COREVALVE™ AND EVOLUT™ R TAVI SYSTEMSSURTAVI CLINICAL TRIAL RESULTS

INTERNATIONALCAUTION: For distribution only in markets where CoreValve Evolut R intermediate risk indication has been approved. CoreValve System is not approved for Intermediate Risk Patients.

Refer to Instructions for Use for a complete list of warnings, precautions, indications and contraindications.

A Groundbreaking Study of Intermediate Risk Symptomatic Severe Aortic Stenosis Patients

STUDY BACKGROUND AND DESIGN

The SURTAVI Clinical Trial is a prospective, multinational, randomized clinical trial evaluating the CoreValve™ and Evolut™ R systems vs. surgery in patients with symptomatic severe aortic stenosis at intermediate surgical risk. The primary objective was to show that TAVI is noninferior to SAVR.

n 1660 patients (mITT)n 87 sites in US, Canada and Europen CoreValve system and Evolut R system evaluated

PATIENT FLOW

1746 patients

randomized

TAVI ITT group:

N=879

SAVR ITT group:

N=867

TAVI mITT GROUP: N=864

SAVR mITT GROUP: N=796

TAVI implanted

group: N=863

SAVR implanted

group: N=794

ITT: intention-to-treat population consisted of all randomized subjects (n=1746)

mITT: modified intention-to-treat population consisted of all ITT subjects with an attempted implant procedure (n=1660)

CoreValve TAVI: 23, 26 and 29 mm (all sites)

US: Evolut R TAVI: 23, 26 and 29 mm

EU/CAN

CoreValve TAVI: 31 mm (all sites)

84%

16%

2012 2013 2014 2015 2016

DEC 2016

JUNE 2012

APRIL 2015

JUNE 2016

STUDY DEVICE INCLUSION TIMELINE

CoreValve TAVI (n=724)

PRIM

ARY

EN

DPO

INT

AS

SE

SS

ME

NT

Enrollment completedFirst patient enrolled

Evolut R TAVI (n=139)

Evolut™ R TAVI in US

The majority of TAVI patients were treated with the CoreValve device.

STUDY ENDPOINTS Primary Endpoint n All-cause mortality or disabling

stroke at 24 months

Secondary Endpoints Safety n All-cause mortality n All stroke n Aortic valve reintervention n Major vascular complications n Life-threatening or major bleeding n Pacemaker implantation n MACCE

Efficacy n Mean gradient n EOA n Moderate/severe AR

Quality of life n KCCQ

KEY INCLUSION CRITERIAn Severe aortic valve stenosis defined by an initial

aortic valve area of ≤1.0 cm² or aortic valve area index <0.6 cm2/m2, AND a mean gradient >40 mmHg or Vmax > 4m/sec, at rest or with dobutamine provocation in patients with a LVEF < 55%, or Doppler Velocity Index <0.25 by resting echocardiogram

n Heart team agreement that predicted 30-day surgical mortality risk is ≥3% and <15% based on STS PROM and overall clinical status including frailty, disability and comorbidity factors

n NYHA functional class II or greater

STUDY BACKGROUND AND DESIGN

n (%) or mean ± SDTAVI

(N=864)SAVR

(N=796)

Age, years 79.9 ± 6.2 79.7 ± 6.1

Body surface area, m2 1.9 ± 0.2 1.9 ± 0.2

Male sex 498 (57.6) 438 (55.0)

STS PROM, % 4.4 ± 1.5 4.5 ± 1.6

Logistic EuroScore, % 11.9 ± 7.6 11.6 ± 8.0

Diabetes mellitus 295 (34.1) 277 (34.8)

Serum Creatinine >2 mg/dl 14 (1.6) 17 (2.1)

Peripheral vascular disease 266 (30.8) 238 (29.9)

Prior stroke 57 (6.6) 57 (7.2)

Prior TIA 58 (6.7) 46 (5.8)

Prior CABG 138 (16.0) 137 (17.2)

Permanent pacemaker 84 (9.7) 72 (9.0)

BASELINE CHARACTERISTICS1

1 mITT population

KEY EXCLUSION CRITERIA (additional criteria may apply)n Any PCI or peripheral

intervention within 30 days of randomization

n Multivessel CAD with Syntax score >22

n Unsuitable anatomy including native aortic annulus <18 mm or >29 mm

n Congenital bicuspid or unicuspid valve verified by echo

SAFETY AND PERFORMANCE

The SURTAVI trial further supports the safety and performance of the Evolut R system in treating intermediate risk patients.

All-

caus

e M

orta

lity

or D

isab

ling

Stro

ke

555674796 407 241 612755864

SAVRNo. at Risk

TAVI 456 272

Months Post-Procedure

0%

5%

10%

15%

20%

25%

30%

1260 18 24

SAVR TAVI

ALL-CAUSE MORTALITY OR DISABLING STROKECoreValve and Evolut R systems demonstrated non-inferiority against an exceptional surgical cohort.

NOTE: The SURTAVI study utilized a novel Bayesian statistical methodology. A subset of the cohort had complete data at 24 months. The remaining subjects have incomplete data at various intervals in the follow-up. The data from the “completers” was used to model out the probable result for the study by simulating results for the non-completers using their status at their last known interval.

The numerical comparisons made throughout the study and this data summary are the posterior median rates modeled by the Bayesian analysis. The Kaplan-Meier curves are also included, and patients are censored from the analysis at the last point of the follow-up as is the convention with Kaplan-Meier analyses.

Bayesian Analysis: 24-month all-cause mortality or disabling stroke

TAVI SAVR

12.6% 14.0%

1.2% 30-DAY DISABLING STROKE RATE FOR

TAVI ARM

Dis

ablin

g St

roke

0%

2%

4%

6%

8%

10%

1260 18 24

555674796 407 241 612755864

SAVRNo. at Risk

TAVI 456 272

SAVR TAVI

Months Post-Procedure

LOW RATES OF DISABLING STROKE

STRONG SAFETY AND PERFORMANCE

Bayesian Analysis: 24-Month Disabling Stroke

TAVI SAVR 95% Cl for Difference

2.6% 4.5% -4.0, 0.1

Data modeled by the Bayesian analysis

*Post-Procedure/Discharge

3.45.6

12.5

41.1

0.73.5

6.0

1.1

25.9

6.63.8

1.1

43.4

12.9

4.41.7

30-D

ay S

afet

y O

utco

mes

(%)

0%

10%

20%

30%

40%

50%

TransfusionUse

All-stroke

AtrialFibrillation

Moderate/SevereAortic

Regurgitation*

AcuteKidneyInjury

MajorVascular

Complications

CardiogenicShock

PermanentPacemaker

Implant

TAVI SAVR

SIGNIFICANTLY BETTER FOR TAVI

SIGNIFICANTLY BETTER FOR SAVREXCELLENT EARLY

OUTCOMESAt 30 days, TAVI was superior to SAVR in several key areas, including all-stroke, atrial fibrillation and acute kidney injury.

5.75

9.75Le

ngth

of H

ospi

tal S

tay

(Day

s)

0

5

10

15

20

SAVRTAVI

FASTER RECOVERY WITH TAVI

SHORTER HOSPITAL STAYSTAVI associated with significantly earlier hospital discharge than SAVR.

SAVR TAVI

40

60

80

100

Baseline 30 Days 6 Months 12 Months

Change From TAVI 18.4 ± 22.8 21.8 ± 22.3 20.9 ± 22.2Baseline SAVR 5.9 ± 27.0 21.3 ± 22.3 20.6 ± 22.2 95% Cl for difference (10.0, 15.1) (-1.9, 2.8) (-2.2, 2.9)

KCC

Q S

core

FASTER FUNCTIONAL RECOVERYHigher quality of life scores at 30 days in the TAVI group.

*Core lab adjudicated

TAVI had significantly better valve performance over SAVR at all follow-up visits

SIGNIFICANTLY BETTER HEMODYNAMICS* The supra-annular design of the Core-Valve and Evolut R valves provides excellent hemo-dynamic perform-ance with large, stable EOA and low single digit gradients.

SAVR TAVI

Effec

tive

Ori

fice

Are

a, c

m2

0.0

0.5

1.0

1.5

2.0

2.5

Baseline Discharge 6 Months 1 Year 2 Years0.0

Mean G

radient, mm

Hg

10.0

20.0

30.0

40.0

50.0

60.0

47.8

12.4 11.1 11.7 11.8

1.82

0.77

1.79 1.76 1.68

47.2

0.78

2.13 2.15 2.15 2.19

8.9 8.3 8.3 7.8

UNSURPASSED HEMODYNAMICS

STUDY SUMMARY

SURTAVI met its primary endpoint demonstrating that TAVI with CoreValve and Evolut R systems is non-inferior to SAVR for all-cause mortality or disabling stroke at 24 months

The SAVR arm performed exceptionally well, with an extremely low observed to expected surgical mortality ratio at 30 days

At 30 days, TAVI was associated with significantly lower rate of all-stroke vs. SAVR

At 30 days, TAVI had lower rates of acute kidney injury and atrial fibrillation, while SAVR had lower rates of major vascular complications and new permanent pacemaker

TAVI resulted in significantly lower mean gradients and greater aortic valve areas than SAVR at all post-implant time points

Functional recovery times were faster and hospital stays were shorter for patients treated with TAVI

1

2

3

5

4

6

THE CHOICE FOR INTERMEDIATE RISK PATIENTS

Designed for durability, the Evolut R system addresses anatomic and procedural challenges in patients with symptomatic severe aortic stenosis.

7.8mmHg SINGLE DIGIT GRADIENTS

2.2cm2 LARGE EOA

Commissure height and deep leaflet cuts minimize leaflet stress

Self-expanding nitinol frame conforms to varying annular anatomy

Unsurpassed hemodynamics at 24 months:

Supra-annular valve design provides optimal leaflet mounting and coaptation

INTERNATIONALCAUTION: For distribution only in markets where Evolut R intermediate risk indication has been approved. CoreValve System is not approved for Intermediate Risk Patients.

Refer to Instructions for Use for a complete list of warnings, precautions, indications and contraindications.

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