cambiar-indicación-tras-estudio-partner

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