Use of Coronary Artery Calcium Scoring for Risk Stratification

Transcription

1 Use of Coronary Artery Calcium Scoring for Risk Stratification Leslee J. Shaw, PhD, MASNC, FACC, FAHA, FSCCT Professor of Medicine Co-Director, Emory Clinical CV Research Institute Director, Women s Health Research Emory University School of Medicine Atlanta, Georgia leslee.shaw@emory.edu Disclosures: Dean s Distinguished Faculty Award Emory University; Albert E. Levy Scientific Research Award; Woodruff Foundation; Antinori Foundation: NIH-NHLBINHLBI (1U01HL ), Past-PresidentPresident American Society of Nuclear Cardiology, Vice-President: SCCT, AHRQ Study Section Health Economics & Outcomes Research. Cardiovascular Risk Detection in Women Women are at High Risk of Dying from CVD Global Risk Scores Perform Poorly in Women Coronary Artery Calcium is Prevalent In Women CAC Scanning is a Low Cost, Safe Procedure with Tremendous Evidence as to Risk Detection 1

2 Detecting Subclinical Atherosclerosis Leading to Improved Population Health CV Disease is Leading Cause of Death Worldwide Recent Declines Yet Substantial Detection Gap Remains Early Intervention Model By Detecting Early (i.e., sublinical) Atherosclerosis, Preventive Care Results in Premature Morbidity & Mortality - End-Stage, Costly Care (e.g., Heart Failure) Source: statistics) Screening for Population Health & Healthcare System Innovation Healthcare System Should be Transformed to Strive for 3 Goals (i.e., Triple Aim ) Improving Health for Populations by Attacking Causes of Ill Health Improving Health Care for Individuals Along 6 Dimensions (Safety, Effectiveness, Patient- Centeredness, Timeliness, Efficiency, & Equity) Reducing, or at Least Controlling, Cost of Care Source: Fleming C. Berwick brings the Triple Aim to CMS. Health Affairs Blog Sep 14. ( berwick-brings-the-triple-aim-to-cms/). 2

3 Current Economic Burden of Cardiovascular Care Spending / Revenues - % of GDP CV Care Costs = ~43 of Each Medicare $ Current CV Screening - Lipid Panel ~60-80% of US Adults Are At-Risk Current Reimbursement is a Zero-Sum Game Mathematically, Each Gain (or Loss) is Balanced by Losses (or Gains).with exception Compelling Quality Evidence Supporting Improved Clinical Outcomes +/- Efficiency of Care 3

4 Essential Framework To Meet Strict Requirements of Quality Research 3) Value: Is it worth it? 1) Efficacy: Can it work? 2) Effectiveness: Does it work? Application of Quality Standards to Screening for Subclinical Atherosclerosis 1) Efficacy: Can it work? Identify the Vulnerable Individual at-risk for Acute Coronary Event 2) Effectiveness: Does it work? Comparative Effectiveness Research Is there relevant trial evidence? Risk Methodologies - Well Developed but Screening Tools Have Varied Evidence Base 3) Value: Is it worth it? Can We Afford to Screen the Adult Population? 4

5 Cardiovascular Risk Detection in Women General Approaches to Risk Stratification 10 Yr. CHD Death or MI Risk Framingham Offspring & Cohort Women & Men Percent Women Men Age (years) Source: Pasternak RC, Abrams J, Greenland P, Smaha LA, Wilson PW, Houston-Miller N, Smaha L. Bethesda Conference #34: Identification of CHD and CHD risk: Is there a detection gap? JACC 2003 Jun 4;41(11):

6 Who to Screen? Low Risk Framingham Risk Score 6-9.9% X No Testing Intermediate Risk Framingham Risk Score % CVD Screen High Risk Framingham Risk Score 20% Rx 2 0 Prevention Goals Framingham Risk Score (FRS) Limitations FRS Basis for CVD Screening and Rx to 2 0 Prevention Goals FRS underestimates CVD in men <60 & women <70! Notably Family Hx CHD, Metabolic Syndrome Michos (2006) Cross-Sectional Study of 2,447 Asymptomatic, non-dm Women Majority (84%) of Women w/ Significant CAC ( 75th %ile) were Classified as Low-Risk by FRS Source: Michos Atherosclerosis 2006;184(1):201-6., 6., Nasir JACC 2005 Nov 15;46(10):

7 Cumulative All-Cause Mortality - Framingham Risk Score 6-9.9% Cumulative Mortality Incidence (%) Women (n=1,072) Men (n=1,291) ~56 years old ~46 years old Follow-up Duration (in years) Framingham Risk Score-Adjusted Hazard Ratio: 1.44 ( ), p=0.022 Cardiovascular Risk Identification 2011 Effectiveness-Based Guidelines for Prevention of CVD in Women 2013 ACC/AHA Guidelines - Assessment of Cardiovascular Risk 2014 AHA Stroke Prevention Guidelines in Women 7

8 Risk Scores - Basis for Preventive Care New Risk Calculator Black, Source: Goff J Am Coll Cardiol 2014;63: ,. Kavousi,JAMA 2014;311: , Stone J Am Coll Cardiol 2014;63: We Can Improve Preventive Screening! Black, New Risk Calculator External Validation Model Statistics Discriminating Low to High Risk Subsets Unimpressive Risk Overestimation African-AmericanAmerican Limitations of Risk Scores for Women, Racial / Ethinic Minority Cohorts Potential for Imaging to Improve Risk Detection Source: Muntner JAMA 2014;311: , Cook JAMA Int Med 2014;174: , Ridker Lancet 2013;382:

9 We Can Improve Preventive Screening! Black, New Risk Calculator External Validation Model Statistics Discriminating Low to High Risk Subsets Unimpressive Risk Overestimation African-AmericanAmerican Limitations of Risk Scores for Women, Racial / Ethinic Minority Cohorts Potential for Imaging to Improve Risk Detection Source: Muntner JAMA 2014;311: , Cook JAMA Int Med 2014;174: , Ridker Lancet 2013;382: NIH-NHLBI NHLBI Working Group - Identification of High-Risk or Vulnerable Patients Atherosclerotic Plaque Prone to Acute Events - Termed Vulnerable or High-Risk Search for Vulnerability Prior to Symptom Onset Has Been Elusive Source: Fleg J Am Coll Cardiol CV Img 2012;5: , Motoyama J Am Coll Cardiol

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11 Coronary Artery Calcium (CAC) & Atherosclerotic Disease Development Coronary Artery Calcium A Subcomponent of Atheroma Subclinical Atherosclerosis Source: Bostrom J Clin Invest 1993;91: , Hirota Am J Pathol 1993;143: , Shanahan J Clin Invest 1994;93: , O Rourke Circulation 2000;102: , Nasir Am Heart J 2003;146: , 11

12 CT Detection of Calcified Plaque Technical Reasons: Non-Contrast CT Safe, Low Dose Exposure (~1 msv) Low Cost ($69-$99) Easy to Measure: Agatston Score = Area (A) x Plaque Density (D) in Hounsfield Units (HU) Clinical Reasons: Accurate Across Manufacturers Prevalence w/ Age & Risk Scores Target Screening in Middle Age - Elderly Strong Relationship to Outcome Source: Okwuosa J Am Coll Cardiol 2011;57: Prevalence (%) of CAC in 12,936 Asymptomatic Men & Women < Women Men >70 Source: Nasir Am J Cardiol 2004;93:

13 Normal Coronaries with No Coronary Artery Calcium Coronaries with Small Amount of Coronary Artery Calcium Coronaries with Extensive Coronary Artery Calcium PROGNOSIS & RISK RECLASSIFICATION Coronary Artery Calcium Score Scale Linear Scale of Progressively Higher Event Rates 0 None Low Risk Mild Risk Moderate Risk High Risk 1,000 Very High Risk Articles ( ): 2015): Women vs. Men Race / Ethnicity Diverse Ages Smokers Symptomatics Diabetics Hypertension Metabolic Syndrome 100s peer-reviewed manuscripts : 99.4% Clinical Patient Series on Long-Term Survival First Prognostic Series (N=10,377) Time to Follow-up (Years) : 97.8% : 95.2% : 90.4% 1,000: 81.8% Source: Shaw Radiology 2003;228:

14 NIH-NHLBI NHLBI Multiethnic Study of Atherosclerosis (MESA) Coronary Artery Calcium as Predictor of CV Events in 4 Ethnic Population Cohorts 6,814 Asymptomatic People Ages years Source: Detrano NEJM 2008;358: Event Rates by CAC Scores Event Rate at 5 Yrs [%] All Subjects Men Women 73% 17% 10% 59% 24% 17% 85% 11% 5% p< p< p< p= p= p=0.002 p=0.02 p=0.48 p= < < < CAC Categories Data = Event Rates (95%CI) Source: Erbel JACC 2010;56:

15 Risk-Adjusted Survival by CAC Across Age Deciles in Women & Men Cumulative Risk-Adjusted Survival Source: Raggi J Am Coll Cardiol 2008 Jul 1;52(1): Long-Term Survival by CAC in 9,715 Screened Patients Ages years (n=936 deaths) 0.6 Model Χ 2 =588, p< Cumulative All-Cause Mortality CAC 1,000 (p<0.0001) CAC (p<0.0001) CAC (p<0.0001) CAC (p<0.0001) CAC 1-10 (p<0.0001) CAC Follow-up (in years) Source: Shaw Annals of Internal Med

16 NIH-NHLBI NHLBI MESA: Predictive Value of CAC In Women Low Framingham Risk (FRS) Women w/ CAC Score >0 had 6- Fold Increased Risk for CHD & CVD Events vs. Women w/o CAC Low FRS Women,, Advanced CAC (i.e., Score 300) - Highly Predictive of CVD Events in Women CAC Score % / yr. Absolute CVD Risk = Risk Equivalent Status Source: Lakoski Arch Int Med 2007;167(22): Year All-Cause Mortality in Women & Men with Low-Intermediate Framingham Risk Score by CAC Strata Women (n=1,072) Men (n=1,291) Cumulative Mortality Incidence (%) CAC 400 CAC CAC CAC 1-10 CAC 0 CAC 400 CAC CAC CAC 1-10 CAC 0 p<0.001 Source: Kelkar (under review) Follow-up Duration (in years) 16

17 Hazard Ratio for All-Cause Mortality in Women vs. Men by CAC Scores from 0 to 400 & Ages <55 and 55 years Hazard Ratio (95% CI) Age <55 Years (n=1,771) Non-Smokers (n=767. p=0.92) Smokers (n=430< p<0.001) p=0.21 p=0.84 Source: Kelkar (under review) p=0.55 p< Age 55 Years (n=592) p<0.001 p=0.59 p=0.002 Coronary Artery Calcium Score Subsets p<0.001 p< CAC & Improved Adherence to Preventive Therapy / Lifestyle s Behavioral modification Weight Loss More Effective Higher CAC Scores (p<0.001) Prospective Army Coronary Calcium Trial 15 studies = 3 RCT & 12 observational studies Although no standardized approach used, CAC screening enhanced medication adherence in 13 of 15 studies Source: Kalia Atherosclerosis 2006;185:394-9., MamuduAtherosclerosis 2014;236: , Miedema Circ Cardiovasc Qual Outcomes 2014;7:

18 CAC - Improved Adherence Prevention Adherence is Suboptimal ~5% of Adults - Physically Active ~43% of Adults with CVD on Statins ~57% of Adults - Cholesterol Tested in 5 yrs... Direct Cost of Poor Adherence $ b Annually Up to 80% of CVD could be prevented by eliminating obesity, unhealthy diets & physical inactivity Source: Ockene Circulation 2011;124: ; Ho Circulation 2009;19: NIH-NHLBI NHLBI Multi-Ethnic Study of Atherosclerosis (MESA): Therapeutic Risk Benefit with Coronary Calcium 950 subjects from MESA who met criteria for JUPITER trial (20 mg rosuvastatin) Number Needed to Treat Source: Blaha Lancet 2011;378: CAC Scoring 18

19 MESA: Net Reclassification Improvement For Estimating Cardiac Events Comparative Effectiveness of Various Screening Modalities NRI = Compare Risk Score Model 1 vs. + New Marker Model 2 % Newly Detected Low Risk % Newly Detected High Risk % (±) New Low + High Risk = NRI Source: Pencina Clin Chem Lab Med 2010;48: MESA: Net Reclassification Improvement (NRI) For Estimating Cardiac Events Comparative Effectiveness of Brachial Flow Mediated Dilation (FMD), Ankle Brachial Index (ABI), High Sensitivity C-Reactive Protein (Hs-CRP), Carotid Intima-Media Thickness (C-IMT) vs. Coronary Artery Calcium (CAC) NRI: FRS Model vs. FRS + Screening Test Prognostic Models Model #1 Model #2 Model #3 Model #4 Comparative NRIs: NRI FRS + Brachial Flow Mediated Dilation 2.4% FRS + Ankle Brachial Index 3.6% FRS + High Sensitivity CRP 7.9% FRS + Family History 16.0% Model #5 FRS + Carotid Intima-Media Thickness 10.2% Model #6 FRS + Coronary Artery Calcium 65.9% Models estimating 7-y MI, CHD death, cardiac arrest, or angina followed by coronary revascularization FRS: Framingham Risk Score MESA: Intermediate Risk (n=1,330) Source: Polonsky JAMA 2010;303: , Yeboah JAMA 2012;308:

20 Importance of Examining All-Cause Mortality When assessing biomarkers, supportive arguments for use of all-cause mortality as a composite measure: Complementary Evidence from Disease-Specific Models Long-term Mortality Data = Closer to Life Expectancy Potential Harm Induced Following Screening Non-Cardiac Procedural / Treatment Complications Hospital-Acquired Infection Poor Compliance to Preventive Therapies e.g., Diabetes Source: Black J Natl Cancer Inst 2002;94: ; Steele BMJ 2011;343:d6397 COronary CTA The CONFIRM Registry: CTA EvaluatioN For Clinical Outcomes: An InteRnationalnational Multicenter Registry v.1. CONFIRM, v.2. CONFIRM, expected Dynamic Registry = ~50,000 Consecutive Patients Undergoing CT Derivation Cohort: 12 sites - 6 countries (US, Canada, Germany, Switzerland, Italy, S. Korea) Validation Cohort: 6 sites (Miami, California, Vancouver, New York, Innsbruck, Seoul) New Sites: 3 sites (Milan, Italy; Lisbon, Portugal; Warsaw, Poland) ~12-14K14K Source: Min JCCT 2011 Mar-Apr;5(2):

21 Application of Quality Standards to Screening for Subclinical Atherosclerosis Efficacy Risk Detection based on Acute CV Event or Chronic Dz Model Effectiveness Research Comparative Effectiveness Research Is there relevant trial evidence? Risk Methodologies are Well Developed but Screening Tools Have Varied Evidence Base Cost Implications Can We Afford to Screen the Adult Population? Economics of Screening for Cardiovascular Disease Upfront Costs Improved Detection of Risk Beyond Established, Traditional Risk Markers at a Low, Upfront Cost <$100 Downstream or Induced Costs Consider Not Only Upfront Costs but Induced Costs Can be Upwards of 100-fold Greater Incurring Lifetime Costs of Care Judging the Economic Impact of Screening Requires Accounting of Upfront + Induced Costs Source: Shaw Can J Cardiol 2013;29:350-7., Mark DB, Shaw LJ, Lauer MS, O Malley P, Heidenreich P. 34th Bethesda Conference: Task force #5 Is atherosclerotic imaging cost effective? J Am Coll Cardiol 2003;41: , 21

22 Upfront Screening Costs What is Added Cost of CV Imaging to the Screening Examination? NIH-NHLBI NHLBI MESA: Cost* of Index Screening (N=6,814) Newly Detected Risk Factors n= 1,741 (25.5%) Cost (/1,000 Screened) $120,641 Newly Detected High Risk n= High Risk Findings Hs-CRP ABI C-IMT CAC 1,759 (25.8%) 153 (2.2%) 873 (12.8%) 485 (7.1%) p value < < Added Cost (/1,000 Screened) $6,512 $156,448 $75,195 $60,617 *All costs are based on Medicare reimbursement rates and inflation-corrected US BLS + discounted Abbreviations: ABI: Ankle Brachial Index, Hs-CRP: High Sensitivity C-Reactive Protein, C-IMT: Carotid Intima-Media Thickness, CAC: Coronary Artery Calcium 22

23 Induced Costs Does CV Imaging Induce Excess Costs Following Screening? Do Costs Represent Pseudo- Disease or Clinical Need? Particular Focus on Near-Term Increases in Cost Attributable to Prior Testing Testing Begets Testing! Don t Open the Flood Gate! Inappropriate Follow-up Testing Apparently Well, Asymptomatic Population Negatives - Screening Test American College of Cardiology Inappropriate Indication Positives ABIM Initiative to Curb Overuse in Medicine - Top 5 List - Reduce Testing of Asymptomatics Induce Unwarranted Test Utilization + 1 or more Diagnostic Tests + Invasive Testing + Serial / Annual Testing 23

24 Cumulative CV Procedural $ NIH-NHLBI NHLBI MESA Registry: CV Procedural Spending* Among Asymptomatic Individuals with Low & High Risk Hs-CRP High Risk Hs-CRP Did Not Induce Near-term Costs $10,000 $8,000 $6,000 $4,000 $2,000 $0 Year 1-3 p=ns Hs-CRP >3 mg/dl Hs-CRP 3 mg/dl Follow-up Time (in Years) *Medicare reimbursement rates Cumulative CV Procedural $ $10,000 NIH-NHLBI NHLBI MESA Registry: CV Procedural Spending* Among Asymptomatic Individuals with Low to High Risk CAC Scores $8,000 $6,000 $4,000 $2,000 $0 *Years 1-10: p<0.001 CAC 400 CAC CAC < Follow-up Time (in Years) Prompt Testing Patterns High rates of: Stress Testing Diagnostic Echocardiograms X-rays MRI Invasive Angiography PCI / CABS *Medicare reimbursement rates CAC Screening Testing Begets Testing High Costs of Care 24

25 Cumulative CV Procedural $ NIH-NHLBI NHLBI MESA Registry: CV Procedural & Medication Spending* Among Asymptomatic Individuals with Low to High Risk CAC Scores $10,000 $8,000 $6,000 $4,000 $2,000 $0 Procedural Costs *Years 1-10: p<0.001 *Medicare reimbursement rates CAC 400 CAC CAC < Follow-up Time (in Years) Cumulative CV Medication $ $30,000 $25,000 $20,000 $15,000 $10,000 $5,000 CAC Screening High Costs of Care $0 Medication Costs *Years 1-10: p<0.001 CAC 400 CAC Follow-up Time (in Years) CAC <100 NHLBI MESA: Rates of New Onset Angina* for Low to High Risk CAC Scores CAC 400 CAC <400 84% of Procedures Performed Following New Onset Angina Rarely Inappropriate Indications for Angiography or Coronary Revascularization *All angina rates adjudicated by an independent panel with demonstrable evidence of angiographic CAD or ischemia. 25

26 Interpreting the NHLBI MESA Cost Findings Testing Begets Testing Was Confirmed in MESA! Induced, High Costs of Care Support the Lack of Payer Coverage Policies for CAC Screening Importantly, High Risk CAC is a Harbinger of the Transition from Quiescent, Subclinical Atherosclerosis to Symptomatic Ischemic Heart Disease Underlying Rationale for High Resource Consumption Patterns Not Screen-Detected Pseudo-Disease Conclusions Women Continue To Be At High Risk for CVD!!! Integration of Risk Factors into A Global Risk Score Underestimates Risk in Women Greatest Point Value is Age!!! Levels of Opportunity CAC Scoring Helps to Refine Risk Patients Undergoing CAC Scanning Have Improved Adherence to Preventive Therapies Coronary Calcium is Safe, Low Cost, Effective at Screening Women! Source: Shaw J Am Coll Cardiol 2015;65:

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28 Andersen Model of Health Services Utilization Predisposing Characteristics I. Older Age II. Higher Education Level III. Disabled IV. Extensive Comorbidity V. Perceived Well Being Perceived Barrier Reflecting Multiple Dimensions of Access Enabling Characteristics I. Employed II. Managerial Job or Higher Income III. Health Insurance IV. Urban Community V. Transportation / Social Support / Married Latent Access Barrier Classes Service Use Or Unmet Need Need Characteristics I. Presenting Symptom & Physical Exam Findings II. Risk Factor Burden III. Past Medical CV History IV. Past Medical History (non-cvd) V. Angiographic Extent & Severity of Disease Induced Testing Pattern in the Near Term Near Term Testing without Symptoms or Clear Clinical Indication PSEUDO-DISEASE DISEASE COSTS 28

29 Accelerated and Lifetime Costs From Screen-Detected Pseudo Disease Less [is More] Health Care Source: AMA / JCAHO National Summit on Overuse, Chicago, IL (Sept 2012)., Grady Arch Intern Med 2010;170(9): Judging Evidence: Weighing the Benefit & Harms of Screening Benefit: Convincing evidence that screening reduces CVD mortality Harm: Safety concerns, e.g., Radiation exposure Pain during procedures Over or under diagnosis Anxiety, distress, and other psychological responses Incidental findings False-positive & false-negative results, additional imaging, & treatment, etc. Source: :// Mark JACC 2003;41:1906., Rutter Nature Clinical Practice Endocrinology & Metabolism 2007;3:26-35., 35., Shaw JNC 2005;12:

30 Clinically Preventable Burden Model Current Post-Screening Coronary Heart Disease Deaths 697,000 10% (5%-25%) Acute Myocardial Infarction 2,100,000 25% (5%-35%) Chest Pain Symptoms 12,000,000 5% (2.5%-25%) Hospital D/C for 1 0 Diagnosis of Cardiovascular Disease Hospital D/C for 1 0 Diagnosis of Heart Failure 6,373,000 10% (5%-25%) 970,000 10% (5%-25%) Source: Naghavi M, Falk E, Hecht HS, Jamieson MJ, Kaul S, Berman D, Fayad Z, Budoff MJ, Rumberger J, Naqvi TZ, Shaw LJ, Faergeman O, Cohn J, Bahr R, Koenig W, Demirovic J, Arking D, Herrera VL, Badimon J, Goldstein JA, Rudy Y, Airaksinen J, Schwartz RS, Riley WA, Mendes RA, Douglas P, Shah PK; SHAPE Task Force. From vulnerable plaque to vulnerable patient-- Part III. Am J Cardiol 2006;98:2H-15H. Summary Induced Costs Following Coronary Artery Calcium Imaging Immediate and Far Exceeding Index Screen Cost?Pseudo-Disease Most of the CV Imaging Costs (>80%) Related to Symptom-Driven Care Unnecessary / Inappropriate Procedural Use Rate of Asymptomatic Coronary Revascularization is Low Most of the Surgical Intervention Related to Symptom-Driven Care 30

31 CONCLUSIONS (4) Start all over again Large-Scale RCTs and Registries Non-invasive CV Imaging (1) Improve the Diagnostic Workup of CAD Medical /Invasive Therapeutics A Circular Multidisciplinary Path Technology Assessment (3) Translate lessons learned to improve health outcomes Multidisciplinary Evaluation (2) Extend the Diagnostic Paradigm for CAD CV Procedural & Medication Spending Among Asymptomatic Individuals from the NIH- NHLBI-Sponsored MESA Registry $10,000 Procedural Cost $30,000 Medication Cost Cumulative CV Procedural $ $8,000 $6,000 $4,000 $2,000 $0 Year 1-3 p=ns Hs-CRP >3 mg/dl Hs-CRP 3 mg/dl Follow-up Time (in Years) p<0.001 Cumulative CV Medication $ $25,000 $20,000 $15,000 $10,000 $5,000 <0.001 p<0.001 $0 Hs-CRP >3 mg/dl Hs-CRP 3 mg/dl Follow-up Time (in Years) <

32 Probability of Annual Death from All-Causes in General Population vs. 0 CAC Score Men 0.05 Women 0.05 Probability of Annual Death Expected Mortality in General Population CAC Score Age (in years) Expected Mortality in General Population CAC Score Probability of Survival from All-Causes Life Expectancy in General Population vs. Adjusted Life Expectancy Estimates For CAC score 400 Men Adjusted Life Expectancy with CAC Score 400 General Population Life Expectancy Estimate Women Age (in years) Adjusted Life Expectancy with CAC Score 400 General Population Life Expectancy Estimate

33 Future Explorations with Atherosclerotic Plaque CAC as a Bystander Identify the Vulnerable Individual at risk for Acute Coronary Event CAD Risk Factors vs. Imaging CAC Occurs to Stabilize Plaque Non-CAC Plaque Prone to Risk High Risk Plaque Features Non-CAC Plaque, Arterial Remodeling, Treatment Implications Non-CAC (Echolucent or Low Density) Plaque Volume Reduced with Statin Treatment Source: Criqui JAMA 2014;311: , Puri J Am Coll Cardiol 2015 (in press). CAC as A Bystander: Plaque (HU) Density & CV Event Risk Hazard Ratio (95% CI) ( ) ( ) ( ) Volume Score Quartiles Source: Criqui JAMA 2014;311: ( ) ( ) 2.55 ( ) 2.98 ( ) 3.51 ( ) Density Score Quartiles 33

34 Cumulative Rates of Follow-up Invasive Coronary Angiography in CAC Cumulative Rate CAC 1,000 CAC CAC CAC CAC Years of Follow-up Year 1 Year 2 Year 4 Year 6 CAC 0-10* (n=773) CAC (n=287) CAC (n=187) CAC (n=83) CAC 1,000 (n=31) 0.3% 0.6% 1.4% 3.5% 19.5% 0.6% 1.2% 2.9% 4.6% 23.7% 0.8% 1.5% 4.2% 10.1% 33.9% 1.2% 2.2% 4.8% 13.5% 36.7% Source: Shaw JACC 2009;54: EISNER Trial: Comparisons of Costs in No Scan vs. 0 CAC Score Cost Efficiency: 4-y Costs $4,000 $3,500 $3,000 $2,500 $2,000 $1,500 $1,000 $500 $0 $3,649 No Scan p=0.001 (n=675) Source: Rozanski JACC 2011;57: $2,623 0 CAC Score Scan (n=631) Significant Worsening in the 4-y Framingham Risk Score for the No Scan vs. Scan Group (p=0.003) Compared to No-Scan, CAC=0 showed lower: Procedural Costs (p=0.0001), Meds (p=0.005) Lipid Lowering (p=0.02) Aspirin (p=0.002) 34

35 Primary Endpoint: Change in Framingham Risk Score ±5% CAC Scan (n=1,311) p=0.003 Source: Rozanski JACC 2011;57: EISNER Trial 0.7±5% No Scan (n=623) Risk Factor Changes Compared to No-Scan, Scan showed a net favorable in: SBP (p=0.02), LDL-Cholesterol (p=0.04), Waist Circumference for those w/ abdominal girth (p=0.01), and Weight Loss (among overweight ) (p=0.07) Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research (EISNER) Trial 2,137 eligible patients Randomized in 2:1 ratio 713 assigned to no-scan group 1,424 assigned to CAC scan group 623 had 4 year clinic evaluation 1,311 had for 4 year clinic evaluation Source: Rozanski JACC 2011;57:

36 Cumulative CV Procedural $ NIH-NHLBI NHLBI MESA Screening: Costs of CV Procedures & Medications among Asymptomatics with New Diagnosis of HTN, Dyslipidemia, & DM $10,000 $8,000 $6,000 $4,000 $2,000 $0 Cumulative Procedural Cost Year 1 p=ns Newly Detected Risk Factors No New Risk Factors Detected Follow-up Time (in Years) p<0.001 Cumulative CV Medication $ $30,000 $25,000 $20,000 $15,000 $10,000 $5,000 $0 Cumulative Medication Cost Year 1-4 p=ns No New Risk Factors Detected Newly Detected Risk Factors Follow-up Time (in Years) p<0.001 NIH-NHLBINHLBI MESA: Prevalence of Newly Detected Risk Factors (DM, Dyslipidemia, or HTN) on Index Screen Newly Diagnosed Hypertension (n=574) Newly Diagnosed Dyslipidemia (n=1,206) LDL Cholesterol 160 mg/dl HDL Cholesterol <40 mg/dl Total Chol. 240 mg/dl Glucose Findings (n=1,052) Impaired Fasting Glucose Fasting Glucose 126 mg/dl Low FRS (n=1,642) Average FRS (n=1,184) Intermediate FRS (n=1,949) High FRS (n=2,039) p value 0.9% 7% 20% 38% < % 10% 3% 7% 0.2% 5% 18% 6% 13% 0.8% 7% 23% 6% 17% 1% 8% 36% 8% 23% 7% < < < <

37 Average Costs for An Array of CVD Screening Approaches $120 $100 $80 $60 $ $40 $20 $0 $17.17 Lipid Panel Class I CVD Screen Detection Gap in Cardiovascular Disease Deaths in Thousands ~21% Decline Since % -10% -20% -30% US -21% EU -27% Years Men Women -40% -50% 37

38 10-Year Rates of Follow-up Diagnostic Testing in MESA Enrollees by CV Imaging Findings *p<0.05 High Risk CV Imaging Exercise Stress Test Low Risk CV Imaging Diagnostic Coronary Angiography High Risk CV Imaging Low Risk CV Imaging Years 1 8.4% 4.3%* 1.9% 0.5%* 2 5.3% 3.0%* 1.5% 0.3%* 3 6.1% 4.4%* 2.2% 0.5%* 4 4.6% 4.0% 1.6% 0.6%* 5 8.8% 5.4%* 1.7% 0.9%* 6 6.0% 4.5%* 1.7% 0.6%* 7 7.5% 6.0%* 2.4% 0.6%* 8 4.9% 5.0% 1.3% 0.5%* 9 6.4% 5.3% 2.0% 0.8%* % 3.6% 0.7% 0.8% 10-Year Rates of Incident CAD Based on Symptoms & Ensuing Management Strategy of Medical Management (Med Rx) or Coronary Revascularization (Revasc) For MESA Enrollees with High and Low Risk Findings on CV Imaging 20.0% p< % 10.0% 5.0% 0.0% 8.2% 4.9% 1.8% High Risk CV Imaging (n=1,728) 1.9% 1.3% 0.2% Low Risk CV Imaging (n=5,086) Symptomatic CAD - Revasc Symptomatic CAD - Med Rx Asymptomatic CAD - Revasc 38

39 World Health Organization CHOICE CHOosing Interventions that are Cost Effective CEA is one tool decision-makers can use to assess and potentially improve the performance of a health systems. It indicates which interventions provide the highest "value for money" and helps them choose interventions or programs that maximize health for the available resources. Its objectives are to: develop standardized method for CEA that can be applied to all interventions in different settings; develop and disseminate tools required to assess intervention costs and impacts at the population level; determine the costs and effectiveness of a wide range of health interventions, undertaken by themselves or in combination; assist policy makers and other stakeholders to interpret and use the evidence. Source: 39

40 BC #34 Task Force 5: Does Preclinical Screening Have Negative Effects? Procedure Complications Uncommon, Mostly Minor Incidental Findings Worry/Anxiety & Re-Testing Pulmonary Nodules Require Clinical Follow-up=2.3% up=2.3%-4.9% Knowledge of Being At Risk QOL e.g., HTN dx = QOL Economic Attractiveness Misclassification False - = e.g., ETT = Neg. w/ Delayed CAD Dx = Quite Costly False + = e.g. DM + CAC 400 ~20% No Ischemia + Observer Error Source: Mark JACC 2003;41:1906., MacMahon Guidelines for management of small pulmonary nodules detected on CT scans. Radiology 2005; 237: , Greenland Circulation 2007;115: , 26., Rutter The changing costs and benefits of screening for asymptomatic coronary heart disease in patients with diabetes. Nature Clinical Practice Endocrinology & Metabolism 2007;3:26-35., Shaw The complementary roles of nuclear cardiology and cardiac CT in the current healthcare environment. JNC 2005;12:131- Randomized Trial Evidence on CV Screening Hs-CRP - Generalized inflammatory marker - acute phase response to wide range of acute & chronic inflammatory conditions (e.g., infection, inflammatory diseases, etc.) 40

41 Technical Efficiency MEETING A GIVEN OBJECTIVE AT LEAST COST Apparently Well Population (Well persons plus those with undiagnosed disease) Screening Test Negatives Positives 41

42 Economic Scarcity & The Function of Choice Scarcity Means That We Have to Make Choices Due to Scarcity, Choices Must be Made by Consumers, Businesses, & Governments Making a Choice Involves a Trade-Off Choosing More of 1 Thing Can Only be Achieved by Giving Up Something Else in Exchange 42

43 Horizon Scanning Evidence Synthesis Evidence Need Identification Evidence Generation Strategies Interventions Conditions Populations Translation Dissemination Implementation Improvements in Healthcare Economics of Cardiovascular Screening Cost Efficiency / Effectiveness Comparing Preventive Screening with CAC vs. Other Tests - Results Have Been Variable Decision Analytic Models of Screening: What Can We Learn From Model Simulations? Source: Naghavi Am J Cardiol 2006;98:2H-15H., Shaw Can J Cardiol 2013;29:

44 Recommendation Grades Letter grades are assigned to each recommendation statement. These grades are based on the strength of the evidence on the harms and benefits of a specific preventive service. Grade A B C D I Statement Definition The USPSTF recommends the service. There is high certainty that the net benefit is substantial. The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial. The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small. The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined. Potential Global Cost Savings w/in Current Health Care System Current: High Cost Care: End-of of-life Care Hospital Care } 50% $ Hospital MD / Clinical Services $400B $571B Early Intervention Model: Shift Care To Early, Subclinical Dz Potential To Reduce High Cost Care Lives Lost 2 0 to CHD = Productivity Drug Nursing Home Home Health $115B $43B $189B Medicare Source: CMS, Office of the Actuary, National Health Statistics Group. Access date: March 22, Other Payers Health Spending ($ Billions) 44

45 Atherosclerosis: A Progressive Process Normal Fatty Streak Fibrous Plaque Occlusive Atherosclerotic Plaque Plaque Rupture/ Fissure & Thrombosis Unstable Angina MI Non-invasive tests abnormal Endothelial dysfunction and plaque progression due to risk factor exposure Blood levels of inflammatory markers (e.g., CRP) Effort Angina or Claudication Coronary Death Stroke Critical Leg Ischemia Clinically silent Clinically apparent Increasing age (years) Limited RCT Evidence on CV Screening 45

46 Imaging Markers of High Risk Atherosclerotic Plaque (HRP) & Incident Acute Coronary Syndromes Noninvasive CT Angiography Low Attenuation (Lipid-Rich) Plaque Expansive Arterial Remodeling Highly Predictive of Incident Acute Coronary Syndrome Source: Motoyama J Am Coll Cardiol 2015 (in press). CV Procedural & Medication Spending Among Asymptomatic Individuals from the NIH- NHLBI-Sponsored MESA Registry $10,000 Procedural Cost $30,000 Medication Cost Cumulative CV Procedural $ $8,000 $6,000 $4,000 $2,000 $0 Year 1-3 p=ns Hs-CRP >3 mg/dl Hs-CRP 3 mg/dl Follow-up Time (in Years) p<0.001 Cumulative CV Medication $ $25,000 $20,000 $15,000 $10,000 $5,000 <0.001 p<0.001 $0 Hs-CRP >3 mg/dl Hs-CRP 3 mg/dl Follow-up Time (in Years) <

47 Current Cardiovascular Disease Screening & Treatment is Based on Risk Factor Prediction Hazard for All-Cause Mortality for CAC Scores of as Compared to CAC of 0 Hazard Ratio (95% CI) deaths 23 deaths 53 deaths 160 deaths 240 deaths 1 year 3 years 5 years 10 years 15 years p=0.061 p=0.15 p=0.002 p=0.001 p< Predictive Models Through Varying Follow-up Time Periods 47

48 Goals of Quality Imaging Improved Quality Healthcare Improve overall quality by making health care more patient-centered, reliable, accessible, & safe Effectiveness Improve population health by supporting proven tests & interventions Efficiency Reduce healthcare cost & improve timeliness Adapted from AMA / JCAHO National Summit on Overuse, Chicago, IL (Sept 2012). Evolution of Clinical Research on Coronary Artery (CAD) Disease Acute Coronary Syndrome Stable Ischemic Heart Disease Nonobstructive CAD CV Screening TIMI Trials COURAGE, BARI, ISCHEMIA Trials PET Prognosis, CONFIRM Registries EISNER Trial, MESA Registry 48

49 NIH-NHLBI NHLBI Working Group - Identification of High-Risk Atherosclerotic Plaque Plaque Prone to Acute Events - Termed Vulnerable or High-Risk Search for Vulnerability Prior to Symptom Onset Has Been Elusive High Risk Plaque (HRP) - CT Angiography Low Density (Lipid-Rich) Plaque Expansive Arterial Remodeling Source: Fleg J Am Coll Cardiol CV Img 2012;5: , Motoyama J Am Coll Cardiol 2015 (in press). 49

50 MESA: Net Reclassification Improvement For Estimating Cardiac Events Comparative Effectiveness of Brachial Flow Mediated Dilation (FMD), Ankle Brachial Index (ABI), High Sensitivity C-Reactive Protein (Hs-CRP), Carotid Intima-Media Thickness (C-IMT) % Newly Detected Low Risk NRI = Compare Model 1 vs. Model 2 Risk Score + New Marker % Newly Detected High Risk % (±) New Low + High Risk = NRI Source: Polonsky JAMA 2010;303: , Yeboah JAMA 2012;308: ; Pencina Clin Chem Lab Med 2010;48: Assess Cardiovascular Risk to Guide Preventive Care k Factors = Age, Smoking, HTN, 2013 American College of Cardiology / redict 10 y CHD risk American Heart Association Guidelines of multiple, even mildly + risk factors UT limitations Primary in women, Prevention young men, diverse -US cohorts Estimate 10-y ASCVD Risk Atherosclerotic CV Risk Estimate 10-Year Risk Lifetime Risk No Treatment Indicated Moderate - High Intensity Statin Key Question: How Accurate is the New Risk Calculator Across Patient Subsets? imates less accurate for persons from some race/ oups (especially: American Indian, Asian, Hispanic) *ASCVD Risk=Atherosclerotic Disease Risk Prediction Using Risk Calculator Source: Goff J Am Coll Cardiol 2014;63: ,. Kavousi,JAMA 2014;311: , Stone J Am Coll Cardiol 2014;63:

51 Assess Cardiovascular Risk to Guide Preventive Care 2013 American College of Cardiology / American Heart Association Guidelines Primary Prevention Estimate 10-y CV Risk No Treatment Indicated Moderate - High Intensity Statin Estimate 10-Year CV Risk Risk Factors (Age, HTN, ) Integrated into Estimated CV Risk Widely validated BUT limitations in women, young men, diverse race / ethnicity, non-us cohorts Source: Goff J Am Coll Cardiol 2014;63: ,. Kavousi,JAMA 2014;311: , Stone J Am Coll Cardiol 2014;63: Assess Cardiovascular Risk to Guide Preventive Care New Atherosclerotic CV Risk Calculator 10-Year Risk Lifetime Risk Notable Limitations of Risk Scores in Women, Race / Ethinic Estimate 10-y or Lifetime CV Risk Potential for Imaging to Enhance Risk Detection No Treatment Indicated Moderate - High Intensity Statin 2013 American College of Cardiology / American Heart Association Guidelines Source: Goff J Am Coll Cardiol 2014;63: ,. Kavousi,JAMA 2014;311: , Stone J Am Coll Cardiol 2014;63:

52 2013 American College Assess of Cardiology Cardiovascular / Risk to Guide Preve American Heart Association Guidelines Primary Prevention Estimate 10-y CV Risk No Treatment Indicated Moderate - High Intensity Statin Estimate 10-Year CV Risk Risk Factors (Age, HTN, ) Integrated into Estimated CV Risk Widely validated BUT limitations in women, young men, diverse race / ethnicity, non-us cohorts Source: Goff J Am Coll Cardiol 2014;63: ,. Kavousi,JAMA 2014;311: , Stone J Am Coll Cardiol 2014;63: Health Policy, Evidence Development, & Efficient Utilization of Cardiovascular (CV) Imaging Economic Burden of CV Disease Evidentiary Standards for CV Screening e.g., Coronary Artery Calcium Imaging Value-Based Imaging = Effective + Efficient 52

53 NIH-NHLBI NHLBI MESA: Prevalence of Newly Detected Risk Factors, Hs-CRP >3 mg/dl, & CV Imaging Abnormalities 100% Screen + Screen - 100% Screen + Screen - 75% 50% 25% 0% 63.9% 74.4% 74.6% 25.6% 36.1% 25.4% Risk Factors Hs-CRP CV Imaging** 75% 50% 25% 0% 96.6% 3.4% ABI < % 19.3% 89.7% 10.3% C-IMT CAC 400 >0.75 mm Definitions: ABI: Ankle Brachial Index Hs-CRP: High Sensitivity C-Reactive Protein C-IMT: Carotid Intima-Media Thickness CAC: Coronary Artery Calcium Validation of Clinical Risk Factor Calculators REasons for Geographic And Racial Differences in Stroke (REGARDS) Study - Population Cohort of 30,239 Blacks & Whites Model Discrimination for Estimating CV Disease Events C Index: 0.72 (95% CI: ) Women s Health Study - Population Cohort of 27,542 Women Overestimated Risk by 40-90% African-AmericanAmerican White Source: Muntner JAMA 2014;311: , Cook JAMA Int Med 2014;174: , Ridker Lancet 2013;382:

54 High Rates of Growth for CV Imaging Current: Imaging Overuse or Duplication Eliminating Excess, Potential to Realize <30% Savings Future: Expanding Coverage Require Sizeable Hurdles in Quality of Evidence Source: Iglehart NEJM 2011;365: , Shaw J Am Coll Cardiol Img 2010; 3: , Stern Am J Med 2012;125: Strategies to Improve Population Health & Reduce Cardiovascular (CV) Disease Current Health Screening Based on Assessing Risk Factors (e.g., HTN, ) Imprecise Current Biomarker Research p value Search & Not Strategic to Effect to Healthcare System Cost, Efficiency of Use, Integration into Practice, etc. 54

55 CT Detection of Calcified Plaque Technical Reasons: Non-Contrast CT Safe, Low Dose Exposure (~1 msv) Low Cost ($69-$99) Easy to Measure: Agatston Score = Area (A) x Plaque Density (D) in Hounsfield Units (HU) Clinical Reasons: Accurate Across Manufacturers Common & w/ Age Strong Relationship to Outcome Area = 15 mm 2 Peak CT = 450 Score = 15 x 4 = 60 HU x-factor >400 4 American College of Cardiology 2014 Health Policy Statement on Use of Noninvasive CV Imaging High growth rates documented for most common imaging studies, which appear unrelated to clinical needs of the population Call for Higher Quality & Value-Based Evidence in CV Imaging High growth rates coincide w/ growing concern about medical spending & the lack of comparative effectiveness evidence to guide clinical application of CV imaging Source: Mark J Am Coll Cardiol 2014;63:

56 Contemporary Challenges in Academic Medicine Competitive Priorities: Population Health Discovery Science Opportunities Public Policies & Stakeholders (e.g., Patients) Can We Improve Preventive Care? Can a Research Mission Drive A Learning Healthcare System? How do We Develop Policies to Guide Healthcare Practice? Will it be affordable? Source: Lauer JAMA 2010;303: Strategic Vision & Integration Across All Facets of Research Biomedical Model Biomedical and Socioecological Model Bench Research Discovery Science Animal Studies Preclinical Bedside 1 st Human Studies Controlled Observations Phase 2 Clinical Patients Systematic Evidence Review Guideline Development Practices Dissemination Implementation Research Real World Population-level outcome research Implementation Science Discovery Science T1 Translation to Humans T2 Translation to Patients T3 Translation to Clinical Practices T4 Translation to Real World Settings Source: George Mensah, NHLBI 56

57 Strength of Evidence for CV Procedures from American College of Cardiology / American Heart Association Guidelines Strength of Evidence Level A: 1% Level C: 54% Level B: 45% 745 Recommendations Source: Tricoci JAMA 2009;301: Defining A High Quality Procedure Patient Preferences Quality Metrics Public Reporting Right Patient Right Procedure Decision Right Procedure Execution Right Outcome Appropriate Use Criteria Clinical Practice Guidelines Ongoing trials & evidence Performance Measures Value Equation for CV Procedures Was Right Procedure Done in Right Way w/ Right Outcome in a Timely Fashion? 57

58 Welcome to Medicare Physical Medicare Preventive Services CMS allowed to add coverage for preventive services if it determines thru national coverage determinations (NCD) - USPSTF grade A (strongly recommends) or B (recommends) rating Cardiovascular Screening Tests USPSTF Recommendations address services offered in primary care setting or referred by PCP Apply to adults with no signs or symptoms 58