Actualización en el tratamiento de la Estenosis Aórtica Severa.
¿Debería cambiarse la indicación tras el estudio Partner?
Dra Pilar Tornos Hospital Vall d’Hebron Congreso Nacional de Cardiologia, 2011
Management of Severe Aortic Stenosis
Severe AS (< 1 cm² or < 0.6 cm²/m² BSA) Symptoms No
Yes
LV EF < 50%
No Yes
Markedly calcified valve and increase in peak jet velocity ≥ 0.3 m/sec within 1 year
No
Yes Patient physically active
Yes
Exercise test No Re-evaluate in 6 to 12 months or when symptoms occur
Normal
Abnormal Surgery
Guidelines ESC,2007
Ademas del estudio Partner, ¿Qué hemos aprendido en los últimos 5 años sobre el manejo de la EA? • Importancia de la correcta definición de estado sintomático • Importancia de poder predecir la evolución – Papel de la prueba de esfuerzo – Papel del Eco de esfuerzo – Grado de calcificación – Papel del BNP – Papel de la severidad de la EA
Kaplan-Meier plot of cumulative symptom-free survival over 12 months according to the incidence of limiting symptoms on baseline exercise testing
Das, P. et al. Eur Heart J 2005 26:1309-1313
Ecocardiograma de ejercicio? • •
69 pts asintomáticos con EA severa (area<1cm2) Incremento del gradiente (>18 mm Hg) era un factor predictivo independiente de aparición de síntomas en un seguimiento de 15 meses.
Lancelloti et al, Circulation 2005
Rosenhek, Circulation 2010
CORRECTO MANEJO DE LA EA SEVERA
OPTIMIZAR LA VALORACIÓN DEL PACIENTE “ASINTOMÁTICO”
Correcta evaluación de síntomas incipientes BNP Prueba de esfuerzo Progresión rápida EA críticas
CIRUGIA
Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery? Bernard Iung, Agnès Cachier, Gabriel Baron, David Messika-Zeitoun, François Delahaye, Pilar Tornos, Christa Gohlke-Bärwolf, Eric Boersma, Philippe Ravaud and Alec Vahanian
REASONS THAT AORTIC VALVE REPLACEMENT WAS NOT PERFORMED AS during 2005 155 patients with severe AS In 75 surery was not performed 22 asymptomatic 53 symptomatic
Calculated operative risk was 11-13% Only 35% evaluated by a surgeon
Symptomatic pts (n = 53)
Prohibitive comorbidities
30 (57%)
Symptoms felt due to another etiology
11 (21%)
Died before surgery Presented in cardiogenic shock
2 (4%)
Planned elective surgery
2 (4%)
Subvalvular obstruction
3 (6%)
Aortic stenosis unrecognized
3 (6%)
Patient declined intervention
2 (4%)
Bach, D. S. et al. J Am Coll Cardiol 2007;50:2018-2019
Supervivencia de pacientes con EA no operada
Bach, D. S. et al. J Am Coll Cardiol 2007;50:2018-2019
Cirugía de recambio valvular por estenosis aórtica severa en mayores de 80 años. Experiencia de un centro en una serie de pacientes consecutivos David Calvo et al Rev Esp Cardiol 2007; 60: 720 - 726 137 pacientes con EA severa edades entre 80 y 87 años, media 81 MORTALIDAD QUIRURGICA: 3.8%
33 se rechazó cirugía (24%)
Nueva modalidad terapĂŠutica: TAVI
Nueva modalidad terapĂŠutica: TAVI 2004
Mas de 60.000 pts partner
2011
PARTNER Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened
Total = 1,057 patients
N = 699
High Risk
Inoperable
2 Parallel Trials: Individually Powered
N = 358
ASSESSMENT:
Transfemoral Access Yes
No
1:1 Randomization
N = 179
N = 179
TF TAVR
Standard Therapy
Not In Study
VS Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority)
Inoperable PARTNER Cohort Primary Endpoint: All-Cause Mortality Standard Rx
All-cause mortality (%)
TAVI
â&#x2C6;&#x2020; at 1 yr = 20.0% NNT = 5.0 pts
HR [95% CI] = 0.54 [0.38, 0.78] P (log rank) < 0.0001
50.7%
30.7%
Months
Leon et al, NEJM 2010; 363:1597-1607 Numbers at Risk TAVI Standard Rx
179 179
138 121
122 83
67 41
26 12
PARTNER Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened
Total = 1,057 patients
N = 699
High Risk
Inoperable
2 Parallel Trials: Individually Powered
ASSESSMENT: Yes
Transfemoral Access
Transfemoral (TF)
1:1 Randomization
ASSESSMENT: No
Transfemoral Access
Transapical (TA)
1:1 Randomization
Yes
No
1:1 Randomization
N = 244
N = 248
N = 104
N = 103
N = 179
N = 179
TF TAVR
AVR
TA TAVR
AVR
TF TAVR
Standard Therapy
VS
N = 358
VS
Primary Endpoint: All-Cause Mortality at 1 yr (Non-inferiority)
Not In Study
VS Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority)
Study Devices
Edwards SAPIEN THV 23 and 26 mm valves
RetroFlex
Ascendra
22 and 24 F sheaths 24 and 26 F sheaths
Transfemoral and Transapical
Transfemoral
Transapical
Inclusion Criteria • Severe AS: Echo-derived AVA < 0.8 cm2 (or AVA index < 0.5 cm2/m2) and mean AVG > 40 mm Hg or peak jet velocity > 4.0 m/s
• Cardiac Symptoms: NYHA Functional Class ≥ II • High surgical risk: Predicted risk of operative mortality ≥ 15% (determined by site surgeon and cardiologist); guideline = STS score ≥ 10
Randomized = 699 patients TF = 492 TA = 207
Transfemoral n = 492
Transapical n = 207
TAVR (244)
AVR (248)
TAVR (104)
AVR (103)
30 Days (236)
30 Days (223)
30 Days (100)
30 Days (92)
Dead = 8 Withdrawal = 0
1 Year (189) Dead = 46 Withdrawal = 1
Dead = 15 Withdrawal = 10
1 Year (168) Dead = 47 Withdrawal = 8
Dead = 4 Withdrawal = 0
1 Year (73) Dead = 26 Withdrawal = 0 LTFU = 1
42 Patients not treated as assigned
Dead = 7 Withdrawal = 4
1 Year (68) Dead = 20 Withdrawal = 3 LTFU = 1
Primary Endpoint: All-Cause Mortality at 1 Year 0.5
HR [95% CI] = 0.93 [0.71, 1.22] P (log rank) = 0.62
TAVR AVR
0.4
26.8
0.3 0.2
24.2
0.1 0 0
6
No. at Risk
12
18
24
Months
TAVR
348
298
260
147
67
AVR
351
252
236
139
65
Primary Endpoint: All-Cause Mortality at 1 Year
TAVR
AVR
(N = 348)
(N = 351)
24.2%
Difference Upper 1-sided 95% CI
26.8%
-2.6%
Noninferiority P value
3.0%
= 0.001
Zone of non-inferiority pre-specified margin = 7.5%
Non-inferior
-3.0
-2.0
-1.0
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0 %
Upper one-sided 95% CI
Primary Non-Inferiority Endpoint Met
All-Cause Mortality Transfemoral (N=492) HR [95% CI] = 0.83 [0.60, 1.15] P (log rank) = 0.25 26.4
22.2
No. at Risk
Months
TAVR
244
215
188
119
59
AVR
248
180
168
109
56
Powered Secondary Endpoint (ITT): TF All-Cause Mortality at 1 Year
TAVR
AVR
(N = 248)
(N = 244)
22.2%
Difference
-4.2%
Noninferiority P value
2.3%
= 0.002
Upper 1-sided 95% CI
26.4%
Zone of non-inferiority pre-specified margin = 7.5% Non-inferior
-5.0
-4.0
-3.0
-2.0
-1.0
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
Upper one-sided 95% CI
Secondary TF Non-Inferiority Endpoint Met
8.0 %
All-Cause Mortality Transapical (N=207) HR [95% CI] = 1.22 [0.75, 1.98] P (log rank) = 0.41
29.0
27.9
No. at Risk
Months
TAVR
104
83
72
28
8
AVR
103
72
68
30
9
Surgical AVR Outcomes • Using an established predictive risk model (STS), the expected (“E”) 30-day mortality after AVR was 11.8%. • The observed (“O”) 30-day mortality in the as-treated AVR control group was 8.0%. • O:E = 0.68 indicates better than predicted surgical outcomes in the control AVR patients. • There were no significant site or surgeon differences.
Conclusions (1) • The primary endpoint of the trial was met: – In patients with aortic stenosis at high risk for operation, TAVR was non-inferior to AVR for all-cause mortality at 1 year (24.2% vs. 26.8%, p=0.001 for non inferiority) – Transfemoral TAVR subgroup was also non-inferior to AVR (p=0.002 for non-inferiority)
• Death at 30 days was lower than expected in both arms of the trial: – TAVR mortality (3.4%) was the lowest reported in any series, despite an early generation device and limited previous operator experience – AVR mortality (6.5%) was lower than the expected operative mortality (11.8%)
Conclusions (2) • Both TAVR and AVR were associated with important but different peri-procedural hazards: – Major strokes at 30 days (3.8 vs. 2.1%, p=0.20) and one year (5.1% vs. 2.4%, p=0.07) and major vascular complications were more frequent with TAVR (11.0% vs. 3.2%, p<0.001) – Major bleeding (9.3% vs. 19.5%, p<0.001) and new onset atrial fibrillation (8.6% vs. 16.0%, p<0.001) were more frequent with AVR
• TAVR and AVR are both acceptable therapies in these high-risk patients; differing peri-procedural hazards should influence case-based decision-making
Implications â&#x20AC;˘ A multidisciplinary valve team approach benefits patients and is recommended for all future valve centers. â&#x20AC;˘ TAVR is already the standard-of-care for inoperable patients with severe aortic stenosis. These results indicate that TAVR is an acceptable alternative to AVR in selected high-risk operable patients.
â&#x20AC;˘ Future randomized studies should focus on lower risk patients who are candidates for operation.
Experiencia HGUVH en pacientes con EA severa de alto riesgo (6/2008-9/2011) - Enfermos evaluados: 200
- Implantados: 78 - Mortalidat intrahospitalaria: 3/78 (3,8%) - Mortalidat 1 a帽o: 10/76 (9,2%) - En lista de espera actual: 18 - Contraindicados: 29 (mortalidad 14/29:48%).
- Mortalidat en periodo de screening y/o lista de espera: 21 - Numero de valvuloplastias con intenci贸n puente y/o paliaci贸n: 50
Análisis económico de la implantación percutánea de prótesis valvulares aórticas en pacientes con estenosis valvular severa: resultados preliminares. Ignácio Ferreira-González, V. Serra, O. Abdul, L. Lizan, S.Paz, K. Banz, C. Sureda, A.Igual, B. García Del Blanco, J .Angel, D. García-Dorado, P. Tornos. 1Unidad
de Epidemiología, Unidad de Hemodinámica y Servicio de Cirugía Cardiaca, Hospital Vall d'Hebron, Barcelona y CIBER de Epidemiología y Salud Pública (CIBERESP). 2Outcomes’10, Castellón. 3 Outcomes International, Basel, Suiza.
RESULTADOS (III) Plano de coste-efectividad incremental. Análisis de sensibilidad probabilístico.
Tanto TA TAVI como TF TAVI proporcionan mejores resultados clínicos a un coste económico mayor que el tratamiento médico conservador ubicándose en el cuadrante superior derecho del plano de coste-efectividad incremental. ►Esta posición obliga al decisor en salud a valorar el coste de oportunidad que puede derivar de decidir la utilización de TAVI en el ámbito sanitario público español. 34 ►
Tratamiento de la EA severa 2011 • Intentar disminuir el riesgo quirúrgico del recambio valvular convencional:. Adelantar el momento quirúrgico para disminuir el riesgo y ofercer un tratamiento con muy buenos resultados contrastados a largo plazo. • En los pacientes sintomáticos y con riesgo quirúrgico prohibitivo proceder a TAVI. Evidencia científica y estudios de coste eficacia que avalan esta actitud. • En pacientes de alto riesgo los resultados del estudio Partner sugieren que el TAVI es una buena alternativa. • Por el momento extender las indicaciones de TAVI a todos los pacientes sintomáticos parece prematura, fundamentalmente porque hacen falta mas estudios de seguimiento y durabilidad de las prótesis implantadas, y tambien porque las cifras de morbimortalidad del recambio valvular convencional son cada vez mejores
Comentarios finales â&#x20AC;˘ El estudio Partner y la experiencia TAVI recogida en los diferentes registros establece claramente que el TAVI es un procedimiento que debe considerarse ante todo paciente con EA severa sintomatica que no puede ser operado. â&#x20AC;˘ Posiblemente tambien es el procedimiento de eleccion en pacientes considerados de alto riesgo para cirugia. El principal problema es la definicion de alto riesgo quirurgico. â&#x20AC;˘ Es por ello que las indicaciones de TAVI vs Cirugia convencional vs Tratamiento medico deben ser consensuadas en equipos que incluyan cardiologo clinico, intervencionista y cirujano