One Year Outcomes and Resource Utilization in ACRIN PA 4005: Multicenter RCT of Rapid Rule-Out Strategy of CCTA vs Tra

1. One Year Outcomes and Resource Utilization in ACRIN PA 4005:Multicenter RCT of Rapid Rule-Out Strategy of CCTA vs Traditional Care Judd E. Hollander, MD Professor Clinical Research Director

2. Funding & Disclosures • Funding • PA Department of Health (SAP4100042725). The Department specifically disclaims responsibility for any analyses, interpretations or conclusions. • American College of Radiology (ACR) Foundation • Organized & coordinated by ACRIN which receives funding from the National Cancer Institute (U01 CA079778 and U01 CA080098). • Other Research Funding • Abbott, Alere, Brahms, NIH, PCORI, Siemens • Consulting • Behring, Janssen, Luitpold, Radiometer

3. Introduction • Approximately 8 million ED visits for chest pain each year in the US • 60% admitted • 5-15% ACS rate • 85-95% do not have cardiac cause for symptoms • Historically, 2-5% missed AMI rate

4. Introduction • Conservative admission protocols • Cost $8-10 billion per year • Contributes to hospital crowding • Leads to adverse outcomes in other cohorts • May or may not help the “rule out” ACS patients • More efficient options desired

5. ED Specific Studies • Multiple small single arm studies • Hollander et al. • 500+ patient observational trial • ROMICAT 1 • 300+ patient observation trial • Small RCT’s • Goldstein, Gallagher • Larger RCT’s • CT STAT, ACRIN 4005, ROMICAT 2

6. ACRIN PA 4005 30-day Outcomes • Patients with negative CCTA can be safely discharged (0% event rate, 95%CI, 0.57) • CCTA more efficient • Higher discharge rate • More rapid discharge • More patients diagnosed with CAD (9 v 3%) • Higher rate of positive cardiac catheterization • No increased rate of revascularization • No difference in 30 day death or AMI

7. Objectives • To compare health care utilization during 1 year post-randomization • Imaging, intervention, repeat ED visits, re-admission • To compare major cardiac events during 1 year post randomization for participants not found to have CAD during index visit

8. Methods • Study design • Randomized controlled trial (CCTA 2:1) • Setting • 5 sites • Patient Enrollment • Not limited to times when testing available • Mostly in ED • Could be in observation before testing decision

9. Methods: Patients • Inclusion • > age 30 • TIMI score 0-2 • No ischemia on ECG • Exclusion • Clearly noncardiac pain • Comorbidity requiring admission • Contraindications to CCTA • Post randomization • CrCl < 60 or PE protocol CT done

10. Methods: Testing • CCTA • Noncontrast calcium scoring • Contrast angiography • B-blockers and NTG per local protocol • All readers ACC/AHA level 3 • Local interpretations used clinically • Stress testing • Imaging or not was a local decision

11. Methods: Data Collected • Standardized Guideline Core Criteria • History • Presence of chest pain at ED presentation • Associated symptoms • Initial ECG • TIMI risk score • Cardiac markers

12. Methods: Follow-up • Direct patient contact • Medical record review • Presenting institution • Neighboring institution • Home visits • SSDI

13. Methods: Outcomes • Resource utilization • Revascularization • Cardiac testing • ED visits • Re-admission • One year outcomes • Death • Adjudicated for cardiac cause • Nonfatal AMI • Adjudicated

14. Results: Patient Characteristics

15. One Year Safety • Enrollment through one year

16. One Year Safety • Patients not found to have CAD

17. One Year Resource Use • After Hospital Discharge

18. Stratified by CAD

19. Discussion • Coronary CTA is accurate • Compares well to cardiac catheterization • Normal or minimal disease on cath • Predicts freedom from events at 30 days • A negative CCTA (<50% maximal stenosis) predicts freedom from events at one year

20. Discussion • In the year following discharge there was no increase in resource utilization • Diagnostic testing for CAD • Echocardiogram • Medication use • But resources applied more appropriately since patients more likely to have determination of underlying disease

21. Limitations • Powered off primary aim • UL of 95% CI being less than one percent in patients with negative CCTA • Cannot exclude possibility that we did not detect small but real difference between groups

22. Conclusions • A negative CCTA predicts low risk of 1 year death, AMI or revascularization • CCTA does not increase resource utilization • Shifts resources to where they are most useful • More disease identified and treated • More patients without disease not treated

23. Acknowledgements • Hospital of the University of Pennsylvania • Site Investigators: Judd E. Hollander, MD Harold I. Litt, MD, PhD • Research Coordinators: Emily Barrows, Jeffrey Le, Shannon Marcoon, Julie Pitts, RN, Scott Steingall, RT • Penn State University Medical Center at Hershey • Site Investigators: James M. Leaming, MD, Harjit Singh, MD, Michelle A. Fischer, MD, Steven Ettinger, MD, Carlos Jamis-Dow, MD, Kevin Moser, PhD • Research Coordinators: Swati Shah, Kevin Gardner, RN, Russell Dicristina, Susan Oskorus • Penn Presbyterian Medical Center • Site Investigators: Laurence Gavin, MD, Anna Marie Chang, MD • Research Coordinators: Christopher Decker, Michael Green, Katie O’Conor, Angela Roach, Kristy Walsh, Max Wayne

24. Acknowledgements • Wake Forest University • Site Investigators: J. Jeffrey Carr, MD, MSc, Daniel W. Entrikin, MD, Kim Askew, MD, James W. Hoekstra, MD, Simon Mahler, MD, Chadwick D. Miller, MD, MS • Research Coordinators: Denise Boyles, Stephanie Bradshaw, Mark Collin, Erin Harper, Lisa Hinshaw, MS, Jane Kilkenny, Megan Koonts, Lori Triplett, RN • University of Pittsburgh Medical Center • Site Investigators: Charissa B. Pacella, MD, Joan M. Lacomis, MD and Christopher R. Deible, MD, PhD • Research Coordinators: Sara Vandruff, Barbara Early, Tina Vita, Dawn McBride • Brown University: Biostatistical/research design • Constantine Gatsonis, PhD, Brad Snyder, MS, SanaaBoudhar, MS, Patricia Fox, MS and Erin Greco, MS

25. Acknowledgements • Data Safety Monitoring Board • David Bluemke, MD, PhD (Chair), National Institute of Health; Todd A. Alonzo, PhD, University of Southern California; Jon F. Merz, MBA, JD, PhD, University of Pennsylvania; Herbert Y. Kressel, MD, Beth Israel Deaconess Medical Center. • Adjudication Committee • W. Frank Peacock, MD, Cleveland Clinic; Robert Hendel, MD, University of Miami • Administration and Oversight – ACRIN PA • Cynthia Olson, Anthony Levering, Cynthia Price, Maria Oh, Patricia Blair, Martha Heckl, Charles Apgar, Mary Kelly, Mitchell Schnall MD, PhD