MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet Study of Access For Enhancement of STEMI for Seniors: The SAFE STEMI for Seniors Protocol Mitchell W. Krucoff, MD, FACC Professor, Medicine/Cardiology Duke University Medical Center Director, Cardiovascular Devices Unit Director, MDEpiNet Coordinating Center Duke Clinical Research Institute MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet

Disclosure Statement of Financial Interest 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 Grant/Research Support Consulting Fees/Honoraria Major Stock Shareholder/Equity Royalty Income Ownership/Founder Intellectual Property Rights Other Financial Benefit Company Names

Conflicts No personal stock, holdings or IP No corporate revenue >$50k per annum Research grants, consulting relationships: Abbott Vascular Acist Medical Biosensors Boston Scientific Cook Medical Cordis J&J CSI Medtronic OrbusNeich St. Jude Medical Terumo

MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet What is SAFE STEMI for Seniors? Combining public health and regulatory science A new approach to STEMI in seniors: 100% STEMI, 100% “radial first” strategy Prospective RCT: IRA-only vs. complete revasc A new approach to medical device trials: Registry-based randomized trials: less site based work load faster enrollment More efficient regulatory decisions: complementary clinical questions for labelling (IDE) partnered manufacturer-sponsors MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet

Why SAFE STEMI for Seniors? SENIORS: The Role of Age in STEMI Complications from STEMI: Highest mortality Highest MACE rates Complications from therapies: Bleeding rates Vascular complications Other peri-procedural complications Complications with billable (Medicare) services Claims data documentation MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet

Ready for prime time? Ready for seniors? …..in the USA??? “Radial-first” STEMI Ready for prime time? Ready for seniors? …..in the USA??? MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet

RIVAL: 5,063 non-STEMI, 1,958 STEMI RIFLE STEACS: 1,000 STEMI MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet Jolly SS et al Lancet 2011 Romagnoli E et al JACC 2013

MATRIX: ACS (STEMI & Non-STEMI) MACE NET DEATH 8,404 patients RCT TRI vs TFI Numerically lower MACE & mortality Significantly lower Net clinical benefit BARC Valmigli M et al, Lancet 2015;385:2465-76

MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet Novel Trial Structure 21st Century Regulatory Science: Registry-based randomized trials The NEST Context MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet

MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet National Evaluation System for Health Tech (NEST) Real World Evidence of Device Benefit/Risk, Safety Krucoff MW, Normand SL et al, JAMA 2015 Shuren J, Califf R, JAMA Published online July 11, 2016 MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet

TCT 2013 Featured LBCT A Registry-Based Randomized Trial Comparing Radial and Femoral Approaches In Women Undergoing Percutaneous Coronary Intervention: The Study of Access Enhancement of PCI for Women (SAFE-PCI for Women) Trial Sunil V. Rao MD, Connie N. Hess MD, Britt Barham, Laura H. Aberle, Kevin Anstrom PhD, Tejan B. Patel MD, Jesse P. Jorgensen MD, Ernest L. Mazzaferri MD, Sanjit S. Jolly MD, Alice Jacobs MD, L. Kristin Newby MD, C. Michael Gibson MD, David F. Kong MD, Roxana Mehran MD, Ron Waksman MD, Ian C. Gilchrist MD, Brian J. McCourt, Eric D. Peterson MD MPH, Robert A. Harrington MD, Mitchell W. Krucoff MD on behalf of the SAFE-PCI for Women Investigators

SAFE-PCI for Women workflow Randomization Demographics Medical Hx Procedural data Index Hosp MACE Autopopulate Part 11 Compliant 65% site coordinator workload reduction Unique pages for trial Analytic Database

Efficiency Accelerates Enrollment

MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet September 2013 Lauer M et al, NEJM 2013 Hess C et al, Am Heart J 2013 MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet Rao S et al JACC Cardiovascular Int 7(8)2014

SAFE STEMI for Seniors: Study Design IDE

Patient Flows IDE MV PCI in STEMI PRAMI CvLPRIT

SAFE STEMI for Seniors: Linked NCDR-Claims Data “CRN” Structure Index Procedure Clinical Follow-up: Administrative Data n=1,000 Safety evaluation of Edwards Sapien heart valve in general practice Follow-up to 5 years: Detailed registry follow-up for year 1 Medicare claims follow-up for full time interval Comparator: Objective Performance Criteria (OPC) based on prior trial data Innovations in Efficient follow-up for post-market studies: Algorithm-assisted endpoints Medicare linkage This study will require patient-level consent because of the need for additional clinical follow-up that was considered outside the standard of care. 2 Registry-sponsored observational IDE studies are under review with FDA for label extension. These were designed to only include ‘standard of care’ clinical follow-up & may not require individual patient-level consent. CRF data from Clinical Registry Index AMI Hospitalization 1mo 1 yr 2 yrs 3 yrs 4 yrs 5 yrs Months

SAFE STEMI for Seniors: Conclusions Public health clinical trial: Radial access PCI in seniors Multivessel PCI in seniors Partnered manufacturer IDE: DES labelling for STEMI (Medtronic) iFR guided multivessel PCI (Volcano-Philips) 21st Century regulatory science Registry-based (CRN) RCT: Index procedure (NCDR Cath-PCI) Long term follow up (Claims data) MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet

What is SAFE STEMI for Seniors? Public health clinical trial: >65 y.o STEMI <6 hrs Radial access PCI in seniors Multivessel PCI in seniors IDE(s) clinical trial: DES labelling for STEMI (Medtronic) iFR guided multivessel PCI (Volcano-Philips) Registry-based CRN randomized trial: Index procedure (NCDR Cath-PCI) Long term follow up (Claims data) Lesson in partnered problem solving MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet

MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet Study of Access For Enhancement of STEMI for Seniors: The SAFE STEMI for Seniors Protocol Mitchell W. Krucoff, MD, FACC Professor, Medicine/Cardiology Duke University Medical Center Director, Cardiovascular Devices Unit Director, MDEpiNet Coordinating Center Duke Clinical Research Institute MDEpiNetMDEpiNet MDEpiNet MDEpiNetMDEpiNetMDEpinet