48. Dyslipidemia

ACC/AHA

4 key Pt grps low, mod, high to reduce LDL NON-Statins NOT recommended -- Unless statin NOT tolerated 2016 update recommend -- ezetimibe (reduce CV events)(IMPROVE-IT) -- PCSK9 inhibitors

dyslipidemia guidelines

ACC/AHA (rsik levels) NLA (target levels)

Pt counsleing

ALL cholesterol meds -- lifestyle changes Statins -- muscle problems -- dark urine liver damage -- Zocor, lescol in evening -- Mevacor w/ pm meal -- Altoprev QHS -- Grapefruit may lead to increase amounts in body -- NO pregos and boobi feeders Ezetimibe -- qd w/ or w/o food Fish oil -- take whole -- taste and indigestion Niacin -- Take w/ food Niaspan QHS -- flushing -- avoid EtOH -- Mild increase in BG Bile acid Sequestrants -- fluid intake w/ packets -- PLENTY of water -- obstruction of biliary and bowels -- separate from meds and ADEK Fibrates -- PCSK(

GLobal risk assessment tool

ASCVD 10yr risk tool Est. the risk of MI stroke Death in 10years Use -- Aga -- gender -- race -- TC -- HDL -- Systolic BP -- HTN meds >/= 7.5% and 40-75yo use STATIN According the the ACC/AHA Blood Cholesterol Guidelines, the Global Risk Assessment tool should be repeated every 4-6 years in low risk patients.

Dyslipidemia

Abnormalities in levels Increase in -- TC -- LDL -- TG Decrease in -- HDL CAN BE -- inherited (primary/familial) -- Secondary (poor Hx choices)

Statin Drug interactions

All -- Increase myopathies w/ fibrates (gemfibrozil) AND Niacin >/= 1gm AND Colchicine The maximum dose of lovastatin (a major 3A4 substrate) is lower when a patient is taking verapamil. Know which drug interactions will necessitate a lower max dose of statins like lovastatin and simvastatin.

Biaxin, Lopid and VFEND, as well as itraconazole and ketoconazole should be avoided with simvastatin (and lovastatin) therapy.

Biaxin = clarithromycin -- CYP inhibitor VFEND = voriconazole -- CYPinhibitor Gemfibrozil -- CI in statins due to muscle toxicities

PCSK9

Binds LDL receptors on liver to promote LDLR degredation. (LDLR clears LDL) Indicated for HeFH/HoFH Monoclonal Antibodies Alirocumab (Praluent) -- SC q 2 weeks -- HeFH and ASCVD Evolovumab -- Repatha (sureclick, pushtronix) -- HeFH, HoFH, ASCVD -- give SC q 2weeks or q 1 month Allergic reactions Injection site reactions Monitor -- LDL at baseline and 4-8weeks 14k.yr$ Decrease LDL 60%, non-HDL 35%, apoB 50%, TC 36% ApoB is the primary apolipoprotein of chylomicrons, VLDL, IDL, and LDL particles, which is responsible for carrying fat molecules,

Lifestyle modifications

Conusme -- vegetables -- fruits -- whole graine -- high fiber -- fish and their oils -- limit 5% saturated and 0% Transexual fatties Limit sugar, salt aerobic activity 3-4x/wk 40 min session BMI <25 No tabacoo and EtOH

Thiazides are associated with increases in LDL and triglycerides. Loop diuretics can cause increases in triglycerides and total cholesterol.

Crestor, Lipitor, Livalo, Lescol XL and Pravachol can be taken at any time of day.

Cholesterol

Does not dissolve in bLood need lipoprotein transport. 4 types -- LDL -- HDL -- VLDL -- TG (total cholesterol) Non-HDL = TC -HDL > atherogenic Dx w. > non-HDL, LDL, TG -- Fatty deposits accumulate (atherosclerosis)

Primary/ familial dyslipidemia

FH (familial Hypercholesterolemia) -- genetic defects results in hyper cholesterol levels -- HeFH (heterozygous) -- HoFH (homosexualzygous HRD to Tx)

Fenofibrates CI

Gallbladder Disease Severe liver Dx Nursing mothers severe kidney Dx Rapaglinide (A meglinitide) CI w/ Lopid

NON-Statin Path

High risk Pt w/ ASCVD use ezetimibe and PCSK9i

Statin and Muscle damage

If muscle symptoms resolve within 2-4 weeks of discontinuing the statin, it is recommended to restart the same statin at the same or lower dose.

A patient begins Niaspan and finds she suffers from red, itchy skin. She does not believe she can tolerate the medicine. Which of the following statements are correct that the pharmacist should provide to the patient?

If the physician permits it, take 325 mg of aspirin 30 minutes before the Niaspan; this should help reduce the problem. Avoid alcohol, hot beverages and spicy food near the time of the medicine. This problem should lessen as she takes the medicine continuously. Take the Niaspan at bedtime; most of the problem will occur while she sleeps. Flushing with niacin is prostaglandin-mediated therefore, an antihistamine such as Benadryl will not help.

Statin

Inhibit HMG-CoA CI = Active liver Dx, pregos, boobie fed, CYP3A4 inhibitors (simva., lova.) Cyclosporine Warning -- muscle effects (myopathy, rhabdomyolysis) -- Old, Cyp3A4, niacin, Hypothyroid, renal -- DM increase A1C and FBG (use > risk) SEs = Myalgias, arthralgias, myopathy (muscle Dx) Monitoring -- Lipid panel 4-12wks after initiation -- Baseline LFTs Notes -- NO pregos!!! -- Crestor, Lipitor, Pravachol, Pitavastatin, fluvastatin take anytime -- CrCl <30ml/min use lower does Lova, simva, rosu. -- Pitavastatin CrCl <60 use low dose -- Rosuvastatin 2x higher in Asains- use 5mg start dose LIPID EFFECTS -- Decrease LDL 20-55%, TG 10-30% -- Increase HDL 5-15%

4 statin benefit grps

Initiate statin if 1) Presence of ASCVD -- ACS, MI, angina, revasc., stroke, TIA, PAD (athero) 2) LDL >/= 190 mg/dL 3) DM @ >40-75yo w/ LDL 70-189 mg/dL 4) 40-75yo w/ LDL 70-189 mg/dL w/ ASCVD risk >/= 7.5%

Statin generic names

Livalo is pitavastatin. Vytorin contains simvastatin (HMG-CoA inhibitor) and ezetimibe (blocks absorption of cholesterol at the brush border in the small intestine).

Fish oils

MOA reduce hepatic synthesis of TGs FOR adjunct to diet in Pts TG >500 Omega 3 Acid Ethyl Esters (Lovaza) -- 465mg EPA, 375mg DHA Icosapent ethyl (Vascepa) -- w/ food Omega-3-carboylic acids (Epanova) -- 850mg EPA/DHA Omega-3- ethyl esters (omtryg) -- 465mg EPA, 375 DHA Warnings -- sensitive to shellfish -- Increase LDL SEs = Eructation (burping) dyspepsia, taste ONLY Rx products approved for TG lowering when TGs >500 INCREASED bleed risk!!! Decrease TGs 45% Increase HDL 9% CAN increase LDL Except Vescepa MAY PROLONG bleed time

Myalept is indicated in leptin deficiency with congenital or acquired generalized lipodystrophy.

Myalept (metreleptin) is used to treat complications caused by leptin deficiency in people who have lipodystrophy.

Fibrates

PPAR-alpha activators, increase apoC-II and apoA-II. Lowers TGs significantly and if they are high than LDL and HDL will increase ACCORD trial no difference in CV events in Pts treated w/ fibrate + simva. compared to simva. alone The fenofibrates come in different strengths and often with different delivery mechanisms. If the pharmacist wants to dispense a generic, he/she may need to call prescriber for a close strength and try to match one with a similar delivery technology. Some formulations, such as the micronized formulations, are used to improve bioavailability.

Lipoprotein (Cholesterol) types and values

Recommend fasting for levels (9-12hrs) If fasting NOT reported Friedewald Equations used. -- LDL = TC - HDL - (TG/5) only w/ TG <400 -- If not fasting TGs will be increased leading to false low LDLs

Natural Products

Red yeast rice do not use Fish oil used for TGs Niacin

Bile acid sequestrants/ binding resins

Removes bile acids from system CI = Cholestyramine (Questran, Prevalite) - biliary obstruction -- Colesevelam (Welchol) - bowel obstruction, TG >500, Hx of hypertriglycerides and pancreatitis Warning -- bleed risk due to vitK deficiency SEs = constipation, abdominal Pain, cramp, gas, bloat, INCREASE TGs DO NOT USE TG >300 Cholest. packet - 2-6oz water/non-carb. liquid. hold in mouth casues erosion Coles. packet - 4-8 oz water or juice or soft drink Colest. Pack - 3 oz water Colesevelam OPTION in PREGO!!! lipid effects -- Decrease LDL 10-30% -- Increase HDL 3-5%, TG 5% DDIs -- Take other meds 1-4hrs bf or 4-6hrs after -- Decerase ADEk Welchol can lower hemoglobin A1C ~0.5% by decreasing postprandial blood glucose. Bile acid sequestrants can cause increased triglycerides in some cases.

Niacin

Slo-Niacin has the highest risk of hepatotoxicity. Niacin can raise uric acid levels and should be used with caution in patients with gout. Slo-Niacin Sustained-release and Niaspan extended-release niacin have less (but still significant) flushing and itching. MONITOR -- LFTs -- Blood sugar -- INR -- Uric acid (gout)

Niacin immediate-release must be started very slowly or it will not be tolerated. Niacin extended-release (Niaspan) is started at 500 mg QHS x 4 weeks (after a light snack), followed by 1,000 mg QHS x 4 weeks, can increase to 2,000 mg QHS. The maximum dose of this formulation is 2 grams daily, versus 3 grams daily for the immediate-release, according to the ACC/AHA guidelines.

Start with 100 mg TID and increase gradually, as tolerated to 3 grams per day, divided in 2-3 doses.

Drug Tx

Statins DOC for Tx non-HDL and LDL increase -- SEs = Increase DM and Myalgias Intolerant statin Pt -- USe liver damage drugs -- Niacin, fibrates, ezatimibe MONITOR -- liver enzymes -- AST 10-40 u/L -- ALT 10-40u/L -- STOP statin if > 3x upper limit of normal (+120ish) PCSK9i -- for FH -- for additional LDL decrease -- Block protein that binds the LDL receptor in the liver -- SC inj. -- monoclonal antibodies

An estimated 10-year ASCVD risk score of ≥ 7.5% is an indication to start primary prevention with statin therapy.

Statins should be stopped once the LFTs are 3 times above the upper limit of normal (ULN).

These represent the patient types that benefit from moderate-intensity statin treatment according to the ACC/AHA Blood Cholesterol Guidelines.

Those unable to tolerate high-intensity statin therapy A 80 year old patient who is S/P MI A 45 year old patient with diabetes and a LDL of 140 mg/dL and no other comorbidities; 10-year ASCVD risk score is 6.5%

Ezetimibe

inhibits cholesterol at brush border of small intestine. IMROVE-IT showed decreased CV events in combo w/ statin. Zetia + simvastatin (Vytorin) CI = Used w/ statins in liver Dx and pregos/ boobie fed Warning = hepatic impairment, myopathy increased with statins SEs = Diarrhea, URTIs, muscle pain sinusitis Monitor -- LFTs at baseline used w/ statin MonoTx -- Decrease LDL 18-23%, TG 5-10% -- Increase HDL 1-3% DDIs -- cyclosprorine (increase levels) -- Bile acid sequestarents (decrease levels) -- Avoid gemfibrizol

Secondary/ Acquired

lifestyle cholesterol elevations include -- LDL > 190 mg/dL -- TG >/+ 500 mg/dL 2ndry causes -- Diet -- Drugs -- Disease -- Disorders

Background

liver produces cholesterol and uses it to make bile acids. This gets ducted to the small intestines for fat absorption. This then gets recycled and sent back to liver (cholesterol) Ezetimibe blocks recycle of free cholesterol. Bile acid sequesterants block recirculation of bile salts decreasing cholesterol.

Atorvastatin (and others) has a long half-life and does not need to be given in the evening to maximize inhibition of cholesterol synthesis which peaks in the early morning hours.

simva has the shortest and should be taken at night