Robert Baron MD, MS Management of Lipid Disorders MANAGEMENT OF LIPID DISORDERS: Maximizing Benefits and Minimizing Harms Disclosure No relevant financial Robert B. Baron, MD MS relationships Professor and Associate Dean UCSF School of Medicine baron@medicine.ucsf.edu Placebo-Controlled Statin Trials EXPLAINING THE DECREASE IN DEATHS FROM CVD Reductions in Major Coronary Events Relative to Placebo 1980 to 2000: death rate fell by approximately 50% in both men and women 2000 to 2010: Death still falling: down 31% • About 1/2 from acute treatments, 1/2 from risk factor modification: • Predominantly cholesterol (1/4), BP, smoking simva 20-40 mg prava 40 mg prava 40 mg simva 40 mg prava 40 mg lova 80 mg 1
Robert Baron MD, MS Management of Lipid Disorders Heart Protection Study: Vascular 2013 ACC/AHA Guidelines Events by Baseline LDL-C What is New? � 4 groups of patients who benefit from statins No. Events Risk Ratio and 95% Cl Baseline Statin Placebo � Identifies high and moderate intensity statins Statin better Statin Feature (10,269) (10,267) worse � No LDL treatment targets LDL (mg/dL) <100 285 360 � Non-statin therapies no not provide acceptable ≥ 100 <130 670 881 risk reduction ≥ 130 1087 1365 24% reduction � Estimate 10-year ASCVD risk with new equation ( p <0.00001) ALL PATIENTS 2042 2606 (19.9%) (25.4%) 0.8 1.0 1.2 1.4 0.4 0.6 2013 ACC/AHA Guidelines 2013 ACC/AHA Guidelines Four Groups of Patients Who Benefit From Statins Importance of Lifestyle Recommendations � Individuals with clinical ASCVD � Heart healthy diet � Individuals with primary elevations of LDL � Regular aerobic exercise ≥ 190 � Desirable body weight � Individuals age 40-75 with diabetes and LDL ≥ 70 � Avoidance of tobacco � Individuals without ASCVD or diabetes, age 40-75, with LDL ≥ 70, and 10 year risk 7.5% or higher 2
Robert Baron MD, MS Management of Lipid Disorders Heart Healthy Diet 2016 Saturated Fat 2016 � Observational studies: no association � Two dietary factors increase LDL: between sat fat and CVD � Saturated fat � But: RCTs that replace sat fat with unsat fat reduce total and LDL � Total Calories cholesterol and CVD events and � Restriction of dietary cholesterol is mortality no longer recommended (Dietary � And: replacing sat fat with carb reduces Guidelines 2015) total and LDL cholesterol but increases triglycerides and HDL and does not lower CVD events 2013 ACC/AHA Guidelines 2013 ACC/AHA Guidelines What Statin for Each Group? What Statin for Each Group? � Individuals 40-75 with diabetes and LDL ≥ 70: � Individuals with clinical ASCVD: � Treat with: moderate intensity statin, or high � Treat with: high intensity statin, or moderate intensity statin if risk over 7.5% intensity statin if > age 75 � Individuals without ASCVD or diabetes, 40- � Individuals with primary elevations of 75, with LDL ≥ 70, and 10 year risk 7.5% or higher: LDL ≥ 190: � Treat with: high intensity statin � Treat with: moderate-to-high intensity statin 3
Robert Baron MD, MS Management of Lipid Disorders 2013 ACC/AHA Guidelines How Best To Calculate 10 Year Risk? High Intensity vs. Moderate Intensity Statin � High Intensity: lowers LDL by >50% Pooled Cohort Risk Assessment Equations: hard � Atorvastatin 40 - 80 CHD events and stroke � Rosuvastatin 20 - 40 � http://my.americanheart.org/professional/State � Moderate Intensity: lowers LDL by 30-50% mentsGuidelines/PreventionGuidelines/Preventi � Atorvastatin 10 - 20 on-Guidelines_UCM_457698_SubHomePage.jsp � Rosuvastatin 5 – 10 � Simvastatin 20 - 40 � Pravastatin 40 – 80 � Lovastatin 40 Do the Pooled Cohort Risk Assessment Pooled Cohort Risk Assessment Equations Equations Overestimate Risk? Age � Gender � Race (White/African American) � Total cholesterol (170 mg/dl) � HDL cholesterol (50 mg/dl) � Systolic BP (110 mmHg � Yes/no meds for BP � Yes/no DM � Yes/no cigs � Outcome: 10-year risk of total CVD (fatal and non-fatal MI and � stroke) 4
Robert Baron MD, MS Management of Lipid Disorders Percent of U.S. Adults Who Would Be Eligible for Statin Therapy for How Best To Calculate 10 Year Risk? Primary Prevention, According to Set of Guidelines and Age Group. Baron Approach Spring 2016 � Use both CHD (hard end points) calculator and new CV risk calculator � Include both in shared decision- making discussion Pencina, N Engl J Med 2014 How Best To Calculate 10 Year Risk? Mayo Clinic Statin Choice Decision Aid: 63 yo woman; s/p MI LDL 115 � http://statindecisionaid.mayoclinic.org/ind ex.php/statin/index?PHPSESSID=0khk8n HDL 45 m14h9vubjm3423e6h6b2 TG 160 5
Robert Baron MD, MS Management of Lipid Disorders 2013 ACC/AHA Guidelines The best next step in lipid What Statin for Each Group? management is: 89% A. Atorvastatin 40 mg � Individuals with clinical ASCVD: B. Rosuvastatin 10 mg C. Pravastatin 40 mg � Treat with: high intensity statin, or moderate D. Simvastatin 40 mg intensity statin if > age 75 E. Lovastatin 40 mg F. Whatever works to get her LDL 8% below 70 mg/dl 1% 1% 1% 0% g g g g g m m m m m . . 0 0 0 0 0 . t 4 1 4 4 4 e n g n n n n i i i i i t t t t t o a a a a a t t t t t t s s s s s s k a a a a a v v v r v v o r u a m o o w s r L t o P i A S r R e v e t a h W The best next step in lipid 63 yo woman; s/p MI. On management is: atorvastatin 80. 1. Atorvastatin 40 mg LDL 95 2. Rosuvastatin 10 mg HDL 40 3. Pravastatin 40 mg 4. Simvastatin 40 mg TG 200 5. Lovastatin 40 mg 6. Whatever works to get her LDL below 70 mg/dl 6
Robert Baron MD, MS Management of Lipid Disorders Summary Lipid-Lowering Drugs The best next step in lipid management is: • Statins are treatment of choice based on RCT to decrease risk 68% A. Continue current therapy B. Switch to rosuvastatin 40 mg • No evidence to support adding niacin or C. Add fenofibrate fibrates to statins D. Add fish oil E. Add niacin • If completely statin-intolerant, niacin may 12% F. Add ezetimibe 8% reduce CVD risk (weak evidence) 6% 4% 2% l n e y e i t o i b p . c . a a i a n r h m b i r i s n i • Fibrates appear to lower MI risk, but no other e t i i t f f h a o d e t d z t n d d s e t a e A n v A d f e u d r d s A r d CVD endpoints u o r A c o e t u h n c t i t n i w o C S Summary Lipid-Lowering Drugs PCSK9 Inhibitors • Ezetimibe study: (IMPROVE-IT) � Evolocumab (Repatha) and alirocumab (Praluent)—monoclonal antibodies that reduce liver LDL-receptor degradation 18,000 ACS patients (40% from North America) RCT: Simvastatin vs simvastatin + ezetimibe. � Reduce LDL by 50%. Injectable Q2 – 4 weeks Took 7 years. Death, MI, Stroke � Approved for FH or patients with CVD “who need Simvastatin: 34.7% vs Simva/ezetimibe 32.7% additional LDL lowering.” (270 fewer events over 7 years) � Unproven cardiovascular benefits 7
Robert Baron MD, MS Management of Lipid Disorders 63 yo woman, no traditional risk The best next step in lipid factors management is: LDL 155 HDL 55 1. Continue current therapy TG 160 2. Switch to rosuvastatin 40 mg (Also potentially SBP 120 correct, but medication still on patent) 3. Add fenofibrate No BP meds 4. Add fish oil No DM 5. Add niacin Nonsmoker 6. Add ezetimibe The best next step in lipid 63 yo woman, no risks management is to calculate 10 year risk and: LDL 155, HDL 55, TG 160 A. Continue current therapy (no meds) SBP 120, No BP meds B. Begin atorvastatin 40 64% Nonsmoker, No DM C. Begin atorvastatin 10 D. Begin simvastatin 20 10 yr CHD risk (old calculator): 2%… E. Begin sustained release niacin 30% 10 yr CV risk (new calculator): 4.5%… F. Begin red yeast rice 6% 1% 0% 0% 0 0 0 e . 4 1 2 . c Therefore no medication recommended . . p . n n . r i n n a i i i t t t t e s r a a a s e a h t t t a e s s s e t a a a y v e l t v v d n r r m r e o o e i d r r t t s e r a a n u n i n n n g c a i i i g i e e g g t B e e e s u B u n B B s i t n n g i o C e B 8
Robert Baron MD, MS Management of Lipid Disorders The best next step in lipid 63 yo man, no traditional risk management is to calculate 10 factors year risk and: A. Continue current therapy (no meds) LDL 155 B. Begin atorvastatin 40 HDL 55 63% C. Begin atorvastatin 10 TG 160 D. Begin simvastatin 20 SBP 120 E. Begin sustained release niacin 17% 19% No BP meds F. Begin red yeast rice No DM 1% 0% 0% 0 0 0 e . 4 1 2 . . c . . . Nonsmoker p n n r i n n a i i i t r t t t e s a a a s e a h t t t a e s s s e t a a a y v e l t v v d n r r m r o o e e d r r t t i r a a s e n n u n n n i c i g i i i a e e g g g t e e e s B u B B B u n s i t n n i o g e C B 63 yo man, no risks LDL 155, HDL 55, TG 160 SBP 120, No BP meds Nonsmoker, No DM 10 yr CHD risk (old calculator): 10%… 10 yr CV risk (new calculator): 10.8%… “Toss-up.” Shared decision making. If start statin (per new guidelines), can start with moderate intensity statin 9
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