Khurram Nasir, MD MPH

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Non-invasive CAD Screening Khurram Nasir, MD MPH Disclosures I have no relevant commercial relationships to disclose, and my presentation will not include off label or unapproved usage. HOW & WHAT WOULD YOU DECIDE? 60 white Male T Chol: : 182 mg/dl HDL: 40 mg/dl TG: 152 mg/dl HTN on ACEI SBP 125 mm Hg Non diabetic FH of premature CVD Hs-CRP: 3.1 mg/l 1

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Step 1: Start with ASCVD Risk Calculation Age (years) 20-79 Gender Male Female Race African American Other Total cholesterol (mg/dl) 130-320 HDL cholesterol (mg/dl) 20-100 Systolic blood pressure (mmhg) 90-200 Diastolic blood pressure (mmhg) 30-140 Treated for high blood pressure No Yes Diabetes No Yes Smoker No Yes Calculate ASCVD RISK IS 12%: WHAT WOULD YOU DO NOW? 60 white Male T Chol: : 182 mg/dl HDL: 40 mg/dl TG: 152 mg/dl HTN on ACEI SBP 125 mm Hg Non diabetic FH of premature CVD Hs-CRP: 3.1 mg/l ASCVD Risk: 12% Framingham Risk: 11% Reynold Risk: 15% 3

Challenges with Risk Assessment & Management Guidelines in 2015 Out of 101 million adults free of ASCVD in US, 33 million (recommended) and 12 million (considered) for statin 1 billion individuals worldwide candidates for statin Generic cost for statins 1 trillion dollars in 2020 Systematic overestimation of risk is a significant concern if it leads to prescription of statin therapy (and its potential adverse effects) among groups in which actual risk scores are lower than predicted. (Ridker P et al Ann Intern Med 2015) Two third patients averse to taking long term medication unless at high risk and substantial benefit. (Fontana M et al, Circulation 2015) 4

Computed Tomography for Non-Invasive Imaging of Subclinical Coronary Atherosclerosis Imaging of coronary artery calcification as a specific sign of atherosclerosis Agatston AS, Janowitz WR et al. Quantification of coronary artery calcium using ultrafast computed tomography. JACC 1990 WOULD YOU CONSIDER CAC TEST? 60 white Male T Chol: : 182 mg/dl HDL: 40 mg/dl TG: 152 mg/dl HTN on ACEI SBP 125 mm Hg Non diabetic FH of premature CVD Hs-CRP: 3.1 mg/l ASCVD Risk: 12% Framingham Risk: 11% Reynold Risk: 15% 5

Looking upside down: what is value of absence of CAC? Study Type Population (n) CAC=0 (%) FU (Years) Number of events (%) Meta-Analysis * 71,595 29,312 (41%) Retrospective** 44,052 19,898 (45%) Prospective*** 6,809 3,414 (50%) 4.3 154 (0.47%) CVD events 5.6 104 (0.52%) Deaths 4.1 17 (0.52%) CHD events *Sarwar A, Shaw LJ, Shapiro MD, Blankstein R, Hoffman U, Brady TJ, Cury R, Budoff MJ, Blumenthal RS, Nasir K. JACC Imaging 2009 ** Blaha M, Budoff MJ, Shaw LJ, Khosa F, Rumberger JA, Berman D, Callister T, Raggi P, Blumenthal RS, Nasir K. JACC Imaging 2009 *** Budoff M, McClelland R, Nasir K, Greenland P, Kronmal RA, Kondos G, Shea S, Lima JAC, Blumenthal RS. Am Heart J 2009 WOULD YOU CONSIDER TO RULE OUT DISEASE? 60 white Male T Chol: : 182 mg/dl HDL: 40 mg/dl TG: 152 mg/dl HTN on ACEI SBP 125 mm Hg Non diabetic FH of premature CVD Hs-CRP: 3.1 mg/l ASCVD Risk: 12% Framingham Risk: 11% Reynold Risk: 15% 6

European Heart Journal doi:10.1093/eurheartj/eht508 CLINICAL REASEARCH Prevention and epidemiology Impact of coronary artery calcium on coronary heart disease eventsin individualsat the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis Circulation. 2014;129:77-86; Michael G. Silverm an 1,2, Michael J. Blaha 1, Harlan M. Krum holz 3, Matthew J. Budoff 4, Ron Blankstein 2, Christopher T. Sibley 5, Arthur Agatston 6, Roger S. Blum enthal 1, and Khurram Nasir 1,6,7,8* European Heart Journal doi:10.1093/eurheartj/eht508 CLIN ICAL REASEARCH Prevention and epidemiology Impact of coronary artery calcium on coronary heart disease eventsin individualsat the extremes of traditional risk factor burden: the Multi-Ethnic Study of Atherosclerosis Circulation. 2014;129:77-86; Michael G. Silverman 1,2, Michael J. Blaha 1, Harlan M. Krumholz 3, Matthew J. Budoff 4, Ron Blankstein 2, Christopher T. Sibley 5, A rthur Agatston 6, Roger S. Blum enthal 1, and Khurram Nasir 1,6,7,8* 7

Are all Diabetics Equivalent? Malik S, Budoff M, Katz R, Blementhal RJ, Alain Bertoni, Blumenthal RS, Nasirk K, Szklo M, Barr G, Wong ND ( Diabetes Care 2012) 25% 47% 28% 75% of all events occurred in 25% with CAC>100 Number needed to treat: CAC 0 549 CAC 1-100 94 CAC > 100 24 Risk Factors Does Not Equate Presence and Burden of Atherosclerosis Huge Heterogeneity Exists even at spectrum of Traditional Risk Profile 8

ANY VALUE FOR CAC IN NEW GUIDELINES? 60 white Male T Chol: : 182 mg/dl HDL: 40 mg/dl TG: 152 mg/dl HTN on ACEI SBP 125 mm Hg Non diabetic FH of premature CVD Hs-CRP: 3.1 mg/l 4 QUESTIONS How Many Adult Without Established ASCVD Will be Candidates for Statins? 9

What is the probability of CAC=0 across statin recommendation groups? 10

Will CAC=0 lower risk below threshold where statins are recommended? Is CAC testing useful across the entire spectrum of risk categories? 11

Challenges with CAC Testing in 2016 http://nyti.ms/1nh3dwf HEALTH Heart Scan Can Fine-Tune Risk Estimate for Patients Considering Statins By GINA KOLATA OCT. 5, 2015 12

Does CAC Testing Has Such a Dramatic Downstream Impact? Downstream Tests No-CAC Testing (n = 623) CAC Testing (n = 1,311) P value Stress Test 33.9% 34.6% 0.74 Cardiac CT 7.1% 7.7% 0.62 Cardiac Catherization 2.9% 3.3% 0.71 Coronary Revascularization 1.8% 2.3% 0.46 Downstream Costs EISNER STUDY: 4 YEAR FOLLOW-UP Median Procedure costs* $721 $904 0.56 Median Medication costs $2,937 $3,149 0.09 *Include $150 for CAC testing. Rozanski et al, J Am Coll Cardiol. 2011;57:1622-1632 How Can We Incorporate CAC Testing (especially CAC=0) in Shared Decision Making? 13

Harlan Krumholz Contributor I cover science and medicine. Opinions expressed by Forbes Contributors are their own. PHARMA & HEALTHCARE 10/05/2015 @ 2:00PM 1,307 views This Test Might Tell You If You Don't Need A Statin Harlan Krumholz Contributor I cover science and medicine. Opinions expressed by Forbes Contributors are their own. PHARMA & HEALTHCARE 10/05/2015 @ 2:00PM 1,307 views This Test Might Tell You If You Don't Need A Statin Patient # 1: ASCVD 12% Patient # 2: ASCVD 12% Patient Discussion (part 1) Risk in simple terms Statin efficacy Side-effects Costs Patient Discussion (part 1) Risk in simple terms Statin efficacy Side-effects Costs Patient Discussion (part 2) Probability of CAC categories Revised Risk with CAC scores Revised Impact with Statin Use Costs Radiation Patient Discussion (part 2) Probability of CAC categories Revised Risk with CAC scores Revised Impact with Statin Use Costs Radiation CAC=0 Patients decide against CAC Patients decide against statin Patients decide for moderate dose statin 14

Op-Ed: Coronary Calcium for Informed Statin Choices It 's not about screening, says Khurram Nasir, MD, MPH Op-Ed: Coronary Calcium for Informed Statin Choices It 's not about screening, says Khurram Nasir, MD, MPH What about other tests/risk factors? 15

Circulation. 2016 Jan 22. pii: CIRCULATIONAHA.115.018524. [Epub ahead of print] Role of Coronary Artery Calcium Score of Zero and Other Negative Risk Markers for Cardiovascular Disease: The Multi-Ethnic Study Of Atherosclerosis (MESA). Blaha MJ 1, Cainzos-Achirica M 2, Greenland P 3, McEvoy JW 4, Blankstein R 5, Budoff MJ 6, Dardari Z 4, Sibley CT 7, Burke GL 8, Kronmal RA 9, Szklo M 10, Blumenthal RS 4, Nasir K 11. Abstract BACKGROUND: -Limited attention has been paid to negative cardiovascular disease (CVD) risk markers despite their potential to improve medical decision-making. We compared thirteen negative risk markers using diagnostic likelihood ratios (DLR), which model the change in risk for an individual after the result of an additional test. De-risking: Comparison of CAC=0 with Other Markers What about Costs?.Is the approach of not treating those with CAC=0 compared to current guidelines cost-effective? 16

PLOS ONE March 18 2015 CAC in 2016: The question to ask is Why Not rather than Why? Most precise measure for risk of clinical CVD event Widely available Inexpensive (75-100 $) Easy to perform (takes 2-3 minutes) and interpret Radiation equivalent to mammogram Advantages to stakeholders Health System: Appropriately allocating healthcare resources to groups likely to receive net benefit from proven Interventions. Clinician: personalized assessment of risk on case by case situation Patient: Shared decision making CAC in 2016: Who and What? Who Intermediate risk patients 5-20% undecided about statin use Patient choice driven What CAC=0 Focus on Lifestyle Intervention CAC 1-100 +Moderate/High Dose Statin CAC>100 +High Dose Statin & Aspirin CAC>400 Can consider functional testing (stress test) At no point, asymptomatic patient should be considered for invasive angiography. 17

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