CVD Risk Assessment and Prevention in 2019 and Beyond: How, When, - PDF document

CVD Risk Assessment and Prevention in 2019 and Beyond: How, When, and Why? Donald M. Lloyd‐Jones, MD ScM FACC FAHA Eileen M. Foell Professor Chair, Dept. of Preventive Medicine Senior Associate Dean Director, NUCATS Institute Northwestern Feinberg School of Medicine Disclosures • Dr. Lloyd‐Jones has no RWI/COI  Grant funding: NIH, CMS, AHA • Members of the 2018 Cholesterol Guidelines and 2019 Primary Prevention Guidelines Panels had no RWI/COI

Case 52‐year‐old South Asian male presents for routine follow‐up • PMH: CKD (eGFR 50 mL/min/1.73 m 2 ), HTN • SH: denies tobacco, alcohol • Meds: lisinopril 10 mg PO daily • BP 142/86 mm Hg; Waist 42” • Lipids (mg/dL): TC 225 HDL‐C 35 LDL‐C 150 TG 200 • 10‐yr ASCVD risk 9.7% Case Question #1: According to the 2018 ACC/AHA cholesterol and 2019 primary prevention guidelines, which risk category is most applicable for this patient? A. Low risk primary prevention B. Borderline risk primary prevention C. Intermediate risk primary prevention D. High risk primary prevention

Case Question #2: According to the 2018 ACC/AHA cholesterol and 2019 primary prevention guidelines, which initial treatment strategy should be considered for this patient? A. Lifestyle modifications only B. Lifestyle modifications + moderate‐intensity statin C. Lifestyle modifications + high‐intensity statin D. Lifestyle modifications + high‐intensity statin + ezetimibe Topics • Rationale and evidence base for quantitative risk assessment • Current guideline recommendations • Strengths/limitations of existing risk scores • Refining risk estimates for individual patients  Clinician‐patient discussion  Risk‐enhancing factors  Measurement of CAC • Implementing risk assessment and shared decision making – practical approaches

Lloyd‐Jones et al. Circulation 2019; JACC 2019 Rationale for Absolute Risk Estimation Blood Pressure Cholesterol Lowering Treatment Trialists Treatment Trialists • Allows identification of patients at sufficient risk to merit treatment with higher likelihood of net individual and societal benefit • Allows direct comparison of potential benefits and harms from drug therapy CTT, Lancet 2012 BPLTTC, Lancet 2014 Lloyd‐Jones et al., Circ and JACC 2018

Evidence Base for Risk Estimation • Providing CVD risk score data had statistically significant but modest effects on: • Initiation/intensification of BP and cholesterol medications • Levels of CVD risk factors • Estimated 10‐year CVD risk at follow‐up • Harm very unlikely • Use of validated, quantitative risk assessment scores appears to be appropriate, safe, and moderately efficacious in helping to control risk factors … with the potential for additional value to improve decision‐making Karmali et al., Cochrane Reviews 2017 Lloyd‐Jones et al., Circ and JACC 2018 2017 ACC/AHA Hypertension Guidelines

2018 AHA/ACC/Multi‐Specialty Cholesterol Guidelines 2018 AHA/ACC/Multi‐specialty Cholesterol Guidelines Primary Prevention Recommendations for Adults 40 to 75 Years of Age With LDL levels 70 to 189 mg/dL Referenced studies that support recommendations are summarized in Online Data Supplement 16. COR LOE Risk Assessment‐Related Recommendations For the primary prevention of clinical ASCVD* in adults 40 to 75 years of age without diabetes mellitus and with an LDL‐C level of 70 to 189 mg/dL (1.7 to 4.8 mmol/L), the 10‐year ASCVD risk of a first “hard” ASCVD event (fatal and nonfatal MI or stroke) should be estimated by using the I B‐NR race‐ and sex‐specific PCE, and adults should be categorized as being at low risk (<5%), borderline risk (5% to <7.5%), intermediate‐risk (  7.5% to <20%), and high‐risk (  20%). Clinicians and patients should engage in a risk discussion that considers risk factors, adherence to healthy lifestyle, the potential for ASCVD risk‐reduction benefits, and the potential for I B‐NR adverse effects and drug–drug interactions, as well as patient preferences, for an individualized treatment decision. In intermediate‐risk adults, risk‐enhancing factors favor initiation or intensification of statin IIa B‐R therapy. In intermediate‐risk or selected borderline‐risk adults, if the decision about statin use remains IIa B‐NR uncertain, it is reasonable to use a CAC score in the decision to withhold, postpone or initiate statin therapy.

Approach to Risk Assessment in 1 o Prevention Estimate Absolute 10‐year ASCVD Risk Calculate Low Risk Borderline Risk Intermediate Risk High Risk 0 ‐ <5% 5% ‐ <7.5% ≥20% 7.5% ‐ <20% Clinician‐patient discussion considering Personalize risk‐enhancing factors and net benefit of therapy If uncertainty or patient indecision remains, Reclassify consider CAC score and revise decision based on results Lifestyle Lifestyle modification and drug therapy C= Calculate: Use Pooled Cohort Equations for ASCVD Risk Estimation • Recommended for use based on:  Broad utilization and desired endpoint of hard ASCVD  Most widely validated score in contemporary US populations • SR identified 23 manuscripts evaluating PCE in diverse populations  PCE are well calibrated near decision thresholds (e.g., 7.5% 10‐year risk) in broad US clinical population  As with all risk scores, PCE can under‐ and over‐estimate true risk in some subgroups  Reclassification by CAC well understood • New recommendations ‐ Deploy PCE with:  Expanded clinician‐patient discussion with consideration of risk‐enhancing factors  Judicious use of CAC measurement in intermediate risk and selected borderline risk patients to reclassify risk

Performance of Pooled Cohort Equations in Diverse Population Samples: Predictable Broad US Clinical Population High SES, Low SES, HIV, engaged patients Inflammatory dz Reasonable Over‐ ‐ Under‐ Under‐ Calibration Estimate Estimate Risk Risk Estimated 10-y ASCVD Risk Clinician-Patient Discussion C = Calculate: Tools for Risk Estimation • Pooled Cohort Equations – App or Online (or EHR programmable) • ACC ASCVD Risk Estimator Plus (online/app)  http://tools.acc.org/ASCVD‐Risk‐Estimator‐Plus/#!/calculate/estimate/ • AHA ASCVD Risk Calculator (online/app)  http://static.heart.org/riskcalc/app/index.html#!/baseline‐risk

Guideline Clinical App To download app search for “ACC Guideline Clinical App” in your app store

P = Personalize: Refine Risk for Individual Patients Estimate Absolute 10‐year ASCVD Risk Low Risk Borderline Risk Intermediate Risk High Risk 0 ‐ <5% 5% ‐ <7.5% 7.5% ‐ <20% ≥20% Clinician‐patient discussion considering risk‐enhancing factors and net benefit of therapy Lifestyle Lifestyle modification and drug therapy P = Personalize: Refine Risk for Individual Patients Risk‐Enhancing Factors • Family hx of premature ASCVD • High‐risk race/ethnic groups • 1 o hypercholesterolemia (LDL‐C • Lipid/biomarkers  1 o hypertriglyceridemia 160‐189 mg/dL)  If measured: • Metabolic syndrome • Chronic kidney disease Elevated hs‐CRP ≥2 mg/L • Chronic inflammatory conditions Elevated Lp(a) ≥50 mg/dL (RA, psoriasis, HIV) Elevated apoB ≥130 mg/dL • Hx premature menopause or ABI <0.9 pregnancy‐associated risk conditions

R = Reclassify Risk in Selected Patients Estimate Absolute 10‐year ASCVD Risk Low Risk Borderline Risk Intermediate Risk High Risk 0 ‐ <5% 5% ‐ <7.5% ≥20% 7.5% ‐ <20% Clinician‐patient discussion considering risk‐enhancing factors and net benefit of therapy If uncertainty or patient indecision remains, consider CAC score and revise decision based on results Lifestyle Lifestyle modification and drug therapy R = Reclassify Risk in Selected Patients 10‐year risk 5% ‐ <7.5% or 7.5% ‐ <20% Decision for No Drug Therapy Engage patient in discussion Consider risk‐enhancing regarding net benefit of statin Decision factors therapy Decision for Drug Therapy Patient Undecided or Clinical Uncertainty Regarding Net Benefit of Statin Therapy See ACC/AHA 2018 Guideline Consider CAC measurement for Cholesterol Management If performed: CAC 1 – 99 and <75 th CAC ≥ 100 or ≥75 th CAC = 0 %ile for age/sex race %ile for age/sex/race Subclinical atherosclerosis present; risk estimate Below Threshold for Statin Benefit similar. Repeat clinician‐patient discussion with new Above Threshold for Statin Benefit Consider avoiding or information. Consider statin therapy now or postpone Recommend statin therapy. postponing drug therapy.* statin and consider repeat CAC in 5 years *Clinicians and patients may not wish to postpone therapy in patients with a CAC score of 0 and diabetes mellitus, heavy current cigarette smoking, or strong family history of premature ASCVD.

Reclassification of Risk by CAC Example: MESA Study 7.5% 10‐year risk Threshold for considering statin Nasir et al., MESA Study, JACC 2015 Reclassification of Risk by CAC Example: MESA Study Identifies pts with event rates below net statin benefit range Nasir et al., MESA Study, JACC 2015