UC201300969c EN. Through Medtronic sponsored research, the Transcatheter Aortic Valves clinical portfolio is studying over 11,000 subjects at over 125.

UC201300969c EN

Through Medtronic sponsored research, the Transcatheter Aortic Valves clinical portfolio is

studying over 11,000 subjects at over 125 clinical sites worldwide, we are committed to providing industry-leading transcatheter therapy clinical

research evidence.

These materials are provided strictly for you to familiarize yourself with the TAVI clinical research portfolio. CAUTION – Investigational device. Limited by United States law to investigational use. CoreValve is not approved in the USA or Japan. © 2013 Medtronic, Inc.

Building a Comprehensive Portfolio

Demonstrate Safety and Efficacy

Expand Access to New Populations and Markets

Confirm Efficacy and Optimize Practice


CoreValve® ADVANCE Study• ADVANCE is a rigorous, fully monitored

study of TAVI in the “real world.” • 1,015 Subjects intended to be treated

with the Medtronic CoreValve System were enrolled at 44 centers (in 12 countries -Western Europe, Asia and South America).

• All primary endpoints were adjudicated by an independent Clinical Event Committee. In addition, all cerebrovascular events were adjudicated by an independent neurologist.

• Clinical endpoints reported according to Valve Academic Research Consortium (VARC 1).


CoreValve® ADVANCE Study

Study StatusActive ongoing study

Subject Follow-up: ongoingSubjects Enrolled: 1,015Length Follow-up: 5-years

Primary EndpointMajor Adverse Cardiac & Cerebrovascular Events (MACCE) at

30-days post procedure.

MACCE defined as a composite of • All cause mortality• Myocardial Infarction (Q-wave and non-Q-wave)• Emergent cardiac surgery or percutaneous re-intervention• Stroke

Start Enrollment Complete 1-Month 6-Month 1-Year

ADVANCE March 2010



High Procedural Success

• Successful vascular access, delivery & deployment of device & successful retrieval of the delivery system (97.5%)

• No annular ruptures (0.0%)• Valve embolization (0.2%)• Conversion to open AVR (0.1%)• Coronary compromised (0.1%)

Significant Hemodynamic Improvements




Primary Endpoint

*Kaplan-Meier Estimates



Additional VARC 1 Endpoints

*Kaplan-Meier Estimates†New AKI that occurred outside of the 72 hr post-TAVI window are included

CoreValve® ADVANCE StudyLow stroke rate out to 1 year




CoreValve® US Pivotal Trial

• Evaluate the safety and efficacy of the Medtronic CoreValve® System in the treatment of symptomatic severe AS in subjects who are at high or extreme risk for aortic valve surgery

• Randomized open-label study conducted at 45 US sites


CoreValve® US Pivotal Trial


Subject Follow-up: ongoingSubjects Enrolled: ~1575Length Follow-up: 5-years

Primary EndpointsExtreme Risk: All-cause death or major stroke at 12 months

(compared to performance goal)High Risk: All-cause mortality at 12 months


US Pivotal Dec.2010

Extreme Risk enrollment complete

High Riskenrollment

complete


CoreValve® Continued Access Study

• Prospective, non-randomized, multicenter study.

• Enrolling up to 4,500 Subjects from 45 US centers. – 2,250 Extreme Risk – 2,250 High Risk


CoreValve® Continued Access StudyStudy Status

Active ongoing studySubjects Follow-up: ongoingSubjects Expected: 4,500Length Follow-up: 5-years

Primary EndpointExtreme Risk: All-cause mortality or major stroke at 12 months.

High Risk: All-cause mortality at 12 months


CONTINUEDACCESS

Feb.2012

currentlyenrolling



• Enrolling up to 550 Subjects from up to 45 US centers.

CoreValve® Expanded Use Study


CoreValve® Expanded Use Study


Subject Follow-up: ongoingSubjects Expected: 550Length Follow-up: 5-years

Primary EndpointAll-cause mortality or major stroke at 12 months.


ExpandedUse

Oct.2012

currently enrolling


CoreValve® SURTAVI Trial• Evaluate the safety and

efficacy of TAVI in Subjects with severe, symptomatic AS at intermediate surgical risk by randomizing Subjects to either SAVR or TAVI with the Medtronic CoreValve® System

• Enrolling approximately 2,500 Subjects randomized 1:1 to TAVI and SAVR in up to 75 European, Canadian, and US centers.


CoreValve® SURTAVI Trial


Subject Follow-up: ongoingSubjects Expected: ~ 2,500Length Follow-up: 5-years


SURTAVI Europe July

2012

USNov2012

currently enrolling

currentlyenrolling

Primary EndpointNon-inferiority of combined endpoint of all-cause mortality

and major stroke at 24 months.


CoreValve® ANZ Study


• Enrolling up to 900 Subjects from 10 centers in Australia and New Zealand.

• Independent Clinical Events Committee to adjudicate all major events

• Separate DSMB




Subject Follow-up: ongoingSubjects Expected: 900Length Follow-up: 2-years

Primary EndpointCardiac-related Mortality and Major Adverse Cardiac

and Cerebrovascular Events (MACCE) at 30 days.

Start Enrollment Complete 1-Month 1-Year 2-Year

ANZ Aug.2008

currentlyenrolling



High Procedural SuccessProcedure success was defined as successful implantation of the device, with no death or

conversion to surgery (98%)

* As of June 29, 2012. Enrollment ongoing.



* As of June 29, 2012. Enrollment ongoing.


CoreValve® ADVANCE II Study• Characterize current CoreValve

System implantation best practices

• Enrolled 200 Subjects in 9 European centers.


CoreValve® ADVANCE II StudyStudy Status

Active ongoing studySubject Follow-up: ongoingSubjects Enrolled: 200Length Follow-up: 6-months

Primary EndpointTo determine the incidence of new-onset class I or II indication for Permanent Pacemaker Implantation


ADVANCEII

Oct. 2011


CoreValve® ADVANCE DA Study• To further evaluate the clinical

benefit of TAVI via direct aortic access using the Medtronic CoreValve® System in Subjects with severe aortic stenosis.

• Prospective, interventional, single arm, post-market, multicenter study.

• Enrolling at least 100 Subjects in 13 European centers.

• Baseline, procedure, discharge, 30-days, 6-months & 12-months.


CoreValve® ADVANCE DA StudyStudy Status

Active ongoing studySubject Follow-up: not startedSubjects Expected: 100Length Follow-up: 1-year

Primary EndpointAll cause mortality at 30-days post procedure


ADVANCEDA

Oct.2012

currentlyenrolling


CoreValve® Japan Study


Subject Follow-up: ongoingSubjects Expected: 75 (total)Length Follow-up: 5-years

Primary EndpointEfficacy of the CoreValve system, changes in NYHA, and

EOA from baseline to 6 months.


Japan26/29 mm

Oct.2011

Japan23 mm

Oct2011

Currently Enrolling


CoreValve® Japan Study• Prospective, non-randomized, multicenter study • 4 centers in Japan

26mm and 29mm Valve Enrolled 55 Subjects

– Iliofemoral, subclavian , and direct aortic access to be studied

23mm Valve Separate study enrolling up to 31 Subjects

– Iliofemoral, subclavian , and direct aortic access to be studied


CoreValve® CE Pivotal Trial

Study StatusComplete

Subject Follow-up: 3-yearsSubjects Enrolled : 126Length Follow-up: 4-years

Primary EndpointsMajor Adverse Events at 30 days, and technical/procedure

success at discharge.

Start 1-Month 6-Month 1-Year 2-Years

CE Pivotal May2006



• Evaluate the safety and efficacy of the Medtronic CoreValve® System in the treatment of symptomatic severe AS in subjects who are at high or extreme risk for aortic valve surgery.

• Nonrandomized, prospective, observational study .

• 126 Subjects enrolled at 9 centers beginning in May 2006.

• Data collected at discharge, 30 days, 3 months, 6 months, and annually through 4 years.



Beginning Implant Success• Technical and procedural success (83.1%) • First experiences with the CoreValve device.

Functional Class Improvements80% of Subjects’ functional class improved after TAVI and remained stable out to 2 years.

Valve DurabilityNo incidence of structural valve deterioration out to 2 years.



Significant Hemodynamic Improvements


CoreValve® CE Pivotal TrialPre-procedural and post-procedural aortic valve regurgitation (AR)


CoreValve is a registered trademark of Medtronic CV Luxembourg S.a.r.l.


UC201300969c EN. Through Medtronic sponsored research, the Transcatheter Aortic Valves clinical portfolio is studying over 11,000 subjects at over 125.

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