PREV E E V N E TI T O I N

Transcription

1 PREVENTION OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE SHANE JOHNSON,, PHARM. D. OBJECTIVES 1. Define atherosclerotic cardiovascular disease(s) and describe the disease progression. 2. Identify three independent risk factors for atherosclerotic cardiovascular disease. 3. Understand the four treatment target groups identified in the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults. 4. Independently evaluate your lifestyle, or your family s lifestyle, and how you could potentially decrease your risk for developing cardiovascular disease. 1

2 ASCVD Definition: Progressive thickening of plaque within various arteries of the body, potentially leading to rupture and clinical disease (heart attack, stroke, peripheral artery disease). Plaque: Fat, cholesterol, calcium, and other substances in the blood Atherosclerosis starts with an acute injury to the blood vessel causes inflammatory cells to enter space between intima/media and the cells begin to oxidize LDL. Fatty Streak = First evidence of atherosclerosis. Not harmful on its own, but progressively becomes a problem. Composed of macrophages which have digested LDL within the intima. 2

3 Slower growing plaques (slower accumulation of lipid in foam cells) tend to stabilize as fibrin cap matures to contain the lipid pool. Faster growing plaques tend to have a very thin fibrin cap that is more prone to rupture

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5 REVIEW OF GUIDELINES POP QUIZ What do the new cholesterol guidelines and camping have in common? 5

6 THREE CRITICAL QUESTIONS: 1. Identify groups of patients who will benefit from pharmacological treatment. 2. Define the pharmacological treatment(s)for which there is the best evidenceof net benefit. 3. Provide guidance on the appropriate intensityof pharmacological treatment to lower LDL. 6

7 METHODS Study Inclusion: Date Range: Jan Dec *** Study Types: RCTs w/ ASCVD outcomes, or Systemic Reviews/Meta Analyses w/ ASCVD outcomes METHODS Study Inclusion: Health Outcomes Evaluated [ASCVD] Acute Coronary Syndromes History of Myocardial Infarction Stable/Unstable Angina Coronary or Other Arterial Revascularization Stroke Transient Ischemic Attack Peripheral Arterial Disease of Atherosclerotic Origin METHODS Study Exclusion: Observational Studies <18 Months Follow-Up for CQs 1 & 2 <12 Months Follow-Up for CQ 3 Populations Not Covered by Guidelines: <21 years of age NYHA Class II-IV Heart Failure Hemodialysis 7

8 LIFESTYLE MODIFICATION Heart healthy lifestyle habits are the foundation of ASCVD prevention! Heart healthy diet Regular exercise habits Avoid tobacco products Maintenance of healthy weight What s New in the Guideline? Focus on ASCVD Risk Reduction: 4 statin benefit groups Based on a comprehensive set of data from RCTs that identified 4 statin benefit groups which focus efforts to reduce ASCVD events in secondary and primary prevention. Identifies high-intensity and moderate-intensity statin therapy for use in secondary and primary prevention. A New Perspective on LDL C and/or Non-HDL C Treatment Goals The Expert Panel was unable to find RCT evidence to support continued use of specific LDL C and/or non-hdl C treatment targets. The appropriate intensity of statin therapy should be used to reduce ASCVD risk in those most likely to benefit. Nonstatin therapies do not provide acceptable ASCVD risk reduction benefits compared to their potential for adverse effects inthe routine prevention of ASCVD. Global Risk Assessment for Primary Prevention This guideline recommends use of the new Pooled Cohort Equations to estimate 10-year ASCVD risk in both white and black men and women. By more accurately identifying higher risk individuals for statin therapy, the guideline focuses statin therapy on those most likely to benefit. It also indicates, based on RCT data, those high-risk groups that may not benefit. Before initiating statin therapy, this guideline recommends a discussion by clinician and patients. Safety Recommendations This guideline used RCTs to identify important safety considerations in individuals receiving treatment of blood cholesterol to reduce ASCVD risk. Using RCTs to determine statin adverse effects facilitates understanding of the net benefit from statin therapy. Provides expert guidance on management of statin-associated adverse effects, including muscle symptoms. Role of Biomarkers and Noninvasive Tests Treatment decisions in selected individuals who are not included in the 4 statin benefit groups may be informed by other factors as recommended by the Risk Assessment Work Group guideline. Future Updates to the Blood Cholesterol Guideline This is a comprehensive guideline for the evidence-based treatment of blood cholesterol to reduce ASCVD risk. Future updates will build on this foundation to provide expert guidance on the management of complex lipid disorders and incorporate refinements in risk stratification based on critical review of emerging data. RCTs comparing alternate treatment strategies are needed in order to inform future evidence-based guidelines for the optimum ASCVD risk reduction approach. WHY IS TREAT-TO-TARGET GONE? RCT Evidence: Compares FIXED DOSE STATIN to PLACEBO Or HIGH-intensity to MODERATE-intensity No RCTs exist that compare LDL goals Non-Statin Therapies did not improved ASCVD outcomes (ACCORD, AIM-HIGH) Martinez T, Yavas D. Is the verdict finally in? Updates in cholesterol guidelines. ASHP Midyear Clinical Meeting. Orlando FL. 12 Dec Presentation. 8

9 STATIN INTENSITY TABLE High-Intensity >/= 50% LDL Reduction Moderate-Intensity 30-50% LDL Reduction Low-Intensity < 30% LDL Reduction Atorvastatin mg Atorvastatin 10 (20)mg Simvastatin 10 mg Rosuvastatin 20 (40) mg Rosuvastatin (5) 10 mg Pravastatin mg Simvastatin mg Lovastatin 20 mg Pravastatin 40 (80) mg Fluvastatin mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg BID Pitavastatin 2 4 mg Pitavastatin 1 mg Bold = Evaluate in RTCs, Italic = FDA-approved doses but not in RCTs STATIN BENEFIT GROUPS BENEFIT GROUPS: 1. Individuals with clinical atherosclerotic cardiovascular disease (ASCVD) 2. Primary elevations of LDL >/= 190 mg/dl 3. Diabetes, age with LDL mg/dl 4. All patients with LDL mg/dl and 10-year ASCVD risk >/= 7.5% (Pooled cohort equation) Clinical ASCVD: Acute coronary syndromes, history of MI, stable/unstable angina, coronary or other arterial revascularization, stroke, TIA, or peripheral arterial disease of atherosclerotic origin. GROUP 1: CLINICAL ASCVD A. Age </= 75 years: High-intensity statin [Grade: A] B. Age </= 75 years with contraindication to high-intensity statin: Moderate-intensity statin [Grade: A] C. Age > 75 years: Moderate-intensity statin [Grade: E] 9

10 GROUP 2: LDL >/= 190 MG/DL A. High-intensity statin [Grade: B] Moderate-intensityif contraindicated [Grade: B] B. Target 50% LDL reduction [Grade: E] C. Add non-statin therapy [Grade: E] Secondary Cause Elevated LDL Elevated Triglycerides Diet Drugs Diseases Metabolic disorders Saturated or trans fats, weight gain, anorexia Diuretics, cyclosporine, glucocorticoids, amiodarone Biliary obstruction, nephrotic syndrome Hypothyroidism, obesity, pregnancy Weight gain, very low-fat diets, high intake of refined carbs, excessive alcohol intake Oral estrogens, glucocorticoids, bile acid sequestrants, protease inhibitors, retinoic acid, anabolic steroids, sirolimus, raloxifene, tamoxifen, beta blockers, thiazides Nephrotic syndrome, chronic renal failure, lipodystrophies Diabetes, hypothyroidism, obesity, pregnancy GROUP 3: DIABETES + AGE A. Moderate-intensity statin [Grade: A] High-intensity statin if 10-year risk >/= 7.5% [Grade: E] 10

11 GROUP 4: 10-YEAR RISK >/= 7.5% + AGE A. Use Pooled Cohort Equation [Grade: E] B. Moderate-intensityto High-intensity statin [Grade: A] C. 10-year risk 5-7.5%: A. Offer Moderate-intensity statin [Grade: C] D. Alternative risk reduction [Grade: E] POOLED COHORT CALCULATOR calculator POOLED COHORT CALCULATOR Factors Included in the Calculator Gender SBP Age HTN Treatment Race Diabetes Total Cholesterol Smoking Status HDL Martinez T, Yavas D. Is the verdict finally in? Updates in cholesterol guidelines. ASHP Midyear Clinical Meeting. Orlando FL. 12 Dec Presentation. 11

12 HEART FAILURE& HEMODIALYSIS No recommendation on initiation or discontinuation of statin in NYHA class II-IV heart failure or patients on maintenance hemodialysis. Evidence did not show significant reduction of CVD risk in these patient groups. OTHER BIOMARKERS? NOT in other four target groups: LDL C 160 mg/dl or other evidence of genetic hyperlipidemias Family history of premature ASCVD <55 years of age in a first degree male relative <65 years of age in a first degree female relative High-sensitivity C-reactive protein >2 mg/l CAC score 300 Agatston units Or 75 percentile for age, sex, and ethnicity Ankle-brachial index <0.9 Elevated lifetime risk of ASCVD 12

13 2013 CHOLESTEROL GUIDELINE UPDATE Other cholesterol medications: Non-statin therapies do not provide acceptable ASCVD risk reduction benefits compared to their potential for adverse effects in the routine prevention of ASCVD Statin RCTs provide the most extensive evidence for the greatest magnitude of ASCVD event reduction, with the best margin of safety Non-Statin Therapy Niacin BAS Cholesterol- Absorption Inhibitors Fibrates Omega-3 Fatty Acids Recommendation Baseline: Hepatic transaminases, FBG/HgA1C, and uric acid (also at up-titration and Q6months) Do not use: Hepatic transaminases 2-3x ULN, persistent severe cutaneous symptoms, hyperglycemia, acute gout, or unexplained abdominal pain or GI symptoms, new onset A. fib or weight loss To reduce adverse cutaneous symptoms: start at a low dose and titrate over weeks, take with food or pre-meditate with ASA 325mg 30 minutes before niacin dose, start XR niacin at 500mg and increase to a max of 2g/day over 4-8 weeks increasing not more than weekly, or start IR niacin at 100mg TID and increase to 3g/day BID-TID Baseline: Fasting lipid panel (also at 3 months and Q6-12months thereafter) Do not use: Baseline fasting triglycerides 300mg/dL or type III hyperlipoproteinemia Use with caution: Baseline TGs mg/dL and evaluate a FLP in 4-6 weeks after initiation. Discontinue if TGs >400mg/dL Baseline: Hepatic transaminases If co-administered with a statin: Monitor transaminases as clinically indicated and D/C if persistent ALT >3x ULN Gemfibrozil: Do not initiate concurrently with a statin due to increased risk of rhabdomyolysis Fenofibrate: Can be considered with a low-to-moderate-intensity statin only if benefits outweigh risks in a patient with TGs >500mg/dL. Evaluate renal status at baseline, 3 months, and Q6months thereafter. Do not use: egfr <30mL/min per 1.73 m 2 Do not exceed 54mg/day: egfr 30-59mL/min For TGs 500mg/dL, evaluate patient for GI disturbances, skin changes, and bleeding if used Tsupa, A. (2013, December) ACC/AHA Blood Cholesterol Guideline. Student presentation at St. Luke s Boise Medical Center, Boise ID. SPEAKING OF HEALTHY LIFESTYLES 13

14 THREE CRITICAL QUESTIONS: 1. Among adults (18-80 years), what is the effect of dietary patterns and/or macronutrient composition on CVD risk factors, when compared to no treatment/other interventions? 2. dietary intake of sodium and potassium on CVD risk factors and outcomes, compared to no treatment/other interventions? 3. physical activity on BP and lipids, compared to no treatment/other interventions? Eckel, Robert H., et.al. "2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the ACC/AHA Task Force on Practice Guidelines. Circ.ahajournals.org. American Heart Association, 12 Nov Web. 26 Nov < EASIEST THING YOU CAN DO TODAY KEYS TO LOWERING LDL Consume more: Vegetables Fruits Whole Grains Low-Fat Dairy Products Poultry Fish Legumes Nontropical Vegetable Oils Nuts Consume less: Sweets Sugar-Sweetened Beverages Red Meats HOW? DASH Diet USDA Food Pattern AHA Diet Eckel, Robert H., et.al. "2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the ACC/AHA Task Force on Practice Guidelines. Circ.ahajournals.org. American Heart Association, 12 Nov Web. 26 Nov < 14

15 START WITH CALORIES: Male, 35 years old, 6 ft, 200 lbs, Low Active Female, 35 years old, 5 ft, 140 lbs, Low Active LDL REDUCTIONS Study Diet Control Diet Result? Decreased LDL by ~12 mg/dl, or 11%, depending on the study. If you are in a higher risk ASCVD category, limit saturated fat! Eckel, Robert H., et.al. "2013 AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the ACC/AHA Task Force on Practice Guidelines. Circ.ahajournals.org. American Heart Association, 12 Nov Web. 26 Nov < UNSATURATED FATS Mainly found in fish oils, vegetable oils, and nuts or seeds. Typically liquid at room temperature. Omega-3 Fatty Acids: Fish, Tofu, Walnuts, Flaxseed, Canola Monounsaturated/Polyunsaturated: Avocado, Nuts/Seeds, Olives, Vegetable Oils, Peanut Butter 15

16 SATURATED FATS Found in animal fats, fried foods, and some prepackaged foods. Typically solid at room temperature. Saturated Fats: Increase LDL High-Fat Cheese, High-Fat Cuts of Meat, Whole-Fat Milk/Cream, Butter, Ice Cream, Palm/Coconut Oil Trans Fats: DOUBLE WHAMMY! Processed Foods, Shortening EXERCISE Increased physical activity = Decreased risk of chronic disease, CVD, and enhanced longevity! Double-dip --- Physical activity along can have favorable effect on BP/LDL, weight loss from exercise can have additional benefit! Recommendation: Aerobic physical activity 3-4 sessions per week, 40 minutes per session Moderate-Vigorous Intensity Can break up into 10 minutes at a time! Something is better than nothing! 16

17 RISK CALCULATOR UNDER SPECULATION Kavousi M, Leening MG, Nanchen D, et al. Comparison of Application of the ACC/AHA Guidelines, Adult Treatment Panel III Guidelines, and European Society of Cardiology Guidelines for Cardiovascular Disease Prevention in a European Cohort. JAMA. 2014;():. doi: /jama RISK CALCULATOR UNDER SPECULATION C=0.67 C=0.68 Kavousi M, Leening MG, Nanchen D, et al. Comparison of Application of the ACC/AHA Guidelines, Adult Treatment Panel III Guidelines, and European Society of Cardiology Guidelines for Cardiovascular Disease Prevention in a European Cohort. JAMA. 2014;():. doi: /jama RISK CALCULATOR UNDER SPECULATION Kavousi M, Leening MG, Nanchen D, et al. Comparison of Application of the ACC/AHA Guidelines, Adult Treatment Panel III Guidelines, and European Society of Cardiology Guidelines for Cardiovascular Disease Prevention in a European Cohort. JAMA. 2014;():. doi: /jama

18 RISK CALCULATOR VALIDATION Muntner P, Colantonio LD, Cushman M, et al. Validation of the Atherosclerotic Cardiovascular Disease Pooled Cohort Risk Equations. JAMA. 2014;():. doi: /jama RISK CALCULATOR VALIDATION Muntner P, Colantonio LD, Cushman M, et al. Validation of the Atherosclerotic Cardiovascular Disease Pooled Cohort Risk Equations. JAMA. 2014;():. doi: /jama THANK YOU! QUESTIONS? 18

19 GUIDELINES AVAILABLE AT: Stone NJ, Robinson J, Lichtenstein AH, et al ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;():. doi: /j.jacc Eckel RH, Jakicic JM, Ard JD, et al AHA/ACC Guideline on Lifestyle Management to Reduce Cardiovascular Risk: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;():. doi: /j.jacc OTHER REFERENCES Martinez T, Yavas D. Is the verdict finally in? Updates in cholesterol guidelines. ASHP Midyear Clinical Meeting. Orlando FL. 12 Dec Presentation. DiPiro JT. Pharmacotherapy: a pathophysiologic approach Print. Kavousi M, Leening MG, Nanchen D, et al. Comparison of Application of the ACC/AHA Guidelines, Adult Treatment Panel III Guidelines, and European Society of Cardiology Guidelines for Cardiovascular Disease Prevention in a European Cohort. JAMA. 2014;():. doi: /jama Muntner P, Colantonio LD, Cushman M, et al. Validation of the Atherosclerotic Cardiovascular Disease Pooled Cohort Risk Equations. JAMA. 2014;():. doi: /jama