Department of Emergency MedicineDepartment of Emergency Medicine

University of Pennsylvania Health SystemUniversity of Pennsylvania Health System

One Year Outcomes and Resource One Year Outcomes and Resource Utilization in ACRIN PA 4005:Utilization in ACRIN PA 4005:

Multicenter RCT of Rapid Rule-Out Strategy of Multicenter RCT of Rapid Rule-Out Strategy of CCTA vs Traditional Care CCTA vs Traditional Care

Judd E. Hollander, MDJudd E. Hollander, MDProfessorProfessor

Clinical Research Director Clinical Research Director

Funding & DisclosuresFunding & Disclosures FundingFunding

– PA Department of Health (SAP4100042725). The Department PA Department of Health (SAP4100042725). The Department specifically disclaims responsibility for any analyses, specifically disclaims responsibility for any analyses, interpretations or conclusions. interpretations or conclusions.

– American College of Radiology (ACR) FoundationAmerican College of Radiology (ACR) Foundation

– Organized & coordinated by ACRIN which receives funding from Organized & coordinated by ACRIN which receives funding from the National Cancer Institute (U01 CA079778 and U01 the National Cancer Institute (U01 CA079778 and U01 CA080098).CA080098).

Other Research FundingOther Research Funding– Abbott, Alere, Brahms, NIH, PCORI, SiemensAbbott, Alere, Brahms, NIH, PCORI, Siemens

ConsultingConsulting– Behring, Janssen, Luitpold, RadiometerBehring, Janssen, Luitpold, Radiometer

IntroductionIntroduction

Approximately 8 million ED visits for chest Approximately 8 million ED visits for chest pain each year in the USpain each year in the US– 60% admitted60% admitted– 5-15% ACS rate5-15% ACS rate

• 85-95% do not have cardiac cause for symptoms85-95% do not have cardiac cause for symptoms

– Historically, 2-5% missed AMI rateHistorically, 2-5% missed AMI rate

IntroductionIntroduction

Conservative admission protocolsConservative admission protocols– Cost $8-10 billion per yearCost $8-10 billion per year– Contributes to hospital crowdingContributes to hospital crowding– Leads to adverse outcomes in other cohortsLeads to adverse outcomes in other cohorts– May or may not help the “rule out” ACS May or may not help the “rule out” ACS

patientspatients More efficient options desiredMore efficient options desired

ED Specific StudiesED Specific Studies

Multiple small single arm studiesMultiple small single arm studies Hollander et al.Hollander et al.

– 500+ patient observational trial500+ patient observational trial ROMICAT 1ROMICAT 1

– 300+ patient observation trial300+ patient observation trial Small RCT’sSmall RCT’s

– Goldstein, GallagherGoldstein, Gallagher Larger RCT’sLarger RCT’s

– CT STAT, ACRIN 4005, ROMICAT 2CT STAT, ACRIN 4005, ROMICAT 2

ACRIN PA 4005 30-day OutcomesACRIN PA 4005 30-day Outcomes

Patients with negative CCTA can be safely Patients with negative CCTA can be safely discharged (0% event rate, 95%CI, 0.57)discharged (0% event rate, 95%CI, 0.57)

CCTA more efficientCCTA more efficient– Higher discharge rateHigher discharge rate– More rapid dischargeMore rapid discharge

More patients diagnosed with CAD (9 v 3%)More patients diagnosed with CAD (9 v 3%) Higher rate of positive cardiac catheterizationHigher rate of positive cardiac catheterization No increased rate of revascularizationNo increased rate of revascularization No difference in 30 day death or AMINo difference in 30 day death or AMI

ObjectivesObjectives

To compare health care utilization during 1 To compare health care utilization during 1 year post-randomizationyear post-randomization– Imaging, intervention, repeat ED visits, re-Imaging, intervention, repeat ED visits, re-

admissionadmission To compare major cardiac events during 1 To compare major cardiac events during 1

year post randomization for participants year post randomization for participants notnot found to have CAD during index visit found to have CAD during index visit

MethodsMethods

Study designStudy design– Randomized controlled trial (CCTA 2:1)Randomized controlled trial (CCTA 2:1)

SettingSetting– 5 sites5 sites

Patient EnrollmentPatient Enrollment– Not limited to times when testing availableNot limited to times when testing available– Mostly in EDMostly in ED– Could be in observation before testing decisionCould be in observation before testing decision

Methods: PatientsMethods: Patients

InclusionInclusion– > age 30> age 30– TIMI score 0-2TIMI score 0-2– No ischemia on ECGNo ischemia on ECG

ExclusionExclusion– Clearly noncardiac painClearly noncardiac pain– Comorbidity requiring admissionComorbidity requiring admission– Contraindications to CCTAContraindications to CCTA– Post randomizationPost randomization

• CrCl < 60 or PE protocol CT doneCrCl < 60 or PE protocol CT done

Methods: TestingMethods: Testing

CCTACCTA– Noncontrast calcium scoringNoncontrast calcium scoring– Contrast angiographyContrast angiography– B-blockers and NTG per local protocolB-blockers and NTG per local protocol– All readers ACC/AHA level 3All readers ACC/AHA level 3

• Local interpretations used clinicallyLocal interpretations used clinically

Stress testingStress testing– Imaging or not was a local decisionImaging or not was a local decision

Methods: Data CollectedMethods: Data Collected

Standardized Guideline Core CriteriaStandardized Guideline Core Criteria– HistoryHistory– Presence of chest pain at ED presentationPresence of chest pain at ED presentation– Associated symptomsAssociated symptoms– Initial ECGInitial ECG– TIMI risk scoreTIMI risk score– Cardiac markersCardiac markers

Methods: Follow-upMethods: Follow-up

Direct patient contactDirect patient contact Medical record reviewMedical record review

– Presenting institutionPresenting institution– Neighboring institutionNeighboring institution

Home visitsHome visits SSDISSDI

Methods: OutcomesMethods: Outcomes Resource utilization Resource utilization

– RevascularizationRevascularization– Cardiac testingCardiac testing– ED visitsED visits– Re-admissionRe-admission

One year outcomesOne year outcomes– DeathDeath

• Adjudicated for cardiac causeAdjudicated for cardiac cause

– Nonfatal AMI Nonfatal AMI • Adjudicated Adjudicated

Results: Patient CharacteristicsResults: Patient Characteristics

CCTA(n=907)

Traditional(n=461)

Age 49 +/- 8.9 50 +/- 9.5

Race (% white) 40% 35%

Female Gender 51% 56%

Hypertension 51% 50%

Hypercholesterolemia 27% 26%

Family History 30% 27%

Diabetes 14% 14%

Tobacco (current) 32% 34%

Cocaine (< week) 5% 4%

TIMI 0 or 1 87% 87%

One Year SafetyOne Year Safety

CCTA(n=907)

Traditional(n=461)

Difference (95% CI)

All-Cause Mortality 2 (0.2%) 3 (1%) -0.43% (-6.0, 5.2)

Cardiac Death 1 (0.1%) 0 0.1% (-5.5, 5.7)

AMI 11 (1%) 5 (1%) 0.1% (-5.6, 5.9)

Composite D/AMI 12 (1%) 5 (1%) 0.3% (-5.5, 6.0)

Revascularization 25 (3%) 7 (2%) 1.3% (-4.4, 7.0)

Enrollment through one yearEnrollment through one year

One Year Safety One Year Safety

CCTA(n=825)

Traditional(n=445)

Difference (95% CI)

All-Cause Mortality 2 (0.2%) 3 (0.7%) -0.43% (-6.2, 5.3)

Cardiac Death 1 (0.1%) 0 0.12% (-5.7, 5.9)

AMI 1 (0.1%) 1 (0.2%) -0.11% (-6.0, 5.8)

Composite D/AMI 2 (0.2%) 1 (0.2%) 0.02% (-5.9, 5.9)

Revascularization 0 2 (0.5%) -0.47% (-6.3, 5.4)

Patients Patients notnot found to have CAD found to have CAD

One Year Resource UseOne Year Resource Use

CCTA Traditional Difference (95% CI)

ED revisit 36% 38% -2.1% (-7.9, 3.7)

Admission 16% 17% -0.9% (-6.7, 4.9)

Cardiologist office 18% 13% 5.5% (-0.4, 11.3)

Testing & Meds

CCTA 0.2% 1% -0.9% (-6.8, 4.9)

Stress +/- imaging 9% 9% 0.9% (-4.9, 6.8)

Catheterization 3% 3% -0.2% (-6.0, 5.7)

Echocardiogram 6% 6% -0.2% (-6.0, 5.7)

Aspirin 34% 36% -3.2% (-8.9, 2.7)

Thienopyridines 4% 3% 1.7% (-4.2, 7.5)

Statins 24% 18% 5.6% (-0.2, 11.4)

After Hospital DischargeAfter Hospital Discharge

Stratified by CADStratified by CAD

CCTA - Trad - CCTA + Trad + CCTA ? Trad ?

# (%) 702/90777%

282/46161%

82/9079%

16/4613%

123/90714%

163/46135%

ED visit 32% 32% 41% 25% 37% 44%

Readmit 13% 11% 33% 31% 18% 23%

Cards visit

13% 6% 50% 56% 11% 16%

Aspirin 27% 31% 80% 81% 24% 36%

Statin 17% 16% 74% 56% 13% 15%

Antiplat 1% 2% 33% 25% 0% 1%

DiscussionDiscussion

Coronary CTA is accurate Coronary CTA is accurate – Compares well to cardiac catheterizationCompares well to cardiac catheterization

Normal or minimal disease on cathNormal or minimal disease on cath– Predicts freedom from events at 30 daysPredicts freedom from events at 30 days

A negative CCTA (<50% maximal A negative CCTA (<50% maximal stenosis) predicts freedom from events at stenosis) predicts freedom from events at one yearone year

Discussion Discussion

In the year following discharge there was In the year following discharge there was no increase in resource utilization no increase in resource utilization – Diagnostic testing for CADDiagnostic testing for CAD– EchocardiogramEchocardiogram– Medication useMedication use

But resources applied more appropriately But resources applied more appropriately since patients more likely to have since patients more likely to have determination of underlying diseasedetermination of underlying disease

LimitationsLimitations

Powered off primary aimPowered off primary aim– UL of 95% CI being less than one percent in UL of 95% CI being less than one percent in

patients with negative CCTApatients with negative CCTA Cannot exclude possibility that we did Cannot exclude possibility that we did

not detect small but real difference not detect small but real difference between groupsbetween groups

ConclusionsConclusions

A negative CCTA predicts low risk of 1 A negative CCTA predicts low risk of 1 year death, AMI or revascularizationyear death, AMI or revascularization

CCTA does not increase resource CCTA does not increase resource utilizationutilization

Shifts resources to where they are most Shifts resources to where they are most usefuluseful– More disease identified and treatedMore disease identified and treated– More patients without disease not treatedMore patients without disease not treated

AcknowledgementsAcknowledgements Hospital of the University of PennsylvaniaHospital of the University of Pennsylvania

– Site Investigators: Judd E. Hollander, MD Harold I. Litt, MD, PhDSite Investigators: Judd E. Hollander, MD Harold I. Litt, MD, PhD– Research Coordinators: Emily Barrows, Jeffrey Le, Shannon Marcoon, Research Coordinators: Emily Barrows, Jeffrey Le, Shannon Marcoon,

Julie Pitts, RN, Scott Steingall, RTJulie Pitts, RN, Scott Steingall, RT Penn State University Medical Center at HersheyPenn State University Medical Center at Hershey

– Site Investigators: James M. Leaming, MD, Harjit Singh, MD, Michelle Site Investigators: James M. Leaming, MD, Harjit Singh, MD, Michelle A. Fischer, MD, Steven Ettinger, MD, Carlos Jamis-Dow, MD, Kevin A. Fischer, MD, Steven Ettinger, MD, Carlos Jamis-Dow, MD, Kevin Moser, PhDMoser, PhD

– Research Coordinators: Swati Shah, Kevin Gardner, RN, Russell Research Coordinators: Swati Shah, Kevin Gardner, RN, Russell Dicristina, Susan OskorusDicristina, Susan Oskorus

Penn Presbyterian Medical CenterPenn Presbyterian Medical Center– Site Investigators: Laurence Gavin, MD, Anna Marie Chang, MDSite Investigators: Laurence Gavin, MD, Anna Marie Chang, MD– Research Coordinators: Christopher Decker, Michael Green, Katie Research Coordinators: Christopher Decker, Michael Green, Katie

O’Conor, Angela Roach, Kristy Walsh, Max WayneO’Conor, Angela Roach, Kristy Walsh, Max Wayne

AcknowledgementsAcknowledgements Wake Forest UniversityWake Forest University

– Site Investigators: J. Jeffrey Carr, MD, MSc, Daniel W. Entrikin, Site Investigators: J. Jeffrey Carr, MD, MSc, Daniel W. Entrikin, MD, Kim Askew, MD, James W. Hoekstra, MD, Simon Mahler, MD, MD, Kim Askew, MD, James W. Hoekstra, MD, Simon Mahler, MD, Chadwick D. Miller, MD, MSChadwick D. Miller, MD, MS

– Research Coordinators: Denise Boyles, Stephanie Bradshaw, Mark Research Coordinators: Denise Boyles, Stephanie Bradshaw, Mark Collin, Erin Harper, Lisa Hinshaw, MS, Jane Kilkenny, Megan Collin, Erin Harper, Lisa Hinshaw, MS, Jane Kilkenny, Megan Koonts, Lori Triplett, RNKoonts, Lori Triplett, RN

University of Pittsburgh Medical CenterUniversity of Pittsburgh Medical Center– Site Investigators: Charissa B. Pacella, MD, Joan M. Lacomis, MD Site Investigators: Charissa B. Pacella, MD, Joan M. Lacomis, MD

and Christopher R. Deible, MD, PhDand Christopher R. Deible, MD, PhD– Research Coordinators: Sara Vandruff, Barbara Early, Tina Vita, Research Coordinators: Sara Vandruff, Barbara Early, Tina Vita,

Dawn McBride Dawn McBride Brown University: Biostatistical/research designBrown University: Biostatistical/research design

– Constantine Gatsonis, PhD, Brad Snyder, MS, Sanaa Boudhar, MS, Constantine Gatsonis, PhD, Brad Snyder, MS, Sanaa Boudhar, MS, Patricia Fox, MS and Erin Greco, MSPatricia Fox, MS and Erin Greco, MS

AcknowledgementsAcknowledgements Data Safety Monitoring BoardData Safety Monitoring Board

– David Bluemke, MD, PhD (Chair), National Institute of Health; Todd David Bluemke, MD, PhD (Chair), National Institute of Health; Todd A. Alonzo, PhD, University of Southern California; Jon F. Merz, A. Alonzo, PhD, University of Southern California; Jon F. Merz, MBA, JD, PhD, University of Pennsylvania; Herbert Y. Kressel, MD, MBA, JD, PhD, University of Pennsylvania; Herbert Y. Kressel, MD, Beth Israel Deaconess Medical Center.Beth Israel Deaconess Medical Center.

Adjudication CommitteeAdjudication Committee– W. Frank Peacock, MD, Cleveland Clinic; Robert Hendel, MD, W. Frank Peacock, MD, Cleveland Clinic; Robert Hendel, MD,

University of Miami University of Miami Administration and Oversight – ACRIN PAAdministration and Oversight – ACRIN PA

– Cynthia Olson, Anthony Levering, Cynthia Price, Maria Oh, Patricia Cynthia Olson, Anthony Levering, Cynthia Price, Maria Oh, Patricia Blair, Martha Heckl, Charles Apgar, Mary Kelly, Mitchell Schnall Blair, Martha Heckl, Charles Apgar, Mary Kelly, Mitchell Schnall MD, PhDMD, PhD