, Francisco Calvo. Hospital Virgen de la Victoria: Antonio Jesús Muñoz García, Erika Muños García, Juan H
Jiménez Mazuecos, Juan Miguel Ruiz Nodar, Xacobe Flores Rios, Ignacio Ferreira, Jorge Alonso Briales, Javier Alcaide. Hospital German Trias i Pujol: Victoria Vilalta del Olmo, Eduard Fernandez Nofrerias, Xavier Carrillo Suares, Edgar
Palazuelos Molinero, Pablo Avanzas, Juan Sanchís, Antonio Piñeiro Lozano, Javier Moreiras, Fadeuilhe Grau. Hospital Reina Sofía: Manuel Pan Álvarez, Soledad Ojeda, Javier Suarez de Lezo, Jorge Perea, Francisco J. Hidalgo. Hospital
Lluis Asmarats Serra, Manuel Villa Gil-Ortega, Fernando Sarnago Cebada, José Francisco Díaz Marqués de Valdecilla: José María De la Torre, Gabriela Veiga Fernández. Hospital Universitario de Albacete: Juan Gabriel Córdoba Soriano,
Fernández, Geoffrey Yanes Bowden, Roberto Blanco Mata, María Molina Jiménez, Manuel
Jesús Jiménez Mazuecos, Arsenio Gallardo López. Hospital Clinic Barcelona: Ander Regueiro, Endaitz Estebanez, Pedro Cepas. Hospital General
López Pérez, Raul Ramallal Martínez, Luis Manuel Domínguez Rodríguez, Antonio Morcuende
de Alicante: Pascual Bordes Siscar, Juan Miguel Ruiz Nodar, Miriam Sandín Rollán, Juan Quiles, Raquel Ajo Ferrer, María Ajo Ferrer, Marta
González, Juan Ruiz-García, Rosa Fernández Olmo, Marta Cobo, María López Benito, José
Herrero, Vicente Mainar, José Valencia Martín, Javier Pineda Rocamora, Fernando J. Torres Mezcua, Teresa Lozano Palencia. Hospital Juan
Antonio Diarte de Miguel, Juan Carlos SanMartín Pena, Diana Pereiro Montes, Carlos Real,
Nieves Gonzalo López, Pablo Salinas Sanguino, Pilar Jiménez Quevedo, Antonio Fernández Canalejo de Coruña: Jorge Salgado Fernández, Xacobe Flores Ríos, Elizabet Méndez Eirín, María Soto Núñez.Hospital Vall de Hebrón: Bruno
Ortiz, German Calle, Bernabé López Ledesma, Francisco Ten Morro, Elena Sánchez Lacuesta, García, Ignacio Ferreira, Aitor Uribarri, Ricardo Palma. Hospital La Luz de Madrid: Roberto Martín Reyes, Jorge Palazuelos Molinero, Daniele
Clara Fernandez-Cordón, Mario García Gómez, Marcelo Rodriguez, Akash Jain, Lucía Riobóo Gemma, Ana Lucía Rivero Monteagudo. Hospital Bellvitge: Rafael Romaguera, Josep Comin Colet, Joan A. Gomez-Hospital. Hospital
Lestón, Ana Ledo, Antonio De Miguel, Saleta Fernández, Víctor Jiménez Díaz, Berenice Universitario de Asturias: Cesar Morís, Pablo Avanzas, Ana Ayesta. Hospital Clínico Valencia: Sergio García Blas, Juan Sanchis Forés, Julio Núñez
Caneiro Queija, Alberto Ortiz, Guillermo Bastos, Juan Ocampo Míguez, Andrea Lizancos, Villota, Gema Miñana Escriva, Ernesto Valero Picher, Jesskika González D´Gregorio, Agustín Fernández Cisnal, Clara Bonanad Lozano. Hospital
Francisco Calvo, Juan H Alonso Briales, Javier Alcaide, Edgar Fadeuilhe Grau, Eduard Fernandez Universitario Fundación Jiménez Díaz: Borja Ibáñez, Sandra Gómez-Talavera, Juan A Franco-Peláez, Felipe Navarro del Amo, Antonio Piñeiro,
Nofrerias, Javier Suarez de Lezo, Jorge Perea, Francisco J. Hidalgo, Arsenio Gallardo López, Paloma Avila, José A. Esteban-Chapel, María López Álvarez, Alba Vega-Viyuela, José Tuñón.Hospital Universitario de Salamanca: Ignacio Cruz,
Vicente Mainar, José Valencia Martín, Javier Pineda Rocamora, Fernando J. Torres Mezcua, Javier Moreiras, Pablo Antúnez-Muíños, Sergio López-Tejero.Hospital Sant Pau: Dabit Arzamendi, Lluis Asmarats. Hospital Virgen del Rocío:
Juan Manuel Quiles Granado, Teresa Lozano Palencia, Miriam Sandín Rollán, Juan Quiles, Manuel Villa Gil-Ortega, Nieves Romero Rodríguez, Alba Abril Molina, Elena Jiménez Xarrié, Antonio Delgado Ariza, Carlos Millán Rodríguez,
Raquel Ajo Ferrer, María Ajo Ferrer, Marta Herrero, Elizabet Méndez Eirín, María Soto Núñez, Belén de la Fuente Perdomo. Hospital 12 de Octubre: Fernando Sarnago Cebada, Agustín Albarrán, Felipe Díez-del Hoyo. Hospital Juan Ramón
Aitor Uribarri, Ricardo Palma, Daniele Gemma, Ana Lucía Rivero Monteagudo, Ana Ayesta, Jiménez: José Francisco Díaz Fernández, Santiago Camacho Freire. Hospital Universitario de Canarias: Francisco Bosa Ojeda, Geoffrey Yanes
Clara Bonanad Lozano, Paqui Esteve Claramunt, Regina Blanco del Burgo, Daznia Bompart, Bowden, Belén de la Fuente Perdomo. Hospital Cruces: Roberto Mata, Juan Carlos Astorga Burgo. Hospital Virgen de las Nieves: Eduardo
Gema Miñana Escriva, Ernesto Valero Picher; Jesskika González D´Gregorio, Agustín Fernández
Molina Navarro, Rocio Parrilla Linares, María Molina Jiménez, Teresa Bretones. Hospital San Cecilio de Granada: Juan Caballero Borrego,
Cisnal, Luis Nieto Roca, Sandra Gómez Talavera, Felipe Navarro del Amo, Antonio Piñero,
Manuel López Pérez. Hospital Navarra: Valeriano Ruiz Quevedo, Raul Ramallal Martínez, Guillermo Sanchez Elvira, Pablo Bazal Chacon, Raul
Paloma Ávila, José A. Esteban-Chapel, José Tuñón, María López Álvarez, Alba Vega-Viyuela,
Millán Segovia. Hospital Ramón y Cajal: Ángel Sánchez Recalde, María Abellás, Luis Manuel Domínguez Rodríguez. Hospital Son Espases:
Pablo Antúnez-Muíños, Sergio López-Tejero, Rocio Parrilla Linares, Alba Abril Molina, Elena
Jiménez Xarrié, Antonio Delgado Ariza, Carlos Millán Rodríguez, Belén de la Fuente Perdomo, Vicente Peral Disdier, Antonio Morcuende González, Raul Millán Segovia, Marcos Pascual Sastre, Jaume Maristany Daudert. Hospital
Maria Abellas, Guillermo Sanchez Elvira, Pablo Bazal Chacon, Raul Millán Segovia, Marcos Universitario de Torrejón: Eduardo Alegría-Barrero. Hospital de Jaén: Javier Torres-Llergo, Rosa Fernández Olmo, Miguel Puentes Chiachío,
Pascual Sastre, Jaume Maristany Daudert, Angeles Gelines Garcia Fernandez, Miguel Puentes Jesús Marchal Martínez. Hospital Nuestra Señora de América: Gisela Feltés. Hospital Puerta de Hierro: Jose Antonio Fernández Díaz, Marta
Chiachío, Jesús Marchal Martínez, Felipe Fernández Vázquez, Armando Pérez de Prado, María Cobo. Hospital León: Carlos Cuellas, María López Benito, Felipe Fernández Vázquez, Armando Pérez de Prado, María Cruz Ferrer, María Thiscal,
Cruz Ferrer Gracia, Ana García-Álvarez, Pablo García-Pavía, Noemí Escalera. Angeles Gelines Garcia Fernandez. Clínica Teknon: Gustavo David Jimenez Britez. Hospital Miguel Servet Zaragoza: Juan Sánchez-Rubio
Lezcano, José Antonio Diarte de Miguel, María Cruz Ferrer Gracia

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Sergio Raposeiras-Roubín, MD, PhD
Publication

Sergio Raposeiras-Roubín, MD, PhD