Learning Objectives. Patient Case

Transcription

1 Joseph Saseen, Pharm.D., FASHP, FCCP, BCPS Professor and Vice Chair, Department of Clinical Pharmacy University of Colorado Anschutz Medical Campus Learning Objectives Identify the 4 patient populations in the new guideline recommendations for the treatment of patients with high blood cholesterol dyslipidemia that benefit from statin therapy and the rationale for treatment Review the ASCVD risk calculator and how it is used to determine need for statin therapy in primary prevention patients, including those with diabetes Describe high-intensity and moderate-intensity statin therapies and how to manage statin resistant patients Patient Case A 70-year-old woman has hypertension, CHD (chronic stable angina). Fasting lipid panel (FLP) 3 months ago was: Total cholesterol 190 mg/dl, HDL-C 40 mg/ dl, LDL-C 90 mg/dl, TG 300 mg/dl She was place on an aggressive lifestyle modifications at that time and has lost 10 lbs (current BMI is 28 kg/m 2 ). She is currently not on any lipid lowering drug therapy

2 Which of the following would you recommend for her today? 1. Check FLP, start a statin if LDL-C is >70 2. Start a moderate-intensity statin now 3. Start a moderate-intensity statin with extended-release niacin now 4. Start a moderate-intensity statin with fenofibrate now 5. Start a high-intensity statin now A 60-year-old African American man has type 2 diabetes. He is a primary prevention patient. 10-year risk of ASCVD is 6.5%. He is not on lipid lowering therapy and FLP is: total cholesterol 220 mg/dl, HDL-C 35 mg/dl, LDL-C 145 mg/dl, TG 200 mg/dl. Which of the following regimens is recommended by the ACC-AHA blood cholesterol guidelines for this patient? 1. Atorvastatin 20 mg daily 2. Rosuvastatin 10 mg daily 3. Pravastatin 40 mg daily 4. Simvastatin 40 mg daily 5. All of the above Risk Category High Risk: CHD or CHD Equivalent (10-y risk > 20%) Moderately High Risk: 2+ Risk Factors (10-y risk 10-20%) Moderate Risk: 2+ Risk Factors (10-y risk < 10%) Lower Risk: 0-1 Risk Factors (10-y risk < 10%) 2004: NCEP ATP III Goals * For Very High Risk patients LDL-C Goal (mg/dl) <100 Optional Goal: <70* <130 Optional Goal: <100 Non-HDL-C Goal (mg/dl) <130 <100 Initiate TLC (mg/dl) 100 < Consider Drug Treatment (mg/dl) 100 <100: for high risk patients : consider to achieve LDL-C goal of <100 <130 < <160 < : LDL-C Lowering Drugs Optional NCEP ATP III =National Cholesterol Education Program. Adult Treatment Panel III guidelines. TLC= Therapeutic Lifestyle changes Grundy S, et al. Circulation. 2004;110:

3 Clinical Practice Guidelines for Prevention (November 12, 2013) ACC/AHA Guidelines Preamble Guidelines attempt to define practices that meet the needs of patients in most circumstances and are not a replacement for clinical judgment. The ultimate decision about care of a particular patient must be made by the healthcare provider and patient in light of the circumstances presented by that patient. As a result, situations might arise in which deviations from these guidelines may be appropriate. What is new in the 2013 ACC/AHA Blood Cholesterol Guideline? The panel makes no recommendations for or against specific LDL-C or non-hdl-c targets for primary or secondary prevention of ASCVD

4 What is new in the 2013 ACC/AHA Blood Cholesterol Guideline? Focus on Atherosclerotic Cardiovascular Disease (ASCVD) reduction 4 Statin Benefit Groups New global risk assessment calculator for primary prevention patients Safety recommendations Role of biomarkers and noninvasive tests Planned further updates to cholesterol guideline ASCVD Statin Benefit Groups Heart healthy lifestyle habits are the foundation of ASCVD prevention. In individuals not receiving cholesterol-lowering drug therapy, recalculate estimated 10-y ASCVD risk every 4-6 y in individuals aged y without clinical ASCVD or diabetes and with LDL C mg/dl. Adults age >21 y and a candidate for statin therapy Clinical ASCVD No Age 75 y High-intensity statin (Moderate-intensity statin if not candidate for high-intensity statin) Age >75 y OR if not candidate for high-intensity statin Moderate-intensity statin Definitions of High- and Moderate-Intensity Statin Therapy High Moderate Daily dose lowers Daily dose lowers LDL-C by approx. LDL-C by approx. 50% 30% to <50% LDL-C 190 mg/dl No Diabetes Type 1 or 2 Age y No High-intensity statin (Moderate-intensity statin if not candidate for high-intensity statin) Moderate-intensity statin Estimated 10-y ASCVD risk 7.5%* High-intensity statin Estimate 10-y ASCVD Risk with Pooled Cohort Equations* 7.5% estimated 10-y ASCVD risk and age y Moderate-to-High Intensity Statin No ASCVD prevention benefit of statin therapy may be less clear in other groups In selected individuals, consider additional factors influencing ASCVD risk and potential ASCVD risk benefits and adverse effects, drug-drug interactions, and patient preferences for statin treatment 4 Statin Benefit Groups Clinical ASCVD LDL-C 190 mg/dl Diabetes Type 1 or 2 Age y 7.5% estimated 10-y ASCVD risk and age y

5 Clinical Atherosclerotic Cardiovascular Disease (ASCVD) Coronary heart disease (CHD) Acute Coronary Syndromes History of myocardial infarction Stable or unstable angina Coronary revascularization Symptomatic carotid artery disease Stroke TIA presumed to be of atherosclerotic origin Peripheral arterial disease or revascularization ASCVD Class I Recommendations High-Intensity statin therapy should be initiated or continued as first line therapy in men and women for < 75 years of age who have clinical ASCVD, unless contraindicated In individuals with clinical ASCVD in whom high- Intensity statin therapy would otherwise be used, when high-intensity statin therapy is contraindicated or when characteristics predisposing to statin-associated adverse effects are present, moderate-intensity statin should be used as the second option if tolerated A A Treating to New Targets (TNT): Study Design 10,001 patients with clinically evident CHD and LDL-C <130 mg/dl while taking atorvastatin 10 mg daily Double-blind trial, patients randomized to atorvastatin 80 mg or 10 mg over 5 years Primary end point: Time to first major CV event (CHD death, nonprocedural myocardial infarction, resuscitation after cardiac arrest, or stroke) LaRosa JC, et al. N Engl J Med. 2005;352:

6 Treating to New Targets (TNT): LDL-C Results and Primary Endpoint P<0.001 Atorvastatin 10 mg Atorvastatin 80 mg 22% Relative Risk Reduction P< Mean LDL-C Value (mg/ dl) Patients with Major CV Event (%) LaRosa JC, et al. N Engl J Med. 2005;352: ASCVD Class IIa Recommendation In individuals with clinical ASCVD > 75 years of age, it is reasonable to evaluate the potential for ASCVD riskreduction benefit and for adverse effects, DDIs, and to consider patient preferences, when initiating a moderate to high-intensity statin. It is reasonable to continue statin therapy in those who are tolerating it B Statin Intensity High-Intensity Moderate-Intensity Low-Intensity Daily dose lowers LDL C on average, by ~ 50% Atorvastatin (40) 80 mg Rosuvastatin 20 (40) mg Daily dose lowers LDL C on average, by ~ 30 to <50% Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin mg Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2 4 mg Daily dose lowers LDL C on average, by <30% Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg Specific statins and doses are noted in bold that were evaluated in randomized controlled trials. Statins and doses that are approved by the U.S. FDA but were not tested in the RCTs reviewed are listed in italics.

7 4 Statin Benefit Groups Clinical ASCVD LDL-C 190 mg/dl Diabetes Type 1 or 2 Age y 7.5% estimated 10-y ASCVD risk and age y LDL-C 190 mg/dl Class I Recommendations Adults 21 years of age with primary LDL C 190 mg/dl should be treated with statin therapy (10-year ASCVD risk estimation is not required): Use high-intensity statin therapy unless contraindicated. For individuals unable to tolerate high-intensity statin therapy, use the maximum tolerated statin intensity B LDL-C 190 mg/dl Class IIa Recommendation For individuals 21 years of age with an untreated primary LDL C 190 mg/dl, it is reasonable to intensify statin therapy to achieve at least a 50% LDL C reduction. Class IIb Recommendation For individuals 21 years of age with an untreated primary LDL C 190 mg/dl, after the maximum intensity of statin therapy has been achieved, addition of a nonstatin drug may be considered to further lower LDL C. Evaluate the potential for ASCVD risk reduction benefits, adverse effects, drug-drug interactions, and consider patient preferences. B C

8 National Lipid Association: Familial Hypercholesterolemia Familial hypercholesterolemias (FH) are genetic defects resulting in severe cholesterol elevations and increased risk of premature CHD Prevalence of FH is 1 in 300 to 500 Homozygous FH affects 1 in 1,000,000 Aggressive lipid lowering is necessary Target LDL-C reduction of at least 50% Greater LDL-C reductions may be necessary for FH patients with other CHD risk factors Journal of Clinical Lipidology 2011;5: Statin Benefit Groups Clinical ASCVD LDL-C 190 mg/dl Diabetes Type 1 or 2 Age y 7.5% estimated 10-y ASCVD risk and age y Primary Prevention in DM and LDL-C mg/dl Class I Recommendation Moderate-Intensity statin therapy should be initiated or continued for adults 40 to 75 years of age with DM A Class IIa Recommendation High-Intensity statin therapy is reasonable for adults age 40 to 75 years of age with DM with a 10 year ASCVD risk > 7.5% unless contraindicated In adults with DM less than 40 or > 75 years of age it is reasonable to evaluate for the potential ASCVD benefits and for adverse effects, DDIs, and to consider patient preference when deciding to initiate, continue, or intensify statin therapy B C

9 2013 ACC/AHA Guideline on the Assessment of Cardiovascular Risk Based on the Pooled Cohort Equations Predicts 10-year risk (and lifetime risk) of: Nonfatal/Fatal Myocardial Infarction Nonfatal/Fatal Stroke Information required: Age, sex, race, total cholesterol, HDL-C, systolic blood pressure, blood pressure lowering medication use, diabetes status, smoking status 48-year-old African American man with type 2 diabetes. Nonsmoker. BP is 136/86 mm Hg on antihypertensive drug therapy. TC = 200 mg/dl, HDL-C = 45 mg/dl, not on a statin. 10- Year and LifeFme ASCVD Risks Predicted Risk (%) Your 10- Year ASCVD 10- Year ASCVD Risk Risk (%) (%) for Someone Your Age with OpFmal Risk Factor Levels (shown above in column E) Your LifeFme ASCVD LifeFme ASCVD Risk Risk* (%) (%) for Someone at Age 50 with OpFmal Risk Factor Levels (shown above in column E) 4 Statin Benefit Groups Clinical ASCVD LDL-C 190 mg/dl Diabetes Type 1 or 2 Age y 7.5% estimated 10-y ASCVD risk and age y

10 Primary Prevention no DM and LDL-C mg/dl Class I Recommendations The pooled cohort equations should be used to estimate 10 year ASCVD risk for individuals with and LDL-C between 70 to 189 mg/dl without clinical ASCVD to guide initiation of statin therapy for primary prevention Adults age 40 to 75 years of age without clinical ASCVD or DM and a 10 yr ASCVD risk > 7.5% should be treated with a moderate to high intensity statin therapy B A Class IIa Recommendations Reasonable to offer moderate intensity statin to adults 40 to 75 years of age with LDL-C mg/dl, without clinical ASCVD or DM and a 10 year ASCVD risk of 5 to < 7.5% B Primary Prevention no DM and LDL-C mg/dl Class IIb Recommendations In adults with LDL C <190 mg/dl who are not otherwise identified in a statin benefit group, or for whom after quantitative risk assessment a risk-based treatment decision is uncertain, additional factors may be considered to inform treatment decision making. In these individuals, statin therapy for primary prevention may be considered after evaluating the potential for ASCVD risk reduction benefits, adverse effects, drug-drug interactions, and discussion of patient preferences. Additional Risk Factors: LDL-C > 160 mg/dl or genetic hyperlipidemia; Family hx ASCVD in father < 55 yrs of age or mother < 65 years of age; hscrp > 2 mg/dl, CAC score > 300 Agatston units or > 75 percentile for age, sex, and ethnicity; ABI < 0.9; or lifetime risk of ASCVD C Lipid-Lowering Therapies Statins (atorvastatin, fluvastatin, lovastatin, pravastatin, pitavastatin, rosuvastatin, simvastatin) Bile acid sequestrants (colesevelam, cholestyramine, colestipol) LDL-C HDL-C TG 18-63% 5-15% 7-30% 15-30% 3-5% 0 or Nicotinic acid 5-25% 15-35% 20-50% Fibric acid derivatives (gemfibrozil, fenofibrate) Cholesterol absorption inhibitor (ezetimibe) Omega-3 fatty acids (Rx strength) 5-20% or 10-20% 20-50% 18% 1% 7%? 9% 45% Executive summary of NCEP ATP III. JAMA. 2001; 285: ; Crestor package insert. Astra-Zeneca, 2009; Zetia package insert. Merck/Schering-Plough Pharmaceuticals, 2009; Lovaza package insert. GlaxoSmithKline, 2009; Livalo package insert. Kowa Pharmaceuticals America, 2010.

11 Anticipated Assess medication and lifestyle adherence Fasting lipid panel therapeutic response? No Indicators of anticipated therapeutic response and adherence to selected statin intensity: High-intensity statin therapy reduces LDL C approx. 50% from the untreated baseline Moderate-intensity statin therapy reduces LDL C approx. 30% to <50% from the untreated baseline. Reinforce continued adherence Follow-up 3-12 mo Less-than-anticipated therapeutic response Anticipated therapeutic response? Intolerance to recommended dose of statin therapy Management of statin intolerance No Reinforce improved adherence Increase statin intensity OR Consider addition of nonstatin drug therapy No Reinforce medication adherence Reinforce adherence to intensive lifestyle changes Exclude secondary causes of hypercholesterolemia Follow-up 4-12 wk & thereafter as indicated Follow-up 4-12 wk Safety Recommendations Use moderate-intensity statin therapy in individuals whom high-intensity therapy is recommended, but characteristics predisposing them to statin associated adverse effects are present Multiple or serious comorbidities Previous statin intolerance or muscle disorders Unexplained ALT elevations >3 times ULN Patient characteristics or concomitant use of drugs affecting statin metabolism >75 years of age Statin Safety Recommendations Mild-moderate muscle symptoms during statin therapy: Discontinue the statin until the symptoms can be evaluated. Evaluate other conditions that might increase risk for muscle symptoms If muscle symptoms resolve, and no contraindication exists, give the original or lower dose of the same statin. If symptoms recur, discontinue the statin. Once symptoms resolve, use low dose of a different statin. Once low dose statin is tolerated, increase as tolerated. If, after 2 months without statin treatment, muscle symptoms or elevated CK levels do not resolve, consider other causes. If persistent muscle symptoms are from a condition unrelated to statin therapy, or if the predisposing condition has been treated, resume statin therapy at the original dose.

12 Treatment Strategies in Patients with Statin Intolerance The Cleveland Clinic experience Retrospective analysis of 1,605 patients referred for statin intolerance 72.5% were able to tolerate a statin Intermittent statin dosing (n=149) had lower LDL- C reduction compared with daily dosing (n=1014): 21.3 vs 27.7% (P<0.04) Trend toward a decrease in all-cause mortality at 8 years for patients on daily/intermittent statin dosing compared with those who discontinued statin (P=0.08) Am Heart J 2013;166: Statin Safety Recommendations Individuals receiving statin therapy should be evaluated for new-onset diabetes mellitus and those who develop diabetes mellitus during statin therapy should engage in CV risk reduction lifestyle modifications and continue statin therapy to reduce their risk of ASCVD Nonstatin Drugs The panel could find no data supporting the routine use of nonstatin drugs combined with statin therapy to reduce further ASCVD events In individuals who are candidates for statin treatment but are completely statin intolerant, it is reasonable to use nonstatin cholesterollowering drugs that have been shown to reduce ASCVD events in RCTs if the ASCVD riskreduction benefits outweigh the potential for adverse effects.

13 Parting Thoughts. 4 evidence based statin benefit groups Statin intensity is clinically important High-priority research areas to evaluate evidence gaps: Primary prevention in patients > 75 years Goals vs fixed-dose statin therapy Low-intensity statin plus nonstatin in statinintolerant patients New onset diabetes with statin therpay Role of new and emerging drug therapies Patient Case A 70-year-old woman has hypertension, CHD (chronic stable angina). Fasting lipid panel (FLP) 3 months ago was: Total cholesterol 190 mg/dl, HDL-C 40 mg/ dl, LDL-C 90 mg/dl, TG 300 mg/dl She was place on an aggressive lifestyle modifications at that time and has lost 10 lbs (current BMI is 28 kg/m 2 ). She is currently not on any lipid lowering drug therapy Which of the following would you recommend for her today? 1. Check FLP, start a statin if LDL-C is >70 2. Start a moderate-intensity statin now 3. Start a moderate-intensity statin with extended-release niacin now 4. Start a moderate-intensity statin with fenofibrate now 5. Start a high-intensity statin now

14 A 60-year-old African American man has type 2 diabetes. He is a primary prevention patient. 10-year risk of ASCVD is 6.5%. He is not on lipid lowering therapy and FLP is: total cholesterol 220 mg/dl, HDL-C 35 mg/dl, LDL-C 145 mg/dl, TG 200 mg/dl. Which of the following regimens is recommended by the ACC-AHA blood cholesterol guidelines for this patient? 1. Atorvastatin 20 mg daily 2. Rosuvastatin 10 mg daily 3. Pravastatin 40 mg daily 4. Simvastatin 40 mg daily 5. All of the above Challenges with Lipid Management "Drugs don't work in patients who don't take them." Former U.S. surgeon general C. Everett Koop