Conflicts of interest. What's the Skinny on the Lipid Guidelines? Key Differences. Are you applying the new ACC/AHA Lipid guidelines in your practice?

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1 Conflicts of interest What's the Skinny on the Lipid Guidelines? The presenter has no relevant conflicts of interest to disclose. Kathleen Vest, PharmD, CDE, BCACP At the end of this presentation, pharmacist participants should be able to: Describe the major differences and controversies between current and previous guidelines Discuss the rationale for updated treatment strategies as compared to previous treatment goals Differentiate high and moderate- intensity statin therapy and indications for each Identify the 4 statin benefit groups as described in the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines At the end of this presentation, technician participants should be able to: Discuss atherosclerotic cardiovascular disease (ASCVD) and its associated risks for complications and death. Identify patient populations at risk for ASCVD Describe the medications used to reduce the risk of ASCVD. Are you applying the new ACC/AHA Lipid guidelines in your practice? A. Yes B. No C. A little bit, but I m still not completely comfortable. Key Differences No more LDL goals and non-hdl goals Statin benefit groups ASCVD 10-year risk estimation Safety recommendations References: Neil J. Stone, Jennifer Robinson, Alice H. Lichtenstein, 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. Circulation. published online November 12, ASCVD Risk Calculator 1

2 What is ASCVD? Atherosclerotic Cardiovascular Disease Coronary Artery Disease (CAD) or Coronary Heart Disease (CHD) History of cardiovascular events including: Myocardial infarction (MI) Angina Stroke or Transient ischemic attack (TIA) Acute Coronary Syndrome (ACS) Coronary vascularization Peripheral Arterial Disease (PAD) ASCVD Facts Leading cause of death and medical costs in the United States 1 in 3 Americans die of heart disease and stroke ASCVD can be prevented by: Healthy lifestyle: Regular physical activity, healthy diet, avoiding smoking, maintaining healthy weight Treatment of cholesterol and blood pressure (Adult Treatment Panel)- ATP III Guidelines 2001 Low density lipoprotein (LDL) goals based on CHD risk Framingham scoring tool to help determine 10 year CHD risk LDL goal <100 mg/dl for secondary prevention OR CHD risk equivalents (ex. Diabetes mellitus (DM) LDL goal <130 mg/dl for patients with > 2 following risk factors: HTN, age (male >45, female >55), active smoking, low HDL, premature family history (FH) of heart disease) LDL goal <160 mg/dl for patients with 0-1 of the above risk factors) Provided recommendations for patients with elevated triglycerides (TG) and low high-density cholesterol (HDL) JAMA 2001;285: ACC/AHA Guidelines (ATP-IV) American College of Cardiology (ACC) and American Heart Association (AHA) in collaboration with National Heart, Lung and Blood Institute (NHLBI) Focus on ASCVD Risk Reduction No more LDL goals ASCVD calculator Use of four risk groups to help guide treatment Emphasis on medications proven to lower ASCVD events Fixed statin doses (moderate, high intensity) Decreased focus on non-statins Circulation 2013 ACC/AHA Guidelines on Cholesterol (e-publication Similarities Both guidelines seek to lower the risk of cardiovascular events Both sets of guidelines emphasize a healthy lifestyle Avoidance of smoking Maintain healthy weight Physical activity Healthy Diet Dietary recommendations The 2013 ACC/AHA Lifestyle Management Guideline Dietary recommendations*: Low saturated fat Low trans fat Low sodium Eat more: Vegetables, fruits, whole grains, low fat dairy, poultry, fish, nuts, non tropical vegetable oils Patients should limit: sweets, sugar-sweetened beverages, red meats *Eckel RH, Jakicic JM, Ard JD, Miller NH, Hubbard VS, Nonas CA, et al ACC/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 (PMID: ). 2

3 Update on the Lipid Guidelines There is no randomized controlled trial (RCT) evidence to support LDL or non-hdl treatment targets. The RCTs identified in the panel s review of the evidence indicated a consistent reduction in ASCVD events with statin therapy in primary AND secondary prevention. Exception: NYHA Class II-IV heart failure and patients receiving hemodialysis Four groups that benefit from statin therapy Four Major Statin Benefit Groups Patients ( 21 years old) WITH clinical ASCVD Patients ( 21 years old) with LDL of 190 mg/dl Patients with Diabetes age with LDL mg/dl No clinical ASCVD or DM- age with LDL mg/dl and 10 year ASCVD risk >7.5 ASCVD 10-year risk calculator Provides 10 year ASCVD risk estimate for patients aged Tk Takes into account: Age, gender, Smoking status, HTN, BP, TC, HDL, DM, stroke, and race Also helpful to use apps if using a smart phone Patient Case #1 Dexter Morgan is a 40 year old Caucasian male who visits your clinic. PMH: + smoking, HTN (hypertension). Today, his BP is 148/92. Current medications: Lisinopril 10 mg daily Labs: TC 238, TG 298, HDL 39, LDL 142, A1c 8.9%, SCr 1.1. What is Mr. Morgan s ASCVD score? A. 2.5% B. 5.7% C. 11.1% D. 20% 3

4 Mr. Morgan should receive a statin. A. True B. False Intensity of statin therapy in primary and secondary prevention of ASCVD High Intensity Statin Therapy Daily dose lowers LDL C, on average, by approximately 50% Atorvastatin (40) 80 mg Rosuvastatin 20 (40) mg Moderate Intensity Statin Therapy Daily dose lowers LDL C, on average, by approximately 30% to <50% Atorvastatin mg Rosuvastatin 5 10 mg Simvastatin mg Pravastatin mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg BID Pitavastatin 2 4 mg Low Intensity Statin Therapy Daily dose lowers LDL C, on average, by <30% Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg Circulation 2013 ACC/AHA Guidelines on Cholesterol (e-publication). Statin Groups/Recommendations Patients ( 21 y/o) with clinical ASCVD: High Intensity Statin Patients ( 21 y/o) with LDL of 190 mg/dl: High Intensity Statin Patients with Diabetes age with LDL mg/dl 10 year ASCVD risk < 7.5%: Moderate Intensity Statin 10 year ASCVD risk 7.5%: High Intensity Statin No clinical ASCVD or DM- age with LDL mg/dl and 10 year ASCVD risk >7.5 Moderate-High Intensity Statin Circulation 2013 ACC/AHA Guidelines on Cholesterol (e-publication). Fi Case #2: Ms. Wolowitz Ms. Wolowitz is a 53 y/o Caucasian female with a PMH of Type 2 DM, obesity, and HTN. She does not smoke. She currently does not have prescription coverage. She takes losartan 25 mg daily, y,pravastatin 20 mg daily, Aspirin 81 mg daily, metformin 1000 mg twice daily BP today: 132/90 Lipid panel results: TC 198, TG 96, HDL 38, LDL 62 What is Mrs. Wolowitz s 10- year ASCVD score? A. 2.3% B. 5.0% C. 6.5% D. 9.7% 4

5 Your recommendation for Ms. Wolowitz? A. Continue present management B. Increase pravastatin to 40 mg daily C. Switch to rosuvastatin 10 mg daily D. Add ezetimibe 10 mg daily Non-Statin Therapy The panel states that non-statin therapies do not offer benefit at reducing ASCVD risk. (Examples: ezetimibe, fish oil, niacin, fibrates) Consider non-statin therapy if: Patient does not respond as expected to statin therapy Patient is unable to tolerate appropriate statin intensity Statin intolerance Safety of Statin Therapy Myalgias (0.5-5%) Rhabdomyolysis (0.002%) Contraindicated in pregnancy and in patients with active liver disease. Recent addition to statin labeling in 2012 Reversible memory loss, confusion Increased blood sugar and A1c- new onset DM The FDA states that the BENEFITS of statins outweighs the above risks. Laboratory Monitoring Baseline tests: A1c, LFTs, thyroid to rule out secondary causes of dyslipidemia Fasting Lipid panel Within 4-12 weeks after initiation or dose adjustment of drug therapy and every 3-12 months thereafter LFTs- at baseline and as clinically indicated thereafter The FDA revised labels in Feb 2012 to remove the need for periodic LFT monitoring Laboratory monitoring CK (Creatine Kinase) At baseline in patients at risk for myopathy. Repeat if symptoms of muscle pain How low is too low for LDL? The guidelines state that patients with LDL <40 mg/dl on two consecutive occasions should have statin dose reduced. Limited evidence on this topic Many statin drug-drug interactions Statins are metabolized by CYP450 system Atorvastatin, lovastatin, and simvastatin 3A4 Strong 3A4 inhibitors increased statin ADRs Erythromycin, Clarithromycin, Protease inhibitors, Azole antifungals, verapamil, diltiazem, amiodarone FDA Simvastatin dosing limitations Decreased statin effectiveness with inducers (rifampin, carbamazepine, phenytoin) fluvastatin 2C9 rosuvastatin 2C9/2C19 pravastatin and pitavastatin minimal hepatic metabolism Avoid gemfibrozil in combination with statins Separate administration of colesevelam, cholestyramine by 4 hours 5

6 Other clinical recommendations Consider moderate-intensity doses for patients who would qualify for high-intensity but have certain characteristics that predispose them to side effects > 75 years old Multiple or serious comorbidities, including impaired renal or hepatic impairment History of previous statin intolerance or muscle disorders Unexplained ALT elevations > 3x ULN Concomitant drugs that affect statin metabolism Use the maximally tolerated intensity of statin for patients unable to tolerate the recommended intensity Case #3 Carl Fredricksen is a 73 year old male with a history of CAD (CABG in 2010), Type 2 DM, and HTN He presents to your pharmacy with a prescription for atorvastatin 40 mg daily. He tells you he is afraid to take statins because he one time got muscle pain while on simvastatin. He asks you about your opinion. Ann Intern Med. 2014;160: Should Mr. Fredricksen start taking the atorvastatin? A. Yes, because he has ASCVD B. Yes, because of his ASCVD 10-year risk ik C. No, because of his history of myalgias on statin therapy D. No, because he warrants moderate intensity statin therapy Managing statin complaints Mr. Fredricksen returns to the pharmacy 4 weeks after starting his prescription for atorvastatin. He is complaining of muscle pain- mainly in the upper thigh. Next steps? Have a discussion regarding the patient s symptoms, history, and timeline Refer this patient to his physician for further evaluation Managing myalgias D/c statin temporarily Consider checking CK level- especially if severe pain R l h bl Rule out other possible causes Renal or hepatic impairment, musculoskeletal/ rheumatologic conditions, vitamin D deficiency Can re-challenge with either the same statin, or an alternative statin at same or lower intensity 6

7 Some evidence gaps and limitations of ATP-IV Expert panel was not able to find evidence for statin benefit for Class II-IV heart failure or receiving hemodialysis 10 year ASCVD Risk estimation limitations: Calculator only for age May overestimate risk in some patients Risk estimation requires TC range of mg/dl Does not take into account family history Still unclear evidence regarding combination therapy Risk of new-onset diabetes with statin therapy? LDL <100 as a quality measure- will this change? Are the ATP4 being embraced? Pros Somewhat of a simplified approach More evidence-based approach Less monitoring? Clear guidance for medication recommendations Cons Many clinicians are still comfortable with LDL goals Patient concerns: Why do I need medicinemy cholesterol has always been low? When they increased my statin- my muscles hurt Estimated 10-year ASCVD risk calculator has not been evaluated Controversy in the Media Message from AHA CEO regarding myths surrounding ATP-IV Lifestyle choices no longer matter False! A healthy lifestyle remains the foundation of preventing ASCVD These guidelines may lead to unnecessary prescribing of statins False! Goal is to have a more individualized approach Statins cause more harm than good False! Statins are considered safe medications overall. Benefits outweigh the risks in most patients These guidelines were influenced by the pharmaceutical industry. False! The ACC/AHA expert panel had a strict disclosure policy. Also, many statins are available as low-cost generics. Summary The ATP-IV guidelines present an evidence-based approach to lipid management to prevent ASCVD Remember the 4 statin risk groups A healthy lifestyle is the foundation for lowering the risk of ASCVD Clinical judgment is warranted in many scenarios There are still many questions remaining Any Questions? 7

8 What s the Skinny on the Lipid Guidelines? Pharmacy Technician Self Assessment Questions 1. Which of the following is considered clinical ASCVD (atherosclerotic cardiovascular disease)? a. High Blood pressure b. High Cholesterol c. Chronic kidney disease d. Previous stroke 2. Which of the following is the brand name for rosuvastatin? a. Lipitor b. Crestor c. Zetia d. Zocor 3. Which of the following medications has been associated with significantly reducing the risk of ASCVD? a. Ezetimibe b. Omega 3 fish oil caps c. Vitamin E d. Atorvastatin 4. According to the new guidelines, which of the following patients would likely have the greatest benefit from high intensity statin therapy? a. A 45 year old patient with an ASCVD score of 3% b. A 90 year old patient with diabetes. c. A 60 year old male with a recent heart attack. d. A 25 year old patient that smokes 1 pack of cigarettes per day. 5. Which of the following statins is NOT available as a generic at this time? a. Rosuvastatin b. Atorvastatin c. Simvastatin d. Pravastatin Key: 1. D; 2. B; 3. D; 4. C; 5. A