Overview. Health and economic burden of coronary artery disease (CAD) Pitfalls in care of patients suspected of having CAD

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1 Quality Challenges and Pitfalls in the Evaluation of Patients with Suspected Heart Disease Joseph A. Ladapo, MD, PhD Assistant Professor of Medicine Department of Population Health NYU School of Medicine Disclosures: K23 HL Award from National Heart, Lung, and Blood Institute; Consultant for CardioDx, Inc Overview Health and economic burden of coronary artery disease (CAD) Pitfalls in care of patients suspected of having CAD Approaches to improve quality of care Introduction to Corus CAD, a gene expression test for CAD 2 1

2 Coronary Artery Disease (CAD) is a Major Public Health Challenge Epidemiology 15.4 million adults in the US live with CAD 6.4% of adults overall; 7.9% of men and 5.1% of women Mortality Accounts for over 386,000 deaths annually (1 in 6 of all deaths) More than half of sudden cardiac deaths occur in people with no prior history of heart disease Myocardial infarction Nearly one million new or recurrent heart attacks each year Early diagnosis is important because treatment & preventive practices significantly reduce morbidity and mortality National Health Interview Survey, 2010; Go, Circulation Healthcare Utilization and Costs Attributable to CAD are Substantial Healthcare utilization and costs CAD costs $195.2 billion in direct and indirect costs annually (2009) In 2006, Medicare spent $11.7 billion on inpatient care for CAD By 2030, medical costs for CAD (real 2010$) projected to increase 100% Ambulatory care In 2009, there were over 14 million ambulatory care visits with CAD as the first-listed diagnosis Hospital care 1.3 million hospital admissions with CAD listed as the first diagnosis 954,000 percutaneous coronary interventions (PCIs), 397,000 cardiac bypass surgeries, 1.03 million diagnostic cardiac catheterizations National Health Interview Survey, 2010; Go, Circulation

3 Cardiac Stress Testing Source of picture: American College of Cardiology, CardioSmart website Primary Care Physicians Routinely Manage Patients With Suspected or Diagnosed CAD ~4M Stable, Symptomatic Patients Suggestive of Coronary Disease Annually Diagnostic Tools Primary Care Clinical Factors EKG Treadmill Cardiology Often Repeat Testing Stress Echo Nuclear Imaging CT Angiography Invasive Angiography Obstructive CAD is not found in ~60% patients 1 ~$4.5B annual expenditures 2 1 Patel et al, N Engl J Med 2010;362:886-95; COMPASS study. 2 IMV Market Reports 6 3

4 Ambulatory Care: Cardiac Stress Tests In Patients Without CAD, From 1993 To ,000,000 4,000,000 No. of Tests 3,000,000 2,000,000 1,000,000 - Any cardiac stress test Stress imaging Avg. annual cost in All cardiac stress tests Avg. annual cost in $820M $2.0B Stress imaging $550M $1.9B Source: Ladapo et al, Annals of Internal Medicine Opportunities For Quality Improvement Presentation Title Goes Here 8 4

5 Despite Wide Array of Available Tests for Working Up CAD, Patients Routinely Encounter 1. Diagnostic uncertainty 2. Unnecessary testing and procedures 3. Unnecessary radiation exposure 9 Challenges to Clinical Care: Diagnostic Uncertainty Presentation Title Goes Here 10 5

6 Uncertainty About How to Interpret Diagnostic Test Results is Common Bayes theorem defines how pretest disease risk and diagnostic test performance can be used to guide interpretation of test results Missed or misdiagnosed Correctly identified Reverend Thomas Bayes 11 Stress Test Effectiveness in Diagnosing CAD: Results From Meta-analyses Stress MPI Sens Spec # studies Stress ECHO Sens Spec # studies Garber et al Fleischma nn et al Mowatt et al* Mowatt et al** 88% 77% 10 87% 64% 27 76% 65% 10 92% 74% 4 76% 88% 6 85% 77% *includes or **excludes patients with prior myocardial infarction Garber, Annals 1999; Fleischmann, JAMA 1998; Mowatt, HTA

7 Physicians Interpret Test Results in a Bayesian Manner Stress MPI example Most frequently performed imaging stress test Sensitivity = 87%, Specificity = 64% Normal test result With a pretest probability of 20%, post-test probability of CAD is 5% after a normal test result With a pretest probability of 60%, post-test probability of CAD is 23% after a normal test result Abnormal test result With a pretest probability of 20%, post-test probability of CAD is 38% after an abnormal test result With a pretest probability of 60%, post-test probability of CAD is 78% after an abnormal test result 13 Referral Bias also Influences Diagnostic Accuracy and Test Interpretation Referral bias Sometimes called verification bias or workup bias Occurs because higher-risk patients are preferentially referred to cardiac catheterization Bayesian methods needed to adjust diagnostic test performance for referral Biases clinical decision-making Because it biases test performance, it may also bias clinical decision-making Most studies do not account for referral Studies of stress test performance do not adjust for this phenomenon so estimates of sensitivity and specificity biased Begg, Biometrics

8 Presentation Title Goes Here Ladapo et al, JAHA Cardiac Catheterization Referral Rates After Normal Exercise ECHO or MPI Results Referral rates are low after a normal study Range of ~1% to 5% generally Homogenous Geographic location and patient characteristics vary but little variation in referral rates Ladapo et al, JAHA

9 Cardiac Catheterization Referral Rates After Abnormal Exercise ECHO or MPI Results Referral rates higher after an abnormal test Range of ~20% to 50% generally Heterogeneity Significant variation in referral rates Ladapo et al, JAHA Observed vs. True Diagnostic Performance of Exercise ECHO 100% 80% 91% 81% 99% 60% 40% 40% 20% 0% Sensitivity Observed performance Specificity True performance True performance = observed performance after adjustment for referral 18 9

10 Observed vs. True Diagnostic Performance of Exercise MPI 100% 91% 97% 80% 60% 40% 44% 67% 20% 0% Sensitivity Observed performance Specificity True performance True performance = observed performance after adjustment for referral 19 Challenges to Clinical Care: Unnecessary Testing and Procedures Presentation Title Goes Here 20 10

11 Unnecessary Testing is Common Our Threshold for Testing Patients is Falling 39,515 patients undergoing stress MPI between at Cedars Sinai Incidence of abnormal scans fell from 41% 9% Incidence of ischemic scans fell from 30% 5% Only 3% of patients who did not have typical angina and could exercise had an abnormal scan Rozanski, JACC Unnecessary Procedures are Common Cardiac Catheterization Frequently Performed Needlessly 398,978 patients in American College of Cardiology (ACC) National Cardiovascular Data Registry (NCDR) Noninvasive cardiac testing performed in 84% of patients prior to catheterization Only 1 in 3 patients were found to have obstructive coronary disease No coronary artery disease was reported in 39% of patients Patel, NEJM

12 Inappropriate Imaging is Common What is appropriate imaging? Imaging that provides (1) accurate information, (2) influences behavior, and (3) yields benefits that outweigh risks In general, imaging in intermediate to high-risk patients is appropriate (diabetics, AAA, PVD, angina/ischemic equiv., ECG uninterpretable) Number of inappropriate cardiac imaging stress tests in patients evaluated for CAD has risen Primary care doctors fare worse than cardiologists Presented at American College of Cardiology 63rd Annual Scientific Session, March 2014 in Washington, DC 23 Challenges to Clinical Care: Unnecessary Radiation Presentation Title Goes Here 24 12

13 25 Unnecessary Radiation Exposure is a Growing Problem Potential harms related to radiation exposure are poorly understood Stress MPI accounts for 22% of cumulative effective radiation from medical sources One MPI 1,000 chest x-rays msv Persons at risk for repeated radiation exposure, such as healthcare workers and the nuclear industry, typically restricted to max 100 msv every 5 years Columbia University Medical Center 1,097 consecutive patients, 8-10 years of follow-up Multiple MPIs performed in 424 patients (39%) Median cumulative effective dose from MPI was 29 msv Median cumulative effective dose from medical sources was 64 msv Medicare population Between , 34% of enrollees underwent repeat testing US nonelderly population 952,420 adults in 5 US markets ( ) Among patients undergoing cardiac imaging, mean cumulative dose 16.4 msv ( msv) MPI accounted for 74% of cumulative dose Fazel, NEJM 2009; Einstein, JAMA 2010; Gerber, Circulation 2009; Lucas, Circulation 2006; Chen, JACC

14 Improving Quality Of Care Presentation Title Goes Here 27 Improving Quality of Care: Reducing Unnecessary Testing Appropriate use criteria Growing physician awareness of appropriate use criteria for diagnostic testing in patients suspected of having CAD ACC and United Healthcare registry reported that 34% of stress MPIs were inappropriate or of uncertain appropriateness Insurer policies and regulation Prior authorization by radiology benefits managers Reductions in reimbursement Medicare released national coverage decision requesting more evidence for coronary CT angiography (CTCA) Patient/Professional education Informed decision-making Shared decision-making Professional society scrutiny Impact on health is unknown and needs to be studied Shaw, JACC: CV Imaging 2010; Gibbons, JACC

15 Improving Quality of Care: Comparative Effectiveness Research Comparative effectiveness research (CER) Because tests vary in diagnostic accuracy, initial test choices may influence outcomes, independent of regional/physician care patterns and patients risk factors Large data set analyses and clinical trials Stress MPI vs. ECHO (unpublished data) 11,794 patients underwent stress testing and were followed for 12 months Mean age 53 yrs, 62% male Risk of major adverse cardiovascular events lower after stress ECHO (aor 0.6, p<0.001) compared to MPI Stress MPI vs. ECHO vs. CTCA 282,830 Medicare patients undergoing stress testing and followed for 6 months Mean age 74 yrs, 46% men Risk of acute MI lower after stress ECHO (aor 0.8, p<0.03) and CTCA (aor 0.6, p<0.04) compared to MPI Ladapo et al, in development; Shreibati, JAMA Improving Quality of Care: Clinical Decision Analysis Clinical decision analysis Integrates mathematical modeling, uncertainty, and patient preferences to identify optimal care strategies Informs health policy and clinical practice Patient preferences Impact of false positive tests Preferences over medical management vs. invasive management of CAD Radiation concerns No models of patient care have integrated (1) patients preferences about false positives and (2) accurate measures of diagnostic accuracy (referral-adjusted) Ladapo et al, JACC

16 Improving Quality of Care: Optimizing Diagnostic Accuracy Research on diagnostic accuracy of stress testing that accounts for referral patterns to cardiac catheterization is needed Wider dissemination of accurate information about diagnostic performance Coronary CT angiography High-resolution visualization of coronary anatomy Blood-based gene-expression test for diagnosing obstructive CAD (Corus CAD) Limitation: Ischemic heart disease occurs in absence of coronary stenosis 31 Gene expression score (GES) Measures Expression of 23 Genes From Peripheral Blood Cells 32 16

17 Blood-Based Genomic Test: A New Diagnostic Test to Rule-out CAD Gene expression score (GES) First clinically validated gene expression test for assessing obstructive CAD (>50% stenosis in a major coronary artery) Algorithm based on the peripheral blood gene expression of 23 genes, gender and age Molecular basis includes genes and pathways with known involvement in atherosclerosis and its progression GES quantifies risk of CAD Targeted application as a first line, rule-out test, prior to additional stress testing or cardiac catheterization Stress testing often perceived as gatekeeper to cardiac catheterization GES may be gatekeeper to stress testing Nondiabetic patients only 33 COMPASS Trial Overview Purpose Independent validation of Corus CAD in stable symptomatic patients referred for MPI (intended use population) Also evaluated MPI performance in the real-world clinical setting Study Design Prospective, multi-center, blinded study 19 U.S. sites, 431 patients QCA Core Lab: Cardiovascular Research Foundation, NY CTA Core Lab Readers: Szilard Voros, MD, James Adams, MD MPI Core Lab Reader: Timothy M Bateman, MD Steering committee: Greg Thomas, MD, MPH, John McPherson, MD, Alexandra Lansky, MD, Szilard Voros, MD Patient Inclusion/Exclusion Symptomatic (chest pain or anginal equivalent) who have been referred for MPI for the workup of suspected obstructive CAD Non-diabetic No known obstructive CAD, prior myocardial infarction, or prior revascularization procedure Thomas, Circ Genetics

18 COMPASS Trial Design COMPASS (Coronary Obstruction Detection by Molecular Personalized Gene Expression) Primary Endpoint: GES performance by ROC analysis Steering Committee: Greg Thomas, MD, MPH, John McPherson, MD, Alexandra Lansky, MD, Szilard Voros, MD 19 U.S. sites, 431 patients Specificity 36 18

19 GES Performance in Independent Validation Studies GES Performance* COMPASS (N=431)** PREDICT (N=526) Sensitivity 89% 85% NPV 96% 83% Specificity 52% 43% Prevalence 15% 37% *Performance associated with a score threshold of 15 **ROC curve area (AUC) for GES was 0.79 compared to site/core-lab AUCs for MPI were 0.59 and IMPACT-Cardiology & -Primary Care Providers Trial Designs IMPACT-CARD Patients Referred from Primary Care N=83 IMPACT-PCP Patients Presenting with Angina Related Symptoms N=251 Cardiology Primary Care GES Initial Decision: Medical Management Non-Invasive Test Cardiac Cath GES-driven Decision: Medical Management Non-Invasive Test Cardiac Cath Primary Analysis: Change in diagnostic test utilization with vs without GES Secondary Analysis: Change in testing vs. historical controls Herman L et al. JABFM 2014;27(2): McPherson JA et al. Crit Pathw Cardiol 2013;12(2):

20 Clinical Utility of GES in Evaluation of Patients with Suspected CAD IMPACT-Cardiology (n=83): 63% of patients had GES 15 (52/83) and 37% of patients had scores > 15 (31/83) 58% of patients saw a change in diagnostic testing* following GES (p<0.001) IMPACT-PCP (n=251): 51% of patients had GES 15 (127/251) and 49% of patients had scores > 15 (124/251) 58% of patients saw a change in diagnostic testing* following GES (p<0.001) Percentage of Patients with Decreased Testing Percentage of Patients with No Change in Testing Percentage of Patients with Increased Testing Cardiology PCP GES 15 56% 44% 0% 29/52 GES >15 10% 39% 52% 3/31 GES 15 60% 38% 2% 76/127 48/127 3/127 GES >15 14% 47% 39% 23/52 12/31 0/52 16/31 17/124 58/124 49/124 * E.g., myocardial perfusion imaging, CT Angiography (CTA) and/or invasive angiography Herman L et al. JABFM 2014;27(2): McPherson JA et al. Crit Pathw Cardiol 2013;12(2): Conclusions Despite the high prevalence and substantial economic burden of CAD, significant challenges to effectively diagnosing and treating patients exist Major quality issues include diagnostic inaccuracy, unnecessary testing and procedures, and radiation exposure Opportunities exist to improve care through multiple health policy, research, and patient-oriented dimensions A gene expression test for CAD, has promising diagnostic characteristics and may play a role in improving care and reducing unnecessary testing 40 20

21 Thank you! Presentation Title Goes Here 41 21