Hyperlipidemia. Cardiovascular Disease. Is the leading cause of

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1 Hyperlipidemia Eric M. Pash, R.Ph. Consultant Pharmacist Diamond Drugs, Inc Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Cardiovascular Disease Is the leading cause of death in the US Affects over 64 million Americans Every minute somebody dies from a cardiovascular related event Tremendous economic burden over $400 billion annually (US) Source: American Heart Association Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Leading Causes of Mortality in the US Source: Centers for Disease Control and Prevention (CDC) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 1

2 Mortality Rates in the US Source: NCHS and NHLBI, Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Coronary Artery Disease Is the most common type of cardiovascular disease The World Health Organization estimates that dyslipidemia is associated with more than half of all global cases of ischemic heart disease and is responsible for more than four million deaths per year Also known as the silent killer Framingham Study: as cholesterol levels rise, heart disease risk increases in absence of all other risk factors Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 5 Dyslipidemia More than 100 million Americans aged 20 years and older have a total cholesterol of 200mg/dL or higher and 35.7 million have total cholesterol levels at or above 240mg/dL 71.2 million adults have LDL levels greater than or equal to 130mg/dL 35.1 million adults have HDL < 40mg/dL Source: AHA Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 2

Cholesterol A colorless substance naturally produced by the body and also obtained from diet Involved with

bad cholesterol (delivers) HDL = good cholesterol (cleans up) Total cholesterol = HDL + LDL + TG/5 Out of

16, 2015 7 Diamond Pharmacy Services Two Sources of Cholesterol Annual Educational Conference Thursday,

lead to a waxy build up of plaque in the blood vessels Narrowing and reduced blood flow can lead to a

3 Cholesterol A colorless substance naturally produced by the body and also obtained from diet Involved with energy, repair, hormone synthesis, skin and membrane structure and function Types: LDL, HDL, and TG LDL = bad cholesterol (delivers) HDL = good cholesterol (cleans up) Total cholesterol = HDL + LDL + TG/5 Out of balance if body: Makes too much Does not efficiently remove Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Two Sources of Cholesterol Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Plaques Excessive amounts of cholesterol in the bloodstream lead to a waxy build up of plaque in the blood vessels Narrowing and reduced blood flow can lead to a heart attack, stroke, or angina Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 3

4 Adult Treatment Panel (ATP) Guidelines ATP I (1988) Primary prevention of CHD if LDL mg/dL, >160mg/dL & +2 risk factors ATP II (1993) Set lower LDL goal <100mg/dL ATP III (2001) Increased emphasis on primary prevention Classified cholesterol levels Identified major risk factors (Framingham risk score) that modify LDL treatment intensity Therapeutic lifestyle modifications (TLC) Non HDL C (TG >200mg/dL) and metabolic syndrome Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Adult Treatment Panel (ATP) Guidelines continued Revised ATP III (2004) Lowered LDL C in very high risk to <70mg/dL If LDL C>100mg/dL, LDL C lowering drug + TLC (was LDL C>130mg/dL) Intensity of LDL C lowering therapy was increased in moderately high risk to 30% 40%. Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services ATP III Classification of Cholesterol Total Cholesterol < 200 mg/dl Desirable mg/dl Borderline High > 240 mg/dl High LDL Cholesterol <100 mg/dl Optimal mg/dl Near or Above Optimal mg/dl Borderline High mg/dl High > 190 mg/dl Very High HDL Cholesterol <40 mg/dl Low > 60 mg/dl High Triglycerides (TG) <150 mg/dl Normal mg/dl Borderline High mg/dl High > 500 mg/dl Very High Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 4

5 Lifestyle Interventions Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults Source: Journal of the American College of Cardiology (2013); doi: /j.jacc Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Background American College of Cardiology (ACC) and American Heart Association (AHA) collaborated with National Heart, Lung, and Blood Institute (NHLBI) to develop clinical practice guidelines for: Assessment of CV risk Lifestyle modifications to reduce CV risk Management of blood cholesterol, overweight, and obesity in adults Task Force, or expert panel, reviewed clinical evidence (randomized, meta analysis, observational studies) and made recommendations when the evidence supported or documented lack of supporting evidence Recommendations are graded based on level of evidence Strong (A), moderate (B), weak (C), recommend against (D), expert (E), no recommendation (No) Limited scope to atherosclerotic cardiovascular disease (ASCVD) risk Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 5

Major Changes Targeting specific LDL cholesterol targets is no longer recommended Clinicians should determine if a patient falls into one of four highrisk groups and initiate the appropriate statin

compliance No dose titration New risk calculator 10 year ASCVD risk: http://my.americanheart.

6 Major Changes Targeting specific LDL cholesterol targets is no longer recommended Clinicians should determine if a patient falls into one of four highrisk groups and initiate the appropriate statin therapy for that group High Intensity or Moderate Intensity Low Intensity may be considered if the recommended intensity is not tolerated Follow up monitoring should be done to ensure medication compliance No dose titration New risk calculator 10 year ASCVD risk: Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Major Changes continued Other lipid modifying medications are discouraged, with a few exceptions High statin doses are favored over multi drug therapy Wider target population* Currently: 15.5% Estimated to increase to 31% *Statistics from: guidelines for statin users will increase prescription drug users 50010/. Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services AHA s Life s Simple Seven Avoiding smoking Maintaining appropriate weight, physical activity, and diet Pursuing ideal levels of blood pressure, blood glucose, and cholesterol Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 6

Lifestyle Modifications Stop Smoking Smoking is the number one avoidable cause of cardiovascular death The risk of heart disease is reduced by 50% after one year of smoking cessation, and after 15

7 Lifestyle Modifications Stop Smoking Smoking is the number one avoidable cause of cardiovascular death The risk of heart disease is reduced by 50% after one year of smoking cessation, and after 15 years the risk is comparable to that of a non smoker Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Lifestyle Modification Modification Recommendation Cholesterol Changes Smoking Cessation Use patch, gum, or other modality of choice Increases HDL by 4% (within weeks); Reduces ASCVD 10 year risk Regular Exercise Reduced Alcohol Consumption With doctor s permission, perform minutes of exercise 4 6 times per week Women: 1 drink/day Men: 2 drinks/day Control Blood Pressure CAD: prevention: < 140/90 CAD: < 130/80 Reduces TG & increases HDL by 5 10% Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Life Style Modifications Modification Recommendation Cholesterol Changes Heart healthy Diet Reduce intake of saturated and trans fats Reduces LDL by 5% and increases to <7% of calories HDL by 20% Increase intake of fiber: 3oz. oats/day Increase intake of nuts, soy, protein, plant sterols, and omega 3 fatty acids DASH eating plan: encourages fruits, vegetables, whole grains, fish, poultry, nuts, vegetable oils and limits sodium, red meats, sugary beverages, and sweets Weight Control BMI calculator (National Heart, Lung, and Blood Institute NHLBI) ional/lose_wt/bmi/bmicalc.htm. Attempt lifestyle modifications for 3 months before initiating drug therapy Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 7

Pharmacotherapy Annual Educational Conference Thursday, April 16, 2015 22 Diamond Pharmacy Services Drug Therapy: Two Pathways Targeted Annual Educational Conference Thursday, April 16, 2015 23

for lipidlowering medications are never filled Approximately 75% of new statin users stop therapy by the end of the first year (approximately one third do so without consulting their doctor) Due to

8 Pharmacotherapy Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Drug Therapy: Two Pathways Targeted Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Need for Aggressive Control Less than over half of all patients at risk for having established heart disease receive lipid lowering therapy One third of all prescriptions for lipidlowering medications are never filled Approximately 75% of new statin users stop therapy by the end of the first year (approximately one third do so without consulting their doctor) Due to side effects (62%) Due to cost (17%) Due to lack of efficacy (12%) Sources: AM J Cardiol 1998; Pharmaco therapy 2001; Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 8

9 Currently Available Lipid Lowering Agents Bile acid binding resins (BABR s) Fibric acid derivatives ( fibrates ) Nicotinic acid (niacin) HMG CoA reductase inhibitors (statins) Cholesterol absorption inhibitor Omega 3 fatty acid supplements (fish oils) Adjunctive therapy / miscellaneous Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services BABR s Inhibits absorption of bile acids from the gut, thus preventing hepatic production of cholesterol Drug interactions Decreased absorption of many other drugs Important to space apart dosing No evidence supporting CHD prevention (use as addon therapy instead) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services BABR s Cholestyramine powder (Questran, Prevalite ) LDL HDL TG Side Effects* 9 28% 4 8% Colestipol powder (Colestid ) 5 26% Colesevelam tablets (Welchol ) 12 19% 3 8% Increases 11 28% Increases 12 15% Increases 5% Bloating Flatulence Constipation Nausea Dyspepsia Adapted from Pharmacist s Letter Detail Document 2010 (220802) *To minimize GI side effects, take with cold non carbonated liquids and increase bulk in diet Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 9

10 Fibric Acid Derivatives Inhibits liver production of VLDL and increases TG removal from the blood Drugs of choice for extremely elevated TG levels (which can lead to pancreatitis if left uncontrolled) Drug interactions Statins increased risk of myopathy Warfarin (Coumadin ) bleeds can occur Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Fibric Acid Derivatives Fenofibrate (Lipofen, Tricor,Antara ) (daily dosing) Gemfibrozil (Lopid ) (twice daily dosing) Fenofibric acid (Trilipix ) (daily dosing) LDL HDL TG Side Effects 21% 11% 29% 6% 31% 5% 16% 31% Adapted from Pharmacist s Letter Detail Document June 2010 (220802) Dyspepsia Abdominal pain Glucose intolerance Gallstones Myositis /myopathy (gemfibrozil > fenofibrate) Increased liver enzymes (fenofibrate > gemfibrozil) Sources: AM J Cardiol 2004, 2008; Trilipix Package Insert. Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Niacin (Nicotinic Acid) B vitamin that alters the liver s production of VLDL and suppresses the synthesis / secretion of LDL Most effective at raising HDL levels (at low doses) Much higher doses are needed to significantly lower LDL Often used as add on therapy or as an alternative (i.e. in statin intolerant patients) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 10

11 Niacin (Nicotinic Acid) HDL LDL TG Side Effects Niacin 17 26% 14 17% 13 28% Flushing upon initiation of therapy and dose increases Rash Itching Dyspepsia Diarrhea Anorexia Lethargy Peptic ulcer disease Hyperuricemia Hyperglycemia (modest)* Dose related hepatotoxicity Adapted from Pharmacist s Letter Detail Document 2010 (220802) *Niacin is still acceptable for use in diabetics (monitor) Sources: JAMA 2000; Am J Health Syst Pharm Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Immediate Release Niacin (IR) Niacor Prescription and OTC versions Absorbed over one to two hours GI side effects take with food Flushing: seen in almost all patients (when given at doses greater than 2 grams per day) Capillaries dilated within minutes and lasting minutes or longer Redness, itchiness, warmth, rash, headache Many discontinue treatment (25 50% at doses of 3 grams per day or more) Self limiting most develop tolerance within a few weeks of continued use Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Immediate Release Niacin (IR) continued To minimize flushing associated with rapid niacin absorption: Titrate slowly (125mg twice daily up to 1 2 grams twice daily) over eight weeks or longer Give plain aspirin (81 325mg) or ibuprofen 30 minutes prior (enteric coated ASA sooner) if tolerated and not contraindicated minimizes incidence, severity, and duration of flushing events Give with low fat snacks / meals in divided doses Avoid hot beverages, alcohol, or eating spicy foods Take at bedtime Avoid hot showers after dosing Do not stop and start (symptoms can reappear) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 11

Sustained Release Niacin (SR) Niacinamide (nicotinamide) Nicobid, SloNiacin Dietary supplement (not to be confused with OTC versions) Preparations vary widely in strength, efficacy, and safety

common than with IR Flushing: less common than with IR (by design) GI side effects Annual Educational Conference Thursday, April 16, 2015 34 Diamond Pharmacy Services Extended Release Niacin (ER)

12 Sustained Release Niacin (SR) Niacinamide (nicotinamide) Nicobid, SloNiacin Dietary supplement (not to be confused with OTC versions) Preparations vary widely in strength, efficacy, and safety Absorbed over 12 hours Not approved by FDA for the treatment of hyperlipidemia Too high of doses would be required Dose related hepatotoxicity: 2 grams or more/day given over several months More common than with IR Flushing: less common than with IR (by design) GI side effects Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Extended Release Niacin (ER) Niaspan Available by prescription only Unique balance between IR and SR formulations Released over eight to 12 hours Most favorable safety profile Less flushing, minimal hepatotoxicity AIM HIGH study (stopped early) No additional benefits seen in the reduction of cardiovascular complications when given with a statin A small increase in the number of ischemic strokes was observed Source: NIH Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Flushless / No Flush Niacin Inositol Minimal cholesterol effects (requires too high of doses) Difficult to achieve desired plasma drug concentrations Not recommended Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 12

Statins Comprises 85% of all cholesterol lowering drugs dispensed Taken by more than half of all Americans over 50 years old OTC versions are available in Europe Sources: Business Week 2005; Walters

13 Statins Comprises 85% of all cholesterol lowering drugs dispensed Taken by more than half of all Americans over 50 years old OTC versions are available in Europe Sources: Business Week 2005; Walters Kluwer 2011; Nature Reviews Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Statins First line treatment for the reduction of LDL Most effective lipid lowering agents for primary and secondary prevention of heart disease (JUPITER Trial 44% reduction in CV events) improved outcomes for ischemic stroke Antioxidant and anti inflammatory effects Reduces blood vessel wall thickness Diminishes plaque formation and promotes plaque stability (antithrombotic activity) Improves impaired endothelial vasodilator response Reduces C reactive protein Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Statins Underutilized or overprescribed? Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 13

14 When to Dose Statins Cholesterol production is highest overnight Older agents should be dosed in the evening or at bedtime Pravastatin (Pravachol ) Lovastatin (Mevacor ) Newer agents can be dosed at any time during the day Simvastatin (Zocor ) Atorvastatin (Lipitor ) Rosuvastatin (Crestor ) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Statin Comparison Average Treatment Results LDL HDL TG Rosuvastatin (Crestor ) 45 63% 8 14% 10 35% Atorvastatin (Lipitor ) 39 60% 5 9% 19 37% Simvastatin (Zocor ) 26 47% 8 16% 2 33% Lovastatin (Mevacor ) 21 42% 2 8% 6 10% Pravastatin (Pravachol ) 22 37% 1 12% 4 24% Fluvastatin (Lescol ) 22 35% 12 19% 3 11% Pitavastatin (Livalo ) 38 45% 5 8% 15 19% Adapted from Pharmacist s Letter Detail Document June 2010 (220802) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Efficacy and Dosing Equivalency of Statins Decrease in LDL cholesterol (%) Dosing equivalency of statins (mg/d) Fluvastatin Fluvastatin Pravastatin XL Lovastatin Lovastatin ER Simvastatin Atorvastatin Rosuvastatin Simvastatin/ ezetimibe / / / / Abbreviations: ER, extended release; LDL, low density lipoprotein; XL, extended release Source: Formulary. Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 14

Statin Effects on LDL Annual Educational Conference Thursday, April 16, 2015 43 Diamond Pharmacy Services Potential Side Effects of Statins Dose related liver enzyme concentrations (>3x ULN) A,B

15 Statin Effects on LDL Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Potential Side Effects of Statins Dose related liver enzyme concentrations (>3x ULN) A,B Creatinine kinase elevations which can lead to muscle damage (>10x ULN) approximately 1% of users Myalgia and myopathy muscle aches, tenderness, pain, and weakness approximately 10% of users C Generally mild Often seen between three weeks and three months Usually subsides upon discontinuation within one to two months Rhabdomyolysis (muscle wasting) < 0.1% of users C Muscle toxicity Can lead to acute renal failure Brown/dark red urine Reversible A Baycol pulled from market in 2001 for associated liver problems (>10x ULN); B Routine standard LFT testing is no longer recommended for statins (of no additional benefit); C Zocor (simvastatin) FDA advisory mg dose = increased risk myopathy/rhabdomyolysis. Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services How to Lessen Adverse Effects of Statins Use lowest doses possible Take with food to minimize GI side effects Consider pravastatin (Pravachol ) or fluvastatin (Lescol ) less side effects and fewer drug interactions Dose rosuvastatin (Crestor ) and atorvastatin (Lipitor ) every other day (or possibly give rosuvastatin once weekly) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 15

Statin Interactions Drug drug interactions: responsible for one half of all statin adverse drug reactions Increased bleeding risk with warfarin (Coumadin ) use caution when starting or stopping

Verapamil (Calan ) Diltiazem (Cardizem ) Amiodarone (Cordarone ) Pravastatin (Pravachol ) is the cleanest of the statins (due to its water solubility) Annual Educational Conference Thursday, April

16 Statin Interactions Drug drug interactions: responsible for one half of all statin adverse drug reactions Increased bleeding risk with warfarin (Coumadin ) use caution when starting or stopping Increased risk of rhabdomyolysis with other lipid lowering drugs, certain antibiotics, and other enzyme inhibitors Gemfibrozil (Lopid ) High dose niacin Erythromycin Clarithromycin (Biaxin ) Verapamil (Calan ) Diltiazem (Cardizem ) Amiodarone (Cordarone ) Pravastatin (Pravachol ) is the cleanest of the statins (due to its water solubility) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Statin Interactions Addressing drug drug interactions: Hold/restart the statin Change to a different statin Lower the statin dose Change the interacting drug Switch to a different class of cholesterol reducing agent Add another cholesterol reducing agent Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Statin / Food Interactions Grapefruit juice interactions Primarily seen with simvastatin (Zocor ) due to its metabolic pathway Dosing apart doesn t help Important to maintain a steady, consistent diet Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 16

17 Possible Expanded Role of Statins Certain cancers Hepatitis C Alzheimer s dementia Venous thromboembolism Multiple sclerosis Diabetes Loss of vision Glaucoma Infections and respiratory illness (sepsis, pneumonia, bacteremia) Protection against cardiovascular problems in those with normal cholesterol having other risk factors* Macular degeneration Regression of atherosclerotic plaques** A marked deterioration of glycemic control has been observed in some patients taking atorvastatin (Lipitor ) *Rosuvastatin (Crestor ) is FDA approved to slow the progression of atherosclerosis **High-dose, intensive statin therapy (SATURN Study) Sources: J Atheroscler Thromb 2006; Science Daily 2011; NEJM Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Cholesterol Absorption Inhibitor Ezetimibe (Zetia ): Inhibits cholesterol absorption from the intestines Lowers LDL only moderately (as monotherapy) Concern may not stabilize coronary arterial plaques ENHANCE trial significant reductions in LDL and CRP, however not proven to prevent CHD IMPROVE IT trial larger trial which did not show benefit in CHD prevention Source: J Am Coll Cardio Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Cholesterol Absorption Inhibitor LDL HDL TG Side Effects Ezetimibe (Zetia ) 18% 1% 8% Diarrhea Arthralgia Fatigue Cough Adapted from Pharmacist s Letter Detail Document June 2010 (220802) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 17

18 Fish Oils (Omega 3 Fatty Acids) The human body is unable to naturally produce omega 3 fatty acids Omega 3s are obtained through the diet (fish, certain plants, or supplementation) The AHA recommends that all individuals consume fish at least twice weekly to help prevent heart disease* *Subject of debate improved cardiovascular health in fish eaters may be due to overall healthier diets in general and not due to fish consumption specifically Source: Am J Cardiol Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Fish Oils (Omega 3 Fatty Acids) Significant TG reductions (effects on LDL inconsistent / little to no improvement or benefit seen) Almost a universal benefit seen in heart failure Prevents secondary heart attacks and lowers the heart rate Also has anti inflammatory, mild antihypertensive, mild antiarrythmic, and antiplatelet effects (decreased Lp(a)) Expanded role arthritis, skin problems, Alzheimer s disease, diabetic kidney damage, obesity, immune disorders, methane emissions in livestock Source: Am J Cardiol Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Fish Oils Available as OTC (non prescription) dietary supplements (capsules, liquids) and prescription omega 3 (capsules) Contains polyunsaturated fatty acids EPA, DHA Found in fatty fish oils and shellfish Recommended dosages for TG reduction = 2 4 grams/day Recommended dosages for secondary cardiovascular disease prevention and for treating heart failure = 800 1,500 mg/day (600mg 2 grams/day per other sources) Source: Am J Cardiol Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 18

OTC Fish Oils Formulations vary in content, purity, and potency Contains differing amounts of EPA and DHA Read product labels carefully Annual Educational Conference Thursday, April 16, 2015 55

19 OTC Fish Oils Formulations vary in content, purity, and potency Contains differing amounts of EPA and DHA Read product labels carefully Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Unregulated OTC Fish Oils Dietary fish oil supplements Many boast 100% fish oil claims Have little to no benefit Contain high levels of saturated fats May contain harmful impurities and higher concentrations of contaminants (i.e. mercury) Accidental poisonings can occur Contain inconsistent levels and little to no EPA or DHA May require 10 or more capsules a day to realize therapeutic benefits Inexpensive (pennies per day i.e. $ /capsule) Do not self treat for high TG (higher doses required, increased risk of adverse effects) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Regulated OTC Fish Oils Pharmaceutical grade, ultra refined products Preferred OTC fish oil supplements Impurities and contaminants have been removed Consistent levels of EPA and DHA Contains 325 to 450mg of both EPA and DHA For cardiovascular health benefits, take 1 4 capsules/day Costs $1 2/day Primary side effects slight fishy odor Do not self medicate for high TG (higher doses required, increased risk of adverse effects) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 19

Lovaza Available by prescription only Highly purified product One capsule contains: 465mg EPA 375mg DHA 4 grams/day recommended for TG reduction Take two capsules twice daily or four capsules all at

20 Lovaza Available by prescription only Highly purified product One capsule contains: 465mg EPA 375mg DHA 4 grams/day recommended for TG reduction Take two capsules twice daily or four capsules all at once each day Cost per day = approximately $10 Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Lovaza Omega 3 acid ethyl esters (Lovaza ) LDL HDL TG Side Effects* Increases 44.5% 9% 45% Nausea Diarrhea GI upset Poor aftertaste Burping Reflux/heartburn Vitamin E deficiencies *Omega 3 s can also increase the bleeding potential of aspirin, warfarin (Coumadin ), and clopidogrel (Plavix ) Adapted from Pharmacist s Letter Detail Document June 2010 (220802) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services To Lessen GI Effects of Fish Oil Products Take with meals Divide doses Start at a lower dose and gradually increase the dose Use enteric coated preparations Freeze non enteric capsules Select a more consistent, purified product Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 20

21 Choosing a Therapy Class LDL HDL TG Statins 21 63% 1 19% 2 37% Fibrates 21% 6 11% 29 31% Niacin 14 17% 17 26% 13 28% Bile resins 5 28% 3 8% Increases 5 28% Cholesterol absorption inhibitor 18% 1% 8% Omega 3 fatty acids Increases 44.5% 9% 45% Adapted from Pharmacist s Letter Detail Document June 2010 (220802) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Combination Therapy Up to 25% of statin users do not reach goal or experience side effects Ongoing debate: increase the dose of statins or consider adjunctive therapy? Combination therapy allows for lower doses of each, thus decreasing risk of certain side effects, however drug interactions are more likely to occur Triple therapy?? Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Ezetimibe / simvastatin (Vytorin ) Additive LDL lowering effects Reduces the amount of cholesterol absorbed by the body and blocks the production of cholesterol Side effects and drug interactions are comparable to statin monotherapy May not stabilize coronary arterial plaques Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 21

Niacin ER / Lovastatin (Advicor ) Increases HDL, decreases LDL, and decreases TG Not indicated for initial therapy Side effects

Pharmacy Services Niacin ER / Simvastatin (Simcor ) A more potent Advicor Increases HDL, decreases LDL, and decreases TG Not

22 Niacin ER / Lovastatin (Advicor ) Increases HDL, decreases LDL, and decreases TG Not indicated for initial therapy Side effects and interactions are similar to the individual components Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Niacin ER / Simvastatin (Simcor ) A more potent Advicor Increases HDL, decreases LDL, and decreases TG Not indicated for initial therapy Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Amlodipine / Atorvastatin (Caduet ) Calcium channel blocker and a statin Used to treat hypertension and high cholesterol Side effect profile is similar to the individual drug components Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 22

23 Combination Therapy % Change from Baseline* LDL HDL TG Statin + BABA 10 20% 0 9% Statin +niacin 1 10% 15 24% 12 24% Statin + fibrate 0 6% 9 17% 20 40% Statin + ezetimibe 25% 3% 14% Statin + omega 3 0.7% Increase 3% 30% *Further changes Adapted from Pharmacist s Letter Detail Document June 2010 (220802) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Adjunctive Cholesterol Treatment Folic acid and vitamins B6 and B12 Homocysteine is a highly reactive amino acid Concentrations are elevated in cardiovascular disease Injures endothelial cells, alters platelet activity, and inhibits vasodilation Elevated homocysteine may increase LDL deposition and promote atherosclerosis Supplementation has been found to reduce serum homocysteine levels Not shown to reduce cardiovascular disease risk Antioxidants vitamins A, C, and E and beta carotene Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Adjunctive Cholesterol Treatment Garlic: Can decrease total cholesterol and LDL by 10% Modest blood pressure lowering effects and clot prevention Supplements vary Take one half to one fresh clove per day Little supporting evidence of efficacy Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 23

24 Adjunctive Cholesterol Treatment Alcohol Increases HDL, however also increases TG Two drinks per day Chocolate (cocoa) Decreases LDL and total cholesterol Six grams per day (approximately one seventh of a Hershey bar) Resveratrol Found in red wine, red grape skins, mulberries, cranberries, huckleberries, and rhubarb (contains polyphenols) Antioxidant and antiplatelet effects improves endothelial function, vasodilates, improves muscle perfusion Possible role in prevention of cardiovascular disease, diabetes, Alzheimer's disease, colon and prostate cancers Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Adjunctive Cholesterol Treatment Red rice yeast (dietary supplement) A natural statin Chinese fermented product with claims of improved blood circulation Unregulated products purity and uniformity concerns Lack of controlled trials Contains monacolin K, the active ingredient in lovastatin (Mevacor ) Contains mg/capsule (varies) Typically dosed as two capsules twice daily = provides approximately 6mg of lovastatin per day Reduces LDL (up to 25 35%), total cholesterol ( %), and TG (16%) No significant changes in HDL Well tolerated, mild side effects, still potentially dangerous Myalgias, myopathy Kidney damage (due to cirinin) Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Summary 2013 ACC/AHA Guideline on Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults (2014) Lifestyle modifications (TLC) are recommended prior to and with drug therapy Fixed dose statin dosing to achieve LDL C or non HDL C goals Introduces low intensity, moderate intensity, and high intensity statin drugs and doses Evidence (or lack there of) that use of non statin therapy to additionally lower non LDL C once target was achieved lowered ASCVD outcomes TG >500mg/dL treated if benefits outweigh risk Appropriate intensity statin therapy should be used to reduce calculated 10 year ASCVD risk in those most likely to benefit Risk calculator Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 24

25 Summary continued Extended release niacin is good at increasing HDL and has a favorable safety profile Fish oils significantly reduce TG levels but can increase LDL levels Combination therapy allows for lower dosing, which may reduce the risk for side effects, however drug interactions are more likely Adjunctive cholesterol treatments exist, however their efficacy is supported by few or no studies Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services Additional Resources American Heart Association Mayo Clinic National Library of Medicine Centers for Disease Control American Academy of Family Physicians Annual Educational Conference Thursday, April 16, Diamond Pharmacy Services 25

Cholesterol. Medicines To Help You

Cholesterol. Medicines To Help You Medicines To Help You Cholesterol Use this guide to help you talk to your doctor, pharmacist, or nurse about your cholesterol medicines. The guide lists all of the FDA-approved products now available to