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Placebo-Controlled Statin Trials EXPLAINING THE DECREASE IN DEATHS - PowerPoint PPT Presentation

Robert Baron MD, MS Since the new ACC/AHA guidelines MANAGEMENT OF HIGH BLOOD and new Risk Estimator came out in CHOLESTEROL: December 2013, I have: IMPLICATIONS OF THE NEW GUIDELINES 1. Begun implementing the guidelines in some or most of


  1. Robert Baron MD, MS Since the new ACC/AHA guidelines MANAGEMENT OF HIGH BLOOD and new Risk Estimator came out in CHOLESTEROL: December 2013, I have: IMPLICATIONS OF THE NEW GUIDELINES 1. Begun implementing the guidelines in some or most of my patients Robert B. Baron MD MS 35% 2. Begun using the new ASCVD Risk Professor and Associate Dean 29% Estimator UCSF School of Medicine 3. Both 1 and 2 18% 15% 4. Have read or heard of the new guidelines and estimator but have not changed my Declaration of full disclosure: No conflict of practice 3% interest 5. Have not read or heard of the new Begun implemen... Begun using th... Both 1 and 2 Have read or h... Have not read ... guidelines 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 • Reductions in cholesterol: 1/4 Go, Circulation, 2014 simva 20-40 mg prava 40 mg prava 40 mg simva 40 mg prava 40 mg lova 80 mg 1

  2. Robert Baron MD, MS A 40 year women, in good health. In for a Prevention Of CVD in Women preventive visit. BMI, BP, diet and exercise all at ideal. What blood tests will you order to screen her for a lipid disorder? � Overwhelming majority of recommendations are the same for 1. Total cholesterol (fasting or non-fasting) women and for men 2. Total and HDL cholesterol (fasting or non-fasting) 34% 3. LDL and HDL cholesterol (fasting) � Aspirin use is a notable exception 4. LDL, HDL, and hs-CRP 26% 22% 5. No screening blood tests for lipids � But…there are gender differences in the magnitude of the absolute potential 11% benefits 7% . . . . . Mosca, Circulation 2011 . . . . . . . . . . e h b t L c d s D n g e L a n H D o l i d H L , n h n D e c e a d H l n r a l a c t a L , s o t L D o o T T D L N L USPSTF: Screening Recommendations ACC/AHA Screening � Men: � age 35 and older, regardless of risk level � age 20 to 35, at increased risk � All adults age 21. � Women: � age 20 and older at increased risk � If not at increased risk, no recommendation (I) � Increased Risk: � tobacco use, diabetes, hypertension, obesity, and family history of premature CV disease. USPSTF Stone, Circulation 2013 2

  3. Robert Baron MD, MS A 40 year women, in good health. In for a ACC/AHA CVD Risk: Ideal preventive visit. BMI, BP, diet and exercise All of These all at ideal. No prior lipid screen. What blood tests will you order to screen her for a lipid � Total cholesterol <200 mg/dL (untreated) disorder? � BP <120/<80 mm Hg (untreated) 1. Total cholesterol (fasting or non-fasting) � Fasting blood glucose <100 mg/dL (untreated) 2. Total and HDL cholesterol (fasting or non-fasting) � Body mass index <25 kg/m2 3. LDL and HDL cholesterol (fasting) (MY CHOICE) � Abstinence from smoking 4. LDL, HDL, and hs-CRP 5. No screening blood tests for lipids � Physical activity at goal for adults >20 y of age: 150 min/wk moderate intensity, 75 min/wk vigorous intensity, or combination Mosca, Circulation 2011 � Healthy (DASH-like) diet BARON TREATMENT CONCLUSIONS: BARON TREATMENT CONCLUSIONS: OLD OLD � Patients without CHD: � Patients with CHD or CHD equivalent: • Use medications at thresholds based on LDL and risk: • Treat aggressively with statin independent of LDL level (to LDL <70 in most cases) LDL goal LDL drug threshhold High Risk (>20%) <100 ( <70 optional) ≥ 100 • Treat other risk factors aggressively as well, especially easy ones (HTN, Aspirin use) Mod high risk (10-20%) <100 ≥ 130 Moderate risk (<10%) <100 ≥ 160 • Little evidence that adding a second drug (if on Low risk (no risk factors) <100 ≥ 190 statin) adds benefit • Patients at high risk are undertreated. Maximize adherence and avoid clinical inertia 3

  4. Robert Baron MD, MS BARON TREATMENT CONCLUSIONS: 2013 ACC/AHA Guidelines OLD What is New? � Patients without CHD: � 4 groups of patients who benefit from statins � Identifies high and moderate intensity statins • Use medications at thresholds based on risk: � No LDL treatment targets ASA STATIN High Risk (>20%) YES YES � Non-statin therapies no not provide acceptable Mod high risk (10-20%) YES YES risk reduction Moderate risk (<10%) NO Occasional YES � Estimate 10-year ASCVD risk with new equation Low risk (no risk factors)NO Usually NO Stone, Circulation 2013 Heart Protection Study: Vascular 2013 ACC/AHA Guidelines Events by Baseline LDL-C Four Groups of Patients Who Benefit From Statins No. Events � Individuals with clinical ASCVD Risk Ratio and 95% Cl Statin Placebo Baseline Statin better Statin Feature (10,269) (10,267) worse � Individuals with primary elevations of LDL ≥ 190 LDL (mg/dL) 285 360 <100 � Individuals age 40-75 with diabetes and LDL ≥ 100 <130 670 881 ≥ 70 ≥ 130 1087 1365 24% reduction ( p <0.00001) � Individuals without ASCVD or diabetes, age ALL PATIENTS 2042 2606 (19.9%) (25.4%) 40-75, with LDL ≥ 70, and 10 year risk 7.5% or higher 0.4 0.6 0.8 1.0 1.2 1.4 Stone, Circulation 2013 4

  5. Robert Baron MD, MS 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 intensity statin if risk over 7.5% � Treat with: high intensity statin, or moderate intensity statin if > age 75 � Individuals without ASCVD or diabetes, 40-75, with LDL ≥ 70, and 10 year risk 7.5% or higher: � Individuals with primary elevations of LDL ≥ 190: � Treat with: moderate-to-high intensity statin � Treat with: high intensity statin Stone, Circulation 2013 Stone, Circulation 2013 2013 ACC/AHA Guidelines TREATING TO NEW TARGETS (TNT) High Intensity vs. Moderate Intensity Statin • RCT of 10,001 patients with stable CHD; 35-75 yr � High Intensity: lowers LDL by >50% • LDL <130 mg/dl � Atorvastatin 40 - 80 � Rosuvastatin 20 - 40 • Atorvastatin 10 vs atorvastain 80 � Moderate Intensity: lowers LDL by 30-50% • Followed for 4.9 years � Atorvastatin 10 - 20 � Rosuvastatin 5 – 10 • Research question: safety and efficacy of � Simvastatin 20 - 40 lowering LDL below 100 mg/dl � Pravastatin 40 – 80 � Lovastatin 40 Stone, Circulation 2013 Larosa NEJM, 2005 5

  6. Robert Baron MD, MS TREATING TO NEW TARGETS (TNT) LDL Event % Death % ↑ LFTs % Atorv 10 101 10.9 2.5 0.2 Atorv 80 77 8.7 2.0 1.2 p value <0.001 0.09 How Best To Calculate 10 Year Risk? How Best To Calculate 10 Year Risk? Old issues Old issues � Hard vs. hard + soft CHD end points (angina) � CHD or CVD � Insufficient shared decision � Include diabetes or not making � Include peripheral vascular disease or not � Race/ethnicity (usually not) � Include family history and hs-CRP (Reynolds) � Ranges vs. exact numbers � Paper vs. computer vs. phone 6

  7. Robert Baron MD, MS How Best To Calculate 10 Year Risk? Pooled Cohort Risk Assessment Equations New Age � Pooled Cohort Risk Assessment Equations: hard Gender � CHD events and stroke Race (White/African American) � Total cholesterol (170 mg/dl) � http://my.americanheart.org/professional/StatementsGuid � elines/PreventionGuidelines/Prevention- HDL cholesterol (50 mg/dl) � Guidelines_UCM_457698_SubHomePage.jsp Systolic BP (110 mmHg � � http://www.cardiosource.org/en/Science-And- Yes/no meds for BP � Quality/Practice-Guidelines-and-Quality-Standards/2013- Yes/no DM Prevention-Guideline-Tools.aspx � Yes/no cigs � � http://clincalc.com/Cardiology/ASCVD/PooledCohort.aspx Outcome: 10-year risk of total CVD (fatal and non-fatal MI and � stroke) Do the Pooled Cohort Risk Assessment Equations Overestimate Risk? Ridker PM, Cook NR, Lancet Nov 19, 2013 Pencina MJ et al. N Engl J Med 2014. 7

  8. Robert Baron MD, MS How Best To Calculate 10 Year Risk? Baron approach April 2014 63 yo woman; s/p MI � Use both CHD (hard end points) calculator and new CV risk LDL 115 calculator HDL 45 � Include both in shared decision- TG 160 making discussion 2013 ACC/AHA Guidelines The best next step in lipid What Statin for Each Group? management is: 1. Atorvastatin 40 mg � Individuals with clinical ASCVD: 2. Rosuvastatin 10 mg 91% 3. Pravastatin 40 mg � Treat with: high intensity statin, or moderate 4. Simvastatin 40 mg intensity statin if > age 75 5. Lovastatin 40 mg 6. Whatever works to get her LDL below 70 mg/dl 6% 2% 2% 0% 0% . . . . . . . . . . . . . . . . 4 . 1 0 0 s . 0 4 4 4 k n n r i i n n o t t n a a t i i i w t t t t a a a s s t t r a a s s t e v v a a s a v Stone, Circulation 2013 r u v v e o a m v t s o a t o r A R P i L h S W 8

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