Gender Bias in Cardiovascular Disease

Report
One Year Outcomes and Resource
Utilization in ACRIN PA 4005:
Multicenter RCT of Rapid Rule-Out Strategy of
CCTA vs Traditional Care
Department of Emergency Medicine
University of Pennsylvania Health System
Judd E. Hollander, MD
Professor
Clinical Research Director
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
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
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
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
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
Objectives

To compare health care utilization during 1
year post-randomization
– Imaging, intervention, repeat ED visits, readmission

To compare major cardiac events during 1
year post randomization for participants
not found to have CAD during index visit
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
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
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
Methods: Data Collected

Standardized Guideline Core Criteria
–
–
–
–
–
–
History
Presence of chest pain at ED presentation
Associated symptoms
Initial ECG
TIMI risk score
Cardiac markers
Methods: Follow-up


Direct patient contact
Medical record review
– Presenting institution
– Neighboring institution


Home visits
SSDI
Methods: Outcomes

Resource utilization
–
–
–
–

Revascularization
Cardiac testing
ED visits
Re-admission
One year outcomes
– Death
• Adjudicated for cardiac cause
– Nonfatal AMI
• Adjudicated
Results: Patient Characteristics
CCTA
(n=907)
Traditional
(n=461)
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%
Age
One Year Safety

Enrollment through one year
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)
One Year Safety

Patients not found to have CAD
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)
One Year Resource Use

After Hospital Discharge
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%
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)
5.5% (-0.4, 11.3)
Testing & Meds
CCTA
Stratified by CAD
CCTA -
Trad -
CCTA +
Trad +
CCTA ?
Trad ?
702/907
77%
282/461
61%
82/907
9%
16/461
3%
123/907
14%
163/461
35%
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%
# (%)
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
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
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
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
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
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, Sanaa Boudhar, MS,
Patricia Fox, MS and Erin Greco, MS
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

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