AATS Annual Meeting 2015 | Seattle, WA | April 27, 2015

Appropriate Patient Selection or Healthcare Rationing? Lessons from Surgical Aortic Valve Replacement in The PARTNER I Trial

Wilson Y. Szeto, MDon behalf of The PARTNER Trial Investigatorsand The PARTNER Publications Office

• Investigator, Steering committee member of the PARTNER trial

• Edwards Lifesciences

Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

Disclosure Statement of Financial Interest

Wilson Y. Szeto, MD

Background

• Surgical aortic valve replacement (SAVR) is being challenged by transcatheter aortic valve replacement (TAVR) for patients considered at high surgical risk.

• There is increasing pressure on surgeons and institutions to improve quality metrics and outcomes while reducing cost of medical care.

• Surgeons considering SAVR in high risk patients risk failing quality metrics.

Objectives / Questions

The Placement of Aortic Transcatheter Valves (PARTNER) trial provides insight into outcomes after surgical AVR in high-risk patients at extreme of traditional indications for SAVR.

1) Are surgical outcomes after high risk SAVR accurately predicted by current national benchmarks?

2) Is intermediate term survival after high risk AVR commensurate with that of the matched general population seen in previous studies?

3) Is there a subset of elderly patients whose risk of mortality after SAVR is exceptionally high (with survival worse than treatment without AVR, i.e. futility)?

Study Design

Symptomatic Severe Aortic Stenosis

ASSESSMENT: High-Risk AVR Candidate3,105 Total Patients Screened

Cohort B (Inoperable) n=358

Cohort A (High Surgical Risk)n=699

Did not undergo SAVR (n=38)

- Died before procedure: 5- Deteriorated before

procedure: 5- Refused: 17- Withdrew: 11

Crossover from TAVR to Medical Therapy: 2

Allocated to SAVRn=351

Allocated to Medical Therapyn=179

Received Medical Therapyn=181

ReceivedSAVRn=351

Allocated to TAVR

(n=348)

Allocated to TAVR

(n=179)

Patient Population

• 699 patients with severe symptomatic AS were enrolled into PARTNER 1A from 2007-2009.

• Of the 351 patients randomized to SAVR, 313 underwent AVR (as treated cohort).

– 28 patients withdrew / refused therapy– 10 patients deteriorated to an inoperable status

• 181 patients in PARTNER 1B (inoperable cohort) randomized to medical therapy were used as reference for survival without valve replacement.

Methodology

• Procedural outcome and primary safety endpoints were compared to national quality benchmarks for SAVR defined according to the STS Database Version 2.61.

• Intermediate term survival comparison with matched general population was performed using 2008 US life tables.

• Incremental risk factors for mortality were identified from 102 possible risk factors.

Patient Characteristics (1)

No. (%) or Mean ± SD

Demographics

Female 134 (43)

Age (y) 84 ± 6.3

Body Mass Index (kg/m2) 27 ± 5.7

Symptoms

NYHA Class 3 or 4 297 (95)

Predicted operative mortality

By benchmark available attime of enrollment (%)

12 ± 3.4

Cardiac Comorbidities

Coronary Artery Disease 241 (77)

Previous MI 90 (29)

Atrial Fibrillation 69 (22)

Patient Characteristics (2)

No. (%) or Mean ± SD

Non-Cardiac Comorbidities

Peripheral Arterial Disease 210 (67)

CVD 108 (35)

Diabetes 128 (41)

Chronic Pulmonary Disease 147 (47)

Renal Disease 69 (22)

Hepatic Disease 9 (2.9)

Previous Procedures

PCI 101 (32)

CABG 140 (45)

Pacemaker 70 (22)

Echocardiographic Characteristics

AV peak velocity (cm/sec) 422 ± 70

AV area (cm2) 0.64 ± 0.19

AV mean gradient (mmHg) 43 ± 14

Ejection fraction (%) 53 ± 12

Operative Details / Variables (1)

No. (%) or Mean ± SD

Incision

Full sternotomy 243 (78)

Partial sternotomy 51 (16)

Thoracotomy 18 (5.8)

Aortic valve prosthesis

Valve size (mm)

19 37 (12)

21 124 (40)

23 109 (35)

25 37 (12)

27 3 (0.97)

Operative Details / Variables (2)

No. (%) or Mean ± SD

Prosthesis type

Edwards Lifesciences 273 (87)

St. Jude 3 (0.95)

Carbomedics mechanical 4 (1.3)

Medtronic 12 (3.8)

Sorin 7 (2.2)

Unspecified porcine 1 (0.32)

Unspecified 13 (4.2)

Concomitant procedure

Unanticipated CABG 21 (6.7)

Support

Aortic clamp time (min) 74 ± 29

Cardiopulmonary bypass time (min) 105 ± 41

Outcome Referenced to Contemporary STS Benchmarks

OutcomeObserved

No. (%)ExpectedNo. (%)

Observed/Expected(68% CL) p

Operative mortality 33 (10) 29 (9.3) 1.14 (1.01 – 1.29) 0.40

Stroke 8 (2.6) 11 (3.5) 0.73 (0.55 – 0.94) 0.40

Renal Failure 18 (5.8) 38 (12) 0.48 (0.38 – 0.60) 0.0008

Deep sternalwound infection

2 (0.64) 1.03 (0.33) 1.94 (0.91 – 3.1) 0.30

Postoperative lengthof stay > 14 days

83 (26) 56 (18) 1.48 (1.36 – 1.62) <0.0001

OutcomeObserved

No. (%)ExpectedNo. (%)

Observed/Expected(68% CL) p

Operative mortality 33 (10) 29 (9.3) 1.14 (1.01 – 1.29) 0.40

Stroke 8 (2.6) 11 (3.5) 0.73 (0.55 – 0.94) 0.40

Renal Failure 18 (5.8) 38 (12) 0.48 (0.38 – 0.60) 0.0008

Deep sternalwound infection

2 (0.64) 1.03 (0.33) 1.94 (0.91 – 3.1) 0.30

Postoperative lengthof stay > 14 days

83 (26) 56 (18) 1.48 (1.36 – 1.62) <0.0001

20

40

60

80

100

0 1 2 3 4

%

Years

Worse Survival Compared to Age Matched Population

SAVR

Incremental Risk Factors for Mortality after SAVR

Risk Factor Coefficient ± SE pHazard Ratio

(68% CL)Reliability

(%)a

Early decreasing hazard

Previous CABG (less risk) -0.57 ± 0.29 0.03 0.57 (0.42 – 0.76) 88

Lower albuminb 7.0 ± 3.4 0.05 n/a 51

Longer aortic clamp timec 0.95 ± 0.36 0.009 n/a 60

Intermediate-term hazard

Smaller BMId 0.99 ± 0.39 0.01 n/a 64

History of cancer 0.86 ± 0.31 0.006 2.4 (1.7 – 3.2) 59

Severe prosthesis-patient mismatch 0.77 ± 0.27 0.004 2.2 (1.6 – 2.8) 86

a. Percent of times variables appeared in 1000 bootstrap modelsb. (1/albumin), inverse transformationc. Log (aortic clamp time/75), logarithmic transformationd. (25/BMI)2, inverse squared transformation

20

40

60

80

100

0 1 2 3 4

%

Years

Prior CABG

Yes

No

Survival

1 Year Survival - Albumin

65

70

75

80

2.5 3.0 3.5 4.0 4.5Albumin (g/dL)

Su

rviv

al (%

)

65

70

75

80

40 60 80 100 120 140 160Aortic Clamp Time (min)

Su

rviv

al (%

)1 Year Survival - Aortic Clamp Time

1 Year Survival - BMI

65

70

75

80

15 20 25 30 35 40Body Mass Index

Su

rviv

al (%

)

20

40

60

80

100

0 1 2 3 4

%

Years

Cancer

No

Yes

Survival

20

40

60

80

100

0 1 2 3 4

%

Years

Mismatch

None/Mild

SevereModerate

Survival

20

40

60

80

100

0 1 2 3 4

%

Years

SAVR

Medical Therapy

Survival: SAVR vs Medical Therapy

20

40

60

80

100

0 1 2 3 4

%

Years

SAVR

Medical Therapy

Survival

Age = 70BMI = 36Albumin = 2.9Cancer

20

40

60

80

100

0 1 2 3 4

%

Years

Medical Therapy

SAVR

Survival

Age = 90BMI = 27Albumin = 3.04Cancer

20

40

60

80

100

0 1 2 3 4

%

Years

Medical Therapy

SAVR

Survival

Age = 86BMI = 21CancerPrevious CABG

Conclusions (1)

• PARTNER 1A SAVR outcome was similar to contemporary benchmarks, suggesting these benchmarks may underestimate risk across high risk profiles.

• PARTNER 1A SAVR patients had worse survival compared to matched US population, suggesting a less selected population with higher morbidities and risk profile.

Conclusions (2)

• PARTNER 1A SAVR patients have improved survival compared to PARTNER 1B patients randomized to medical therapy, although a few selected risk profiles demonstrated the futility of SAVR with worse outcome.

• PARTNER selection criteria for SAVR may be more appropriate and realistic, thus reflecting the contemporary surgical management of severe aortic stenosis in high risk patients.

Thank you to the dedicated study teams at all the PARTNER Sites!

Special thanks to the participants in this writing groupLars G. Svensson

Jeevanantham Rajeswaran

John Ehrlinger

Rakesh M. Suri

Craig R. Smith

Michael Mack

D. Craig Miller

Patrick M. McCarthy

Joseph E. Bavaria

Lawrence H. Cohn

Paul J. Corso

Robert A. Guyton

Vinod H. Thourani

Bruce W. Lytle

Mathew R. Williams

John G. Webb

Samir Kapadia

E. Murat Tuzcu

David J. Cohen

Hartzell V. Schaff

Martin B. Leon

Eugene H. Blackstone