Hyperlipidemia FINAL

HyperlipidemiaAshish J Patel

PPE PresentationSpring 2013

Introduction1

•CVDs affects more than 70 million Americans•Hyperlipidemia is a condition of elevated lipid levels in the body•Atherosclerosis- hardening of the arteries

•Lipids are the “fats” in the bloodstream •HDL (good cholesterol), LDL (bad cholesterol), and TGs

•Increase in cholesterol levels may be due to unhealthy lifestyle, pathological conditions, certain medications

Epidemiology2

•Total cholesterol and LDL cholesterol increase throughout life

•Nearly 50% of people >20 y/o have TC of >200 mg/dL

•High-risk CV patients•History of MI (5 to 7 times higher risk of another event)

•70% of CHD occurs in patients with known CHD•Only 1/3 of treated patients are achieving their LDL goal.

Etiologies of Hyperlipidemia1,2

•Primary cause of hyperlipidemia•Familial

•Secondary cause of hyperlipidemia•Hypothyroidism•Obstructive liver disease•Nephrotoxic syndrome•Drugs: progestin, thiazide diuretics, glucocorticoids, beta-blockers, protease inhibitors, cyclosporine•Overweight•Lack of exercise and inactive lifestyle•Smoking

Symptoms of Hyperlipidemia2,3

• Mostly asymptomatic• Detected during lab

work or symptoms of CVD

• Xanthomas may form under the skin

• Extremely high levels of TG may result in pancreatitis

• May develop numerous pimple-like lesions across the body

Interpretation of Cholesterol2,4

LDL (mg/dL)**

<100 optimal100-129 Near

optimal130-159 Borderli

ne High160-189 High≥ 190 Very

High

Total Cholesterol (mg/dL)

<200 Desirable

200-239 Borderline High

≥ 240 High

HDL (mg/dL) <40 Low≥ 60 High

Triglycerides <150 Normal150-199 Borderli

ne High200-499 High

≥ 500 Very High

LDL are the primary target of therapy because elevated LDL cholesterol is a major cause of CHD.

LDL goals2,4

•Determine presence of CHD, CHD equivalent, or major risk factors.•Cigarette smoking•HTN (BP > 140/90 mmHg) or currently taking anti-HTN medications•Low HDL cholesterol ( < 40mg/dL)•Family history of premature CHD •CHD in male first degree relative <55 years•CHD in female first degree relative <65 years

•Age (men ≥ 45 years; Women ≥ 55 years)

Estimate of 10-year Risk using Framingham

•http://hp2010.nhlbihin.net/atpiii/calculator.asp•Example: A 56 y/o male smoker with a TC of 210 mg/dL, HDL of 32mg/dL, and treated BP (systolic BP of 132 mm Hg) has

•10 year risk of 25%, and therefore LDL goal of <100 mg/dL.

•Show using the Framingham Risk assessment** •Age, TC, HDL, Smoking, Systolic BP. (8 + 3+ 2 +3 + 2)

•Therefore points total is 18, which indicates 10 years risk of having a CHD is 30%.

LDL Cholesterol Goals2,4

Risk Category LDL Goal (mg/dL) LDL Level to initiate drug therapy (mg/dL)

High risk: CHD or CHD risk equivalents (10-year risk >20%)

<100 ≥100

Moderately high risk: 2+ factor and 10 year risk >10-20%

<130 ≥130

Moderate risk: 2+ risk factors (10 year risk <10%)

<130 ≥130

Lower risk: 0-1 risk factor

<160 ≥160

Therapeutic Lifestyle Changes2,4,5

•TLC initial treatment •Diet •If strictly followed, can decrease LDL by 20-30%•Restricted total fats, saturated fats, cholesterol intake•Increased soluble fiber intake

•Physical activity•≥ 30 min/day most days of the week encouraged•Caution in high risk patients or those with CAD

•Weight management

Goal of Therapy2

•The primary goal of therapy is to decrease the level of LDL to reduce the risk of:•MI•Angina•Heart failure•Ischemic stroke •Other forms of peripheral arterial disease

Statins Therapy2,4,5,6

•MOA: HMG CoA Reductase inhibition•When used alone, statins are the most potent lipid-lowering agents and among the best tolerated

•Lipid effects: LDL (↓ 18-55%) ,HDL (↑ 5-15%),TG (↓ 7-30%)•Statin Potency: Rosuva > Pitava > Atorva > Simva > Lova ER > Lova IR > Prava > Fluva

•Serious side effects: Liver damage, myopathy, rhambdomyolysis (rare), increased blood sugar, digestive problems

•PK:• Metabolism: fluvastatin (2C9), rosuvastatin (2C9 & 2C19), Provastatin (No CYP met.). All others 3A4.

• Excretion: majority Fecal excretion, however some renal excretion.

Statin Therapy Cont’d

•Contraindication: Any pre-existing liver disease, pregnancy

•Potential Drug Interactions:5

•All statins and grapefruit juice•Simvastatin and amiodarone **•All statins and gemfibrozil•Lovastatin and HIV drugs ** (protease inhibitors)

Statin Dose (mg) Change in LDL (%)

Atorvastatin

(Lipitor)

10204080

-39-43-50-60

Fluvastatin

(Lescol)

2040

80 (40 twice daily)80

-22-25-36-35

Lovastatin(Mevacor)

10204080

-21-27-31-42

Pravastatin **

(Pravachol)

10204080

-22-32-34-37

Statin Dose (mg) Change in LDL (%)

Rosuvastatin*(Crestor)

5102040

-45-52-55-63

Simvastatin(Zocor)

510204080

-26-30-38-41-47

Changes in LDL level with different doses of Statins6

Fibrates Therapy2,4,7

•Drugs: Tricor (fenofibrate), Lopid (gemfibrozil), Atromid-S (clofibrate)

•MOA: inhibits lipolysis in periphery•Typically used to treat hypertriglyceridemia•Lipid effects: LDL (↓ 5-20%), HDL (↑ 10-20%), TG (↓ 20-50%)

•Serious side effects: Nausea, stomach pain, dyspepsia, rash

•Potency: Fenofibrate> Gemfibrozil > Clofibrate

Fibrates Therapy Cont’d

•PK: Primarily excreted in the urine.•Contraindication: Severe renal disease, Severe hepatic disease, pre-existing gallstones

•Drug Interactions: •Warfarin•Oral hypoglycemic agents (eg. Sulfonylureas, metformin)

Bile Acid Sequestrants2,4,7

•Drugs: Cholestyramine (Questran, Prevalite), Colestipol (Colestid), and Colesevelam (Welchol)

•Used frequently for familial hypercholesterolemia•MOA: complexes bile to decrease liver absorption•Lipid effects: LDL( ↓ 15-30%), HDL (↑ 3-5%), TG ( No change or ↑)

•Side effects: Primarily GI effects such as constipation*, nausea, bloating

Bile Acid Sequestrants Cont’d

•PK: Orally given, but neither absorbed or altered by intestines, totally excreted in feces.

•Contraindication: TG > 500 mg/dL, bowel obstruction •This drug may be used in children and pregnant women

•Drug Interactions•Take at least 2 hours apart from warfarin, digoxin, and amiodarone

•Take only with water or orange juice before meal

Ezetimibe (Zetia)4,5,7

•MOA: inhibits cholesterol absorption in the small intestines

•When used alone, 18 % reduction in LDL•When used in combination with statins, lowers LDL by about an additional 12 to 20%•Vytorin (ezetimibe/simvastatin)

•Adverse effects: myopathy, GI problems, chest pain, fever, sore throat, HA.

•Contraindication: Liver disease, pregnancy•Taken with or without food•DI: Bile Acid Sequestrants, fibrates, cyclosporine, warfarin

Niacin4,5

•Common brand name of prescription niacin includes: Niaspan, Niacor•Available as an OTC supplement (* Necessary to talk to the doctor)

•MOA: not well defined•Lipid effects: HDL (↑ by 15-35%), LDL (↓ 5-25%), TG (↓ 20-50%)

•Side effects: Flushing*,hyperglycemia, hepatoxicity, HA

Niacin cont’d

•PK: absorbed from GI tract; eliminated in urine•Formulation:

•Available in IR, SR, and ER. •Contraindication: Chronic liver disease, hypersensitive to niacin

•Drug Interaction: Atorvastatin, Ezetimibe, alcohol, Bile acid sequestrants

•Key patient Counseling points: •Start with a low dose and tolerability•Take it with food to minimize side effects •Avoid Alcohol and warm beverages •Aspirin or NSAIDs 30 mins prior to taking niacin

Fish Oil8

•Effective for hypertriglyceridemia•OTC supplements, Lovaza*•can be taken with Statins

•Lipid effects: TG (↓ 20-50%), LDL (↑ 45%), HDL (↑ 9%)•Adverse effects: fishy taste, belching, heartburn, nausea, rash•Taking with meals can often decrease these side effects

•LIKELY SAFE for most people, including pregnant women.•Precautions: Liver disease, fish allergy, bipolar disorder, diabetes, high blood pressure, HIV/AIDS

Fish Oil cont’d

•PK: Unknown•Drug Interactions: Birth control pills, medication for high blood pressure.

•Key counseling points•Do not take if have fish allergy•Can be taken with or without food•Take with food or freeze to decrease side effects

Application to patient•CS is a 66 y/o woman. •PMH significant for silent MI and HTN.•She has CHD and has 2 major risk factors (HTN, Age).•She has a healthy diet and exercises regularly 150 minutes/week.

•She is adherent and tolerates therapy (pravastatin 40 mg, and Fish oil).

•Currently above LDL goal (<100) switching from Crestor to Pravachol, but TG and HDL are at goal.

•A more potent statin would be needed to reach goal (Crestor, Lipitor, or Zocor) or combination therapy with Ezetimibe.

•Fish oil seems to decrease TG, however it increases LDL by 45%. LDL effects in this pt. are unknown.

References

1. Rohilla, Ankur , Nidhi Dagar, Amarjeet Dahiya, and Ashok Kushnoor. "Hyperlipidemia- A Deadly Pathological Condition." International Journal of Current Pharmaceutical Research 4.3 (2012): 15-18. ijcpr.org. Web. 22 Mar. 2013.

2. Dipiro JT, Talbert RL,Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A pathophysiologic Approach. 7th ed. China: McGraw-Hill; c2011. Chapter 23, Cardiovascular disease: Hyperlipidemia; p. 385-404

3. "Hyperlipidemia - Symptoms, Treatment and Prevention." Consumer Health News, Information and Resources Updated Daily. HealthCentralNetwork, n.d. Web. 25 Mar. 2013.

<http://www.healthscout.com/ency/1/366/4. Joo, Pablo. "Primary Care | Hyperlipidemia." Columbia University in the City of New York. N.p., n.d. Web.

25 Mar. 2013. <http://www.columbia.edu/itc/hs/medical/clerkships/primcare/case/hyperlipidemia/hyperlipidemia01_05.html>

5. "High cholesterol - MayoClinic.com."Mayo Clinic. MFMER, 12 Feb. 2013. Web. 25 Mar. 2013. <http://www.mayoclinic.com/health/high-blood-cholesterol>.

6. Toth, Peter. "High-dose statin therapy: Benefits and safety in aggresive lipid lowering." The Journal of Family Practice.57.5 (2008): S29-S36. jfonline.com. Web. 23 Mar. 2013.

7. Moses, Scott. "Hyperlipidemia." Family Practice Notebook. N.p., 9 Mar. 2013. Web. 25 Mar. 2013. <http://www.fpnotebook.com/cv/Lipid/index.htm>

8. MOUTH:. "Fish oil: MedlinePlus Supplements." National Library of Medicine - National Institutes of Health. NIH, 23 July 2012. Web. 23 Mar. 2013. <http://www.nlm.nih.gov/medlineplus/drugi