Disclosures Research grant support from National Lipids, Statins - PowerPoint PPT Presentation

12/14/19 Disclosures • Research grant support from National Lipids, Statins and HIV: Institutes for Health (NIH), Centers for Disease Control (CDC) & President’s Topics in Clinical Management Emergency Plan for AIDS Relief (PEPFAR) – Medical Management of AIDS & Hepatitis – For work ongoing in East Africa related to HIV care models December 14, 2019 Vivek Jain, M.D., M.A.S. – This disclosure is unrelated to this presentation Associate Professor of Medicine Division of HIV, Infectious Diseases & Global Medicine San Francisco General Hospital University of California, San Francisco 1 2 1

12/14/19 Outline Outline • Who should be on statins? Recent guidance • Who should be on statins? Recent guidance • Practical use of statins in patients with HIV • Practical use of statins in patients with HIV – specific drug interactions withARV’s – specific drug interactions withARV’s • What can statins achieve? • What can statins achieve? – Lipid lowering, CV risk mitigation, malignancy reduction – Lipid lowering, CV risk mitigation, malignancy reduction • What downside risks do statins pose? • What downside risks do statins pose? – Diabetes?, myopathy?, cognitive changes? – Diabetes?, myopathy?, cognitive changes? • If statins don’t achieve their goals, or can’t be used, • If statins don’t achieve their goals, or can’t be used, what can ARV switching do to improve lipids? what can ARV switching do to improve lipids? • Ezetimibe and the PCSK9 inhibitors • Ezetimibe and the PCSK9 inhibitors 3 4 2

12/14/19 Older System: LDL-based goals 2013 Guidelines Changes LDL (mg/dL) Non-HDL (mg/dL) LDL toConsider • AHA/ACC guidelines Nov. 2013: Risk Category Primary target Secondary target DrugTherapy – assess risk of “hard” CV events Very High < 70 < 100 > 100 – used a new “global risk prediction score” High – recommend statins when 10-year risk is >7.5 % ³ 100 CHD or CHD RiskEquiv. < 100 < 130 (10-year risk > 20%) – consider statins when 10-year risk is 5 - 7.5% Moderately High • Controversies: ³ 130 < 130 < 160 ³ 2 Risk Factors < 100: optional < 130: optional 100–129: optional (10-year risk 10-20%) – do new guidelines mean there are many patients on statins who do not need to be? Moderate ³ 2 Risk Factors ³ 160 – do new guidelines mean many low risk patients not on < 130 < 160 (10-year risk < 10%) statins should be initiated? Low – Huge resource questions involving millions of patients ³ 190 < 160 < 190 0–1 Risk Factor 3 rd Report, National Cholesterol Education Program (NCEP), 2002 5 6 3

12/14/19 event rate 2018 Guideline Changes Controversy over new guidelines predicted by algorithm observed event rate Ridker & Cook (Lancet, 2013): 3 primary • Key Changes to new 2018 guidelines: • New calculator can overestimate risk …and prevention therefore recommend statins for too many people cohorts – Amplifies patient-clinician discussion • No statin RCT used a ‘global risk prediction score’ as an entry criterion… • Patient specific risks and benefits of statin • Smoking and HTN are major drivers of risk… but – Emphasis on early lifestyle modifications could end up being addressed by a statin rather than by habit reduction… • Diet: high vegetable, fruit, lean protein, whole grains, limit • Can have odd individual situations where statin sweets & processed fats unexpectedly is or isn’t recommended… • Exercise: 40 minutes, vigorous, 3-4 times per week • Heavily influenced by age: 41% of men and 27% of women age 60-69 have risk>10%, and many – Understand high/moderate/low intensity statins age>65 with no risk factors will meet risk criteria... however, no statin trials ever enrolled persons of – Use new updated risk calculator (“risk plus”) these ages with zero risk factors… • Still based on pooled population based risk equations; • However, new risk calculator became widely recognized “launch point” for shared decision making • Goal was to use it as a starting point to foster individualized discussions Grundy SM et al., 2018 JACC: 2018AHA/ACC Guideline on the Management of BloodCholesterol Ridker & Cook, Lancet , 2013 7 8 4

12/14/19 Overview of New 2018 Guidelines Consider many factors simultaneously • Strength of • Focus on ASCVD risk, as well as certain numeric LDL targets Recommendations • Differentiate who needs statin for ASCVD (secondary prevention) vs. inGuidelines who needs it for primary prevention • Differentiate high-intensity statin from moderate intensity statin • Screen for LDL>190 and diabetes • Calculate patient 10-year risk: is it >7.5%? • Consider whether the patient has any “risk enhancers” • Consider obtaining a coronary artery calcium score Also include in discussion • Smoking cessation • Diet • HTN control • Exercise Grundy SM et al., 2018 JACC: 2018AHA/ACC Guideline on the Management of BloodCholesterol 9 10 5

12/14/19 New Cholesterol Guidelines: Step by Step: Primary Prevention Does patient have LDL>190, DM, or age>75? Grundy SM et al., 2018 JACC: 2018AHA/ACC Guideline on the Management of BloodCholesterol 11 12 6

12/14/19 Step by Step: Step by Step: Is the patient <40 years old? Is patient age 40-75? Key Points 1. Calculate risk 2. Assess for risk enhancers 3. Foster shared decision making 4. Consider coronary calcium score 13 14 7

12/14/19 2018 Cholesterol Guidelines: 2018 CholesterolGuidelines Secondary Prevention Key Points 1. Most will warrant statin 2. Assess statin intensity 3.Think about therapy goals • Initiate statin to achieve goals 4. Consider non-statins also • Consider ezetimibe if not at goal • Consider PCSK-9 inhibitor if not at goal • Consider coronary artery calcium score in patients >40 with uncertain risk status: if ≥100 Agatson units= ASCVD risk ≥7.5% = start statin Grundy SM et al., 2018 JACC: 2018AHA/ACC Guideline on the Management of BloodCholesterol 15 16 8

12/14/19 Updated Web-based Calculator “Risk-PlusCalculator” Updated Web-based Calculator “Risk-PlusCalculator” http://tools.acc.org/ASCVD-Risk-Estimator-Plus http://tools.acc.org/ASCVD-Risk-Estimator-Plus Enter variables: Treatment Impact of therapy: Recommendations, including statin: Read out 10-year and life- And how this risk can time risk: be optimized/lowered with therapies: http://tools.acc.org/ASCVD-Risk-Estimator-Plus http://tools.acc.org/ASCVD-Risk-Estimator-Plus 17 18 9

12/14/19 Outline Statin Choices: a review When using PI’s: Most statins metabolized by CYP3A4 system ß PI’s (pravastatin & pitavastatin are not) • Who should be on statins? Recent guidance Atorvastatin use at 10-20mg Protease inhibitors inhibit/ When using INSTI’s with • Practical use of statins in patients with HIV downregulate cobi: follow PI rules Lovastatin CYP3A4 to different – specific drug interactions withARV’s degrees INSTI's PI’s à thusboost less potent statin • What can statins achieve? Pravastatin some statins to cobicistat: use at lower doses dangerous levels reduces – Lipid lowering, CV risk mitigation, malignancy reduction (use lowest dose with DRV, and can cause CYP3A4 or just give atorvastatin) rhabdomyolysis Simvastatin • What downside risks do statins pose? – Myopathy, diabetes?, cognitive changes? Fluvastatin NNRTI’s • If statins don’t achieve their goals, or can’t be used, EFV: raises CYP3A4 activity what can ARV switching do to improve lipids? EFV à can reduce statinlevels Rosuvastatin use at 5-10mg, fewest data in HIV+ patients Etravirine reduces atorvastatin, • Ezetimibe and the PCSK9 inhibitors increases fluvastatin, no change Pitavastatin can use at 4mg dose on pravastatin Grundy: Update to NCEP ATPIII GuidelinesCirculation, 2004 19 20 10

12/14/19 Statin potency in HIV+ patients: Outline Excellent, same as in HIV-negative • Retrospective study: 700 HIV+ patients, 2 large US clinics initiating statin • Who should be on statins? Recent guidance • Both atorvastatin and rosuvastatin did better than pravastatin in • Practical use of statins in patients with HIV reducing total cholesterol, LDL, TGs and non-HDLcholesterol – specific drug interactions withARV’s • Less accumulated data with rosuvastatin limits its use • What can statins achieve? – Lipid lowering , CV risk mitigation, malignancy reduction • What downside risks do statins pose? – Myopathy, diabetes?, cognitive changes? • If statins don’t achieve their goals, or can’t be used, what can ARV switching do to improve lipids? • Ezetimibe and the PCSK9 inhibitors Singh et al., Clin. Infect. Dis. , 2011 21 22 11