CoreValve US Pivotal Extreme RiskGeorge Petrossian, MD For the CoreValve US Clinical Investigators. Disclosures Medtronic personnel performed all statistical analyses and assisted

Clinical Outcomes at 5 Years Following Self-Expanding Transcatheter Aortic Valve Replacement in the CoreValve US Extreme Risk Pivotal Trial

George Petrossian, MDFor the CoreValve US Clinical Investigators

Disclosures

Medtronic personnel performed all statistical analyses and assisted in the graphical display of the data.

• There are patients suffering from severe, symptomatic aortic stenosis in which the potential for harm due to surgical aortic valve replacement outweighs the potential for benefit. Reasons include frailty, comorbidity, disability, or anatomical characteristics that preclude operation.

• These were the subjects in the CoreValve US Extreme Risk Pivotal Trial, which evaluated the clinical safety and efficacy of the self-expanding Medtronic CoreValve transcatheter aortic valve replacement (TAVR) system.

• The trial met its primary endpoint at 1 year, demonstrating that treatment with TAVR reduced the frequency of all-cause mortality or major stroke compared with an objective performance goal (26.0% vs. 43.0%; p<0.0001). With this, CoreValve received an FDA-approved indication in patients at extreme surgical risk.

• The 5-year follow-up for the trial is now complete, and the clinical outcomes are presented here.

Background

• Patients:

– Severe, symptomatic AS was defined as at least NHYA class II symptoms, an aortic valve area ≤0.8 cm2 (or aortic valve index ≤0.5 cm2/m2), and a mean aortic valve gradient >40 mmHg or a peak aortic valve velocity >4.0 m/s were eligible

– Extreme risk was characterized as 50% or greater risk for mortality or irreversible morbidity at 30 days with surgical replacement

• Design and Analysis:

– Prospective, multicenter, controlled, non-randomized, and single-arm, performed at 41 centers in the US

– The attempted iliofemoral implant population was the primary analysis group

Methods

CoreValve US Pivotal Trial

Extreme Risk High Risk

CoreValveIliofemoral

N=489

Iliofemoral Access > 18 Fr Sheath Randomization 1:1

CoreValveNon-Iliofemoral

N=150CoreValve SAVR

Pivotal Trial Design

Subject Disposition

Roll-in subjects = 63

Attempted implant via NIF = 150Exited prior to procedure = 17

Died = 121Study Exit = 1

Patients at 2 YearsN=307




Subjects EnrolledN=710

Eligible SubjectsN=656

Attempted Iliofemoral ImplantN=489

Patients at 1 YearN=367





91.8% Follow-up (n=156/170)

91.6% Follow-up (n=219/239)

97.6% Follow-up (n=121/124)

94.1% Follow-up (n=289/307)

99.2% Follow-up (n=364/367)

100% Follow-up (n=489/489)

98.2% Follow-up (n=442/450)

Study ComplianceClinical Assessments

BaselineN=489

1 MonthN=450

2 YearsN=307

1 YearN=367

3 YearsN=239

4 YearsN=170

5 YearsN=124

Baseline DemographicsCharacteristic, % N=489Age, years 83.2 ± 8.7Male sex 48.1STS Predicted Risk of Mortality 10.3 ± 5.5New York Heart Association class III/IV 91.8

Diabetes mellitus 41.5

Prior stroke 13.7

Peripheral vascular disease 35.2

Coronary artery disease 81.8

Prior myocardial infarction 30.9

Prior coronary artery bypass grafting 39.5

Prior percutaneous coronary intervention 37.0

Atrial fibrillation / atrial flutter 46.8

Pre-existing permanent pacemaker or ICD 26.0

Comorbidities, Frailty, Disabilities

Characteristic, % or mean ± st dev N=489

Prohibitive Anatomy

Chest wall deformity 5.5

Hostile mediastinum 11.9

Comorbidities

Charlson comorbidity score 5.3 ± 2.3

Home oxygen 29.9

Frailty

Falls in past 6 months 18.0

5 meter gait speed > 6 secs 84.2

Disabilities

Assisted living 27.6

Wheelchair bound 16.6

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5

All-C

ause

Mor

talit

y or

Maj

or S

trok

e

Years Post-Procedure

All-Cause Mortality or Major Stroke

489 361 302 229 167 96

No. at Risk

71.7%

51.3%P < 0.0001Performance Goal = 43%

26.0%[22.1,29.9]

Secondary Endpoints

* Percentages are Kaplan Meier estimates.

Events*, % 1 Year 3 Years 5 Years

All-cause mortality 24.3 49.6 70.9

Cardiovascular mortality 18.3 35.3 55.0

Any stroke 7.0 13.4 15.4

Major 4.3 8.7 10.7

Minor 3.2 6.3 6.8

Myocardial infarction 2.0 3.9 5.1

Reintervention 1.8 1.8 2.7

Aortic valve hospitalization 21.6 35.6 48.4

Valve thrombosis 0.0 0.0 0.0

Valve endocarditis 1.0 1.3 2.1

Effe

ctiv

e O

rific

e Ar

ea, c

m2 M

ean Gradient, m

m Hg0.67

1.66 1.681.75 1.71

1.79 1.8047.92

9.44 8.73 8.14 7.37 7.33 7.63

0

10

20

30

40

50

60

Baseline Discharge 1 Year 2 Years 3 Years 4 Years 5 Years0.0

0.4

0.8

1.2

1.6

2.0

Effective orifice area

Mean gradient

Echocardiographic FindingsSite-Reported

Gradient 484 458 336 261 185 123 93EOA 470 414 308 246 173 110 82

NYHA Class

34.9%

58.7%50.0% 51.5%

8.7%

47.4%

32.5%34.7% 38.4%

64.7%

17.0% 7.3% 13.7% 10.1%26.6%

0.7% 1.5% 1.6%

0%

20%

40%

60%

80%

100%

Baseline(N=485)

30 Days(N=430)

1 Year(N=341)

3 Years(N=190)

5 Years(N=99)

% o

f Pat

ient

s

NYHA I NYHA II NYHA III NYHA IV

37.9

68.8 67.0 64.3

0

10

20

30

40

50

60

70

80

90

100

BaselineN=455

1 YearN=266

3 YearsN=147

5 YearsN=85

KCCQ Overall Summary ScoreChange from Baseline

Differences and p-values based on paired t-test compared with baseline

Δ = 27.8P<0.001

Δ = 25.0P<0.001

Δ = 21.2P<0.001

CoreValve Baseline

Total Aortic RegurgitationSite Reported

25.8% 22.1%32.3%

46.0% 45.2%

66.4% 71.2%61.0%

48.7% 49.5%

7.3% 6.7% 6.3% 4.8% 4.3%0.4% 0.5% 1.1%

0%

20%

40%

60%

80%

100%

Discharge(N=453)

30 Days(N=430)

1 Year(N=334)

3 Years(N=189)

5 Years(N=93)

% o

f Eva

luab

le E

choc

ardi

ogra

ms

None Mild Moderate Severe

• At 5 years, the CoreValve US Pivotal Extreme Risk Study showed:

– Approximately 30% of patients with an attempted implant survived. Non-cardiovascular causes drove 30% of the deaths, highlighting the complex baseline clinical status of the patients.

– The improvement in effective orifice area and reduction in aortic valve gradient was stable over time. There were no cases of valve thrombosis.

– The improvement in symptoms and quality of life was durable for the patients surviving to 5 years.

Conclusions

Thank YouOn Behalf of the CoreValve US Investigators

Extras

5-Year Mortality

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5

Mor

talit

y


All-Cause

Cardiovascular

489 369 309 237 171 99No. at Risk

55.0%

18.3%

35.3%

70.9%

24.3%

49.6%

No. at Risk

0%

5%

10%

15%

20%

25%

30%

0 1 2 3 4 5

Stro

ke


AllMajor

Stroke

489 350 288 215 157 92489 361 302 229 167 96

15.4%

7.0%

13.4%

10.7%

4.3%

8.7%

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5

Aort

ic V

alve

Hos

pita

lizat

ion


Aortic Valve Hospitalization

489 311 253 181 120 64No. at Risk

48.4%

21.6%

35.6%

0%

5%

10%

15%

20%

25%

30%

0 1 2 3 4 5

Rein

terv

entio

n


Reintervention

489 365 305 235 169 97No. at Risk

2.7%1.8% 1.8%

No Pacemaker within 30 Days 346 251 213 165 122 72

New 30-Day Pacemaker 128 93 78 57 42 21

Inbound Pacemaker 165 121 100 78 57 32

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5

All-C

ause

Mor

talit

y


No Pacemaker within 30 Days

New 30-Day Pacemaker

Inbound Pacemaker

Mortality by Permanent Pacemaker

No. at Risk

P-value (log-rank) =0.93

71.9%73.0%

70.8%

27.3%

26.7%

27.2%

51.3%51.1%

50.7%

None/Trace 283 227 193 150 109 62Mild 228 163 132 101 76 45Moderate 64 49 41 30 22 11Severe 8 1 1 1 1 0

Mortality by Total Aortic RegurgitationAR assessed at Discharge

0%

20%

40%

60%

80%

100%

0 1 2 3 4 5

All-C

ause

Mor

talit

y


None/Trace

Mild

Moderate

Severe

No. at Risk

P-value (log-rank) <0.0001

100%

73.4%73.2%67.1%

87.5%

28.5%23.4%

19.4%

87.5%

54.1%50.6%

44.4%

Documents

CoreValve US Pivotal Extreme RiskGeorge Petrossian, MD For the CoreValve US Clinical Investigators. Disclosures Medtronic personnel performed all statistical analyses and assisted