Dyslipidemia 2016


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Dyslipidemia 2016

  1. 1. Updates in themanagement of dyslipidemia 2016
  2. 2. 2
  3. 3. 3
  4. 4. 2013 ACC/AHA
  5. 5. Prescribe statin up to the highest recommended dose, or highest tolerable dose to reach the target level
  6. 6. Risk Levels  Very High Risk:  A calculated SCORE ≥10%  Documented CVD by invasive or non-invasive testing  Type 2 diabetes, type 1 diabetes with target organ damage  Moderate to severe CKD ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2011 Jul;32(14):1769-818.
  7. 7. Risk Levels  High Risk:  A calculated SCORE ≥5 to <10%  Markedly elevated single risk factors  Moderate Risk:  A calculated SCORE ≥1 to <5%  Low Risk:  A calculated SCORE <1% ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2011 Jul;32(14):1769-818.
  8. 8. VERY HIGH RISK: LDL-C< 1.8 mmol/L (<70mg%) and/or ≥ 50% LDL –C reduction(IA) HIGH RISK: LDL-C< 2.5 mmol/L (<100mg%) (IIa A) MODERATE RISK:LDL-C< 3 mmol/L (<115mg%) (IIa C) Recommendations for treatment targets for LDL-C
  9. 9. 3. M. Bucci, A. Mezzetti, per conto della SISA sezione Abruzzo 1. Grundy SM et al. Circulation 2004; 110:227-239 2. Smith S. et al. J.Am. Coll. Cardiol. 2006; 2130-2139 Baseline LDL-C LDL-C reduction to reach target > 200 > 50% 180-200 45-50% 160-180 40-45% 140-160 30-40% 120-140 20-30% TARGET LDL-C < 100 (2.6)
  10. 10. Baseline LDL-C LDL-C reduction to reach target > 200 > 50% 180-200 > 50% 160-180 > 50% 140-160 > 50% 120-140 40-50% 3. M. Bucci, A. Mezzetti, per conto della SISA sezione Abruzzo 1. Grundy SM et al. Circulation 2004; 110:227-239 2. Smith S. et al. J.Am. Coll. Cardiol. 2006; 2130-2139 TARGET LDL-C < 70 (1.8)
  11. 11. ROSUVA 20 mg ROSUVA 40 mg Average LDL-C Reduction from baseline (%) -20 -25 -30 -35 -40 -45 -50 -55 -60 ROSUVA 10 mg ATORVA 20 mg ATORVA 40 mg ATORVA 80 mg ATORVA 10 mg SIMVA 20 mg SIMVA 40 mg SIMVA 10 mg FLUVA 80 mg PRAVA 40 mg Adapted from Jones PH et al. Am J Cardiol 2003;92:152–160 Statin ?
  12. 12. • If non-HDL-C is used, the targets should be; <2.6 mmol/L (<~100 mg/dL) in those at VERY HIGH CV risk and <3.3 mmol/L (<~130 mg/dL) in those at HIGH CV risk (class IIa B) • If apo B is available, the targets are; <80 mg/dL in those at VERY HIGH CV risk and <100 mg/dL in those at HIGH CV risk (class IIa B) ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2011 Jul;32(14):1769-818. Treatment Targets Other Than LDL-C
  13. 13. Moderate to Severe Chronic Kidney Disease  Statins→beneficial effect on pathological proteinuria (>300 mg/day); considered in stage 2-4 CKD patients (class IIa B)  Statins (as monotherapy or in combination with other drugs)→considered to achieve LDL-C <1.8 mmol/L (<~70 mg/dL)(class IIa C) ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2011 Jul;32(14):1769-818.
  14. 14. Familial Hypercholesterolaemia  FH is suspected in subjects with  CVD aged <50 years (♂) or <60 years (♀),  relatives with premature CVD,  known FH in the family.  Confirm the diagnosis with clinical criteria or with DNA analysis.  Family screening is indicated when a patient with HeFH is diagnosed. ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2011 Jul;32(14):1769-818.
  15. 15. If TG are 200–499 mg/dL, non-HDL-C should be <130 mg/dL Lipid Management in high TG: Recommendation l lla llb lll B l lla llb lll B Further reduction of non-HDL-C to <100 mg/dL is reasonable Therapeutic options to reduce non-HDL-C: More intense LDL-C–lowering therapy I (B) or Niacin (after LDL-C–lowering therapy) IIa (B) or Fibrate (after LDL-C–lowering therapy) IIa (B) l lla llb lll C If TG are >500 mg/dL, therapeutic options to prevent pancreatitis are fibrate or niacin before LDL lowering therapy; and treat LDL-C to goal after TG-lowering therapy, Achieve non-HDL-C <130 mg/dL, if possible TG=Triglycerides; HDL-C=high-density lipoprotein cholesterol Smith SC Jr et al. Circulation 2006;113:2363–2372.
  16. 16. Management of Lipids in Adults with Diabetes Mellitus Goal Borderline risk High risk Treatment decisions based on LDL cholesterol levels in adults with diabetes mellitus Patients without: • Cardiovascular Heart Disease (CHD) • Peripheral Vascular Disease (PVD) • Cerebrovascular Disease (CVD) LDL < 100 At Goal (recheck yearly) Initiate Lifestyle intervention, including Medical Nutrition Therapy (MNT) and Drug Therapy At Goal (recheck yearly) LDL 100-129 LDL  130 Yes No Yes No Initiate Lifestyle Intervention, MNT & Drug Therapy Initiate MNT Treatment options for diabetic patients without CHD, PVD, or CVD with LDL 100-129 mg/dl Initiate/intensify lifestyle and/or drug therapies specifically to lower LDL for 3-6 months Emphasize weight reduction and increase physical activity in persons with the metabolic syndrome Recheck LDL in 3-6 months; if not at goal, consider drug treatment with a statin Patients with: • Cardiovascular Heart Disease (CHD) • Peripheral Vascular Disease (PVD) • Cerebrovascular Disease (CVD) Or Adapted from: Diabetes Care, vol. 36, Supplement 1, January 2013 *ADA 2013 Update: In people with diabetes over the age of 40 without CVD who have one or more other CVD risk factors, statin therapy to achieve LDL reduction of approximately 30% may be appropriate, regardless of baseline levels. LDL < 70 is an option Statin Therapy is contraindicated in pregnancy LDL cholesterol < 100 mg/dl 100-129 mg/dl *  130 mg/dl HDL cholesterol > 40 mg/dl (men) > 50 mg/dl (women) 35-45 mg/dl < 35 mg/dl Triglycerides < 150 mg/dl 200-399 mg/dl  400 mg/dl Non-HDL cholesterol (Total Chol – HDL) treatment goal = 30 mg/dl above LDL treatment target. In the absence of severe hypertriglyceridemia (>1,000 mg/dl), therapy targeting low HDL and/or elevated triglycerides lacks the strong evidence base of statin therapy to lower LDL cholesterol.
  17. 17. Reduction in Total (First and Recurrent) Cardiovascular Events with Ezetimibe/Simvastatin compared with Simvastatin Alone post ACS in the IMPROVE-IT Trial Sabina A. Murphy, Christopher Cannon, Robert Giugliano, Michael Blazing, Thomas Musliner, Andrew Tershakovec, Jennifer White, Kelly Im, Naveen Deenadayalu, Haral Darius, Witold Ruzyllo, Andrew Tonkin, Uma Kher, Robert Califf, Eugene Braunwald On behalf of the IMPROVE IT Investigators
  18. 18. Patients stabilized post ACS ≤ 10 days: LDL-C 50–125*mg/dL (or 50–100**mg/dL if prior lipid-lowering Rx) Standard Medical & Interventional Therapy Ezetimibe / Simvastatin 10 / 40 mg Simvastatin 40 mg Duration: Minimum 2 ½-year follow-up (5314 events) Primary Endpoint: CV death, MI, hospital admission for UA, coronary revascularization (≥ 30 days after randomization), or stroke N=18,144 Study Design Cannon CP AHJ 2008;156:826-32; Califf RM NEJM 2009;361:712-7; Blazing MA AHJ 2014;168:205-12
  19. 19. The Statin Decade: For LDL: “Lower is Better” 0 5 10 15 20 25 30 R² = 0.9029 p < 0.0001 LDL Cholesterol (mg/dl) CHDEvents(%) Adapted and Updated from O’Keefe, J. et al., J Am Coll Cardiol 2004;43:2142-6. 30 50 70 90 110 130 150 170 190 210 4S CARE LIPID HPS PROVE IT –TIMI 22 IMPROVE IT66 52 TNT
  20. 20. Downloaded from www.ezetrol.ae Ezetimibe Coadministered with Atorvastatin in Patients with Hypercholesterolemia and Coronary Heart Disease Results of Two Randomized, Double-Blind, Placebo- Controlled Trials
  21. 21. Downloaded from www.ezetrol.ae Summary and Conclusions • Ezetimibe coadministered with atorvastatin 10 or 20 mg was significantly* more effective than atorvastatin in CHD patients  More patients achieved LDL-C goal (≤2.60 mmol/L)  Greater reduction in LDL-C  Improved lipid profile—TC, TG, HDL-C,** cholesterol ratios • Ezetimibe coadministered with atorvastatin was well tolerated  Similar to atorvastatin alone • Treating two sources (production and absorption) of cholesterol ensured more patients achieve their lipid lowering goals *p≤0.001; **p=0.021
  22. 22. Reference Age Risk Factors Statin Intensity* <40 years None None ASCVD risk factor(s)** Moderate or high ASCVD High 40–75 years None Moderate ASCVD risk factors High ACS & LDL >50 who can’t tolerate high dose statin Moderate + ezetimibe >75 years None Moderate ASCVD risk factors Moderate or high ASCVD High ACS & LDL >50 who can’t tolerate high dose statin Moderate + ezetimibe Recommendations for Statin Treatment in People with Diabetes * In addition to lifestyle therapy. ** ASCVD risk factors include LDL cholesterol ≥100 mg/dL (2.6 mmol/L), high blood pressure, smoking, overweight and obesity, and family history of premature ASCVD. American Diabetes Association Standards of Medical Care in Diabetes. Cardiovascular disease and risk management. Diabetes Care 2016; 39 (Suppl. 1): S60-S71
  23. 23. Reference ● Combination therapy (statin/fibrate) doesn’t improve ASCVD outcomes and is generally not recommended A. Consider therapy with statin and fenofibrate for men with both trigs ≥204 mg/dL (2.3 mmol/L) and HDL ≤34 mg/dL (0.9 mmol/L). B ● Combination therapy (statin/niacin) hasn’t demonstrated additional CV benefit over statins alone, may raise risk of stroke & is not generally recommended. A ● Statin therapy is contraindicated in pregnancy. B Recommendations: Lipid Management American Diabetes Association Standards of Medical Care in Diabetes. Cardiovascular disease and risk management. Diabetes Care 2016; 39 (Suppl. 1): S60-S71
  24. 24. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults ATP IV
  25. 25. Summary of Statin Initiation Recommendations to Reduce ASCVD Risk
  26. 26. Summary of Statin Initiation Recommendations to Reduce ASCVD Risk
  27. 27. Age ≥21 years
  28. 28. Age ≥21 years
  29. 29. Clinical ASCVD: Initiating Statin Therapy *Fasting lipid panel preferred. In a nonfasting individual, a nonfasting non-HDL–C ≥220 mg/dL may indicate genetic hypercholesterolemia that requires further evaluation or a secondary etiology. If nonfasting triglycerides are ≥500 mg/dL, a fasting lipid panel is required. †It is reasonable to evaluate the potential for ASCVD benefits and for adverse effects, and to consider patient preferences, in initiating or continuing a moderate- or high- intensity statin, in individuals with ASCVD >75 years of age.
  30. 30. Intensity of Statin Therapy *Individual responses to statin therapy varied in the RCTs and should be expected to vary in clinical practice. There might be a biologic basis for a less-than-average response. †Evidence from 1 RCT only: down-titration if unable to tolerate atorvastatin 80 mg in IDEAL (Pedersen et al). ‡Although simvastatin 80 mg was evaluated in RCTs, initiation of simvastatin 80 mg or titration to 80 mg is not recommended by the FDA due to the increased risk of myopathy, including rhabdomyolysis.
  31. 31. What about individuals of “intermediate risk” (<7.5% ASCVD risk)? • Optional additional risk measurement tools to refine predicted risk – Family history of premature ASCVD? – High-sensitivity CRP – Coronary artery calcium – Ankle brachial Indices (ABI)
  32. 32. Individuals Not in a Statin Benefit Group • In those for whom a risk decision is uncertain, these factors may inform clinical decision making: • Family history of premature ASCVD • Elevated lifetime risk of ASCVD • LDL-C ≥160 mg/dL • hs-CRP ≥2.0 mg/L • CAC score ≥300 Agaston units • ABI <0.9 • Statin use still requires discussion between clinician and patient
  33. 33. Is the Patient at High Risk of ASCVD? High-risk defined as ≥1 of the following: • Clinically established coronary heart disease • Cerebrovascular disease • Peripheral arterial disease • Abdominal aortic aneurysm • Diabetes mellitus • Chronic kidney disease • 10-year predicted ASCVD risk ≥7.5% by Pooled Cohort Equation
  34. 34. Yes: Patient is at High-Risk of ASCVD Implement treatment recommendations: • A – Aspirin / Antiplatelet therapy • B – Blood pressure control • C – Cholesterol control /Cigarette smoking cessation • D – Diet and weight management / Diabetes and blood sugar control • E – Exercise
  35. 35. Yes: Patient is at Intermediate Risk of ASCVD Consider additional testing to further assess risk: • CT scan for coronary artery calcium (CAC) score • Measure high-sensitivity C-reactive protein (hsCRP) Do additional tests indicate that patient may benefit from treatment because they are really at higher risk?
  36. 36. Evolution of NCEP ATP III to ACC/AHA- ATPIV III 2013 Guideline NCEP ATP III AHA/ACC Year introduced 2001 (updated in 2004) 2013 Focus • Reducing risk of coronary heart disease (CHD) • Reducing risk of atherosclerotic CV disease (ASCVD), which includes CHD events as well as stroke/TIA, peripheral arterial disease or revascularization Risk Assessment • Risk categories / major risk factors that modify LDL-C goals • Framingham 10-year Risk Score (CHD death + nonfatal MI) • Pooled Cohort Equations (Fatal and nonfatal CHD + fatal and nonfatal stroke) Risk Categories • 3 main risk categories : CHD or CHD risk equivalent, 2+ risk factors with 10-yr CHD risk ≤20%, 0-1 risk factor + 10-yr risk <10% • CHD risk equivalent: diabetes, clinical CHD, symptomatic carotid artery disease, peripheral artery disease • 4 statin benefit groups: Clinical ASCVD, Primary elevations of LDL–C ≥190 mg/dL (≥4.9 mmol/L), Diabetes without clinical ASCVD, No diabetes or CVD with 10-year ASCVD risk ≥7.5% Treatment Targets • LDL-C = primary target • CHD or CHD risk equivalents: <100 mg/dL (<2.6 mmol/L) (option < 70 mg/dL [<1.8 mmol/L] in very high risk patients) • 2+ risk factors with 10-yr CHD risk ≤20%: <130 mg/dL (<3.4 mmol/L) (Option <100 mg/dL [<2.6 mmol/L] if 10-20% risk), 0-1 risk factor + 10-yr risk <10%: <160 mg/dL (<4.1 mmol/L) • Intensity of statin therapy • High intensity statin therapy (LDL-C reduction >50%) recommended for most patients in 4 statin benefit groups: • Atorvastatin 40 or 80 mg • Rosuvastatin 20-40 mg Treatment Recommendati ons • Statin (or bile acid sequestrant or nicotinic acid) to achieve LDL-C goal • Maximally tolerated statin first-line to reduce risk of ASCVD events
  37. 37. Statin Treatment: Heart Failure and Hemodialysis The Expert Panel makes no recommendations regarding the initiation or discontinuation of statins in patients with NYHA class II–IV ischemic systolic heart failure or in patients on maintenance hemodialysis. No recommendation
  38. 38. Nonstatin Safety: Fibrates Renal status should be evaluated before fenofibrate initiation, within 3 months after initiation, and every 6 months thereafter. Assess renal safety with both a serum creatinine level and an eGFR based on creatinine.
  39. 39. Nonstatin Safety: Fibrates (cont.) Harm  Fenofibrate should not be used if moderate or severe renal impairment, defined as eGFR <30 mL/min per 1.73 m2, is present.  If eGFR is between 30 and 59 mL/min per 1.73 m2, the dose of fenofibrate should not exceed 54 mg/day*.  If, during follow-up, the eGFR decreases persistently to ≤30 mL/min per 1.73 m2, fenofibrate should be discontinued. *Consult the manufacturer's prescribing information as there are several forms of fenofibrate available.
  40. 40. Take Home Message 1. Rather than LDL–C or non-HDL– C targets, new guideline uses the intensity of statin therapy as the goal of treatment. 2. Know the 4 Statin Benefit Groups: I. Individuals with clinical ASCVD II. Individuals with primary elevations of LDL–C ≥190 mg/dL III. Individuals 40 to 75 years of age with diabetes and LDL–C 70 to189 mg/dL without clinical ASCVD IV. Individuals without clinical ASCVD or diabetes who are 40 to 75 years of age with LDL–C 70 to 189 mg/dL and have an estimated 10-year ASCVD risk of 7.5% or higher. (using the Pooled Cohort Equations for ASCVD risk prediction)
  41. 41. Goals LDL-C Non–HDL-C Apo B Highest-Risk Patients <70 mg/dL <100 mg/dL <80 mg/dL • Known cardiovascular disease (CVD) • Diabetes plus ≥1 additional major CVD risk factor High-Risk Patients <100 mg/dL <130 mg/dL <90 mg/dL • No diabetes or known CVD but ≥2 major CVD risk factors • Diabetes but no other major CVD risk factors “In individuals on statin therapy who continue to have low HDL-C or elevated non–HDL-C, especially if Apo B levels remain elevated, combination therapy is recommended. The preferred agent to use in combination with a statin is nicotinic acid…” Reprinted from Brunzell JD, et al. J Am Coll Cardiol. 2008;51:1512–1524, with permission from Elsevier. Treatment Goals for Patients With Cardiometabolic Risk and Lipoprotein Abnormalities