Drugs for lipids

Treatment Guidelines from The Medical Letter® Published by The Medical Letter • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Drugs for Lipids p The Medical Letter ® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 FORWARDING OR COPYING IS A VIOLATION OF US AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 Treatment Guidelines from The Medical Letter® Published by The Medical Letter • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 12 (Issue 137) January 2014 www.medicalletter.org Take CME exams Tables Statins Non-Statins Adverse Effects of Cholesterol-Lowering Drugs Statin Combination Products Page Page Page Page Drugs for Lipids Related article(s) since publication New guidelines from the American College of Cardiology and American Heart Association no longer recommend using specific cholesterol targets in the treatment of hyperlipidemia.1 HMG-CoA reductase inhibitors (statins) are the lipid-lowering drugs of first choice for treatment of most patients with atherosclerotic cardiovascular disease They can decrease the incidence of major coronary events and death in such patients Taken as an adjunct to diet, exercise, and smoking cessation, statins can also reduce the risk of first cardiovascular events and death in patients with risk factors such as elevated levels of low-density lipoprotein cholesterol (LDL-C) and diabetes Their  benefits in these patients clearly outweigh their adverse effects Combining a statin with another LDL-C lowering drug, such as colesevelam, niacin, or ezetimibe, can reduce LDL-C levels further than a statin alone, but studies demonstrating that such combinations improve clinical outcomes are lacking Lipid-lowering drugs must be taken indefinitely; when they are stopped, plasma lipoproteins return to pretreatment levels STATINS HMG-CoA reductase inhibitors (statins) inhibit the enzyme that catalyzes the rate-limiting step in cholesterol synthesis The subsequent reduction in hepatic cholesterol leads to increased expression of LDL receptors, which in turn increases uptake and clearance of LDL-C from the blood Statins also lower very low-density lipoprotein cholesterol (VLDL-C) and triglycerides Most statins increase high-density lipoprotein cholesterol (HDL-C), but only modestly Statins also have other effects that may be direct effects of the drug or indirect effects of lowering cholesterol: they improve endothelial function, decrease platelet aggregation, and reduce inflammation Statins also decrease serum concentrations of C-reactive protein (CRP), a marker for circulating inflammatory cytokines CLINICAL STUDIES — Primary Prevention – When taken by patients with risk factors, such as high LDL-C, low HDL-C, elevated CRP, hypertension, or diabetes, but no previous coronary heart disease, statins can reduce the risk of a cardiovascular event.2 Secondary Prevention – Controlled trials in patients with cardiovascular disease have shown that lowering of LDL-C with high-intensity statin therapy (defined as reducing LDL-C by 50%) decreases the incidence of cardiac events, stroke, and coronary death significantly more than less intensive regimens Each additional mmol/L (18 mg/dL) decrease in LDL-C reduces all-cause mortality by 10% and major vascular events by 20%.3 ADVERSE EFFECTS — Statins are generally well tolerated Some patients who cannot tolerate one statin may tolerate another Muscle effects ranging from myalgia (soreness, cramps, weakness, or tenderness with or without increased serum creatine kinase [CK]) to myositis (pain and tenderness with increased CK) are common Rarely, rhabdomyolysis and myoglobinemia leading to renal failure can occur In one randomized trial (SEARCH) in 12,064 patients, the incidence of myopathy (muscle pain or weakness and a CK >10 times the upper limit of normal [ULN]) was 0.9% (53 of 6031) in  patients taking 80 mg of simvastatin daily and 0.03% (2 of 6033) in   those taking 20 mg of simvastatin daily (the maximum daily dose of simvastatin has since been lowered from 80 mg to 40 mg).4,5 A similar doserelated effect has not been reported with atorvastatin in clinical trials CK levels should be measured if the patient develops myalgia; if levels exceed 3-5 times the ULN and are unrelated to unusual or excessive exercise, most expert clinicians would lower the dose or discontinue the drug An increase in plasma aminotransferase activity to >3 times ULN occurs in 1-2% of patients taking high doses of statins such as 80 mg of atorvastatin Patients who develop mild-to-moderate transaminase elevations with one statin may be able to tolerate another statin Federal copyright law prohibits unauthorized reproduction by any means and imposes severe fines Drugs for Lipids Table Statins FDA-Approved Usual Adult Daily Dosage1 Usual Decrease in LDL Cholesterol2 Cost3 10, 20, 40, 80 mg tabs Initial: 10-20 mg once Maximum: 80 mg once 35–40% 50–60% $10.50 147.00 20, 40 mg caps Initial: 40 mg bid Maximum: 40 mg bid 20–25% 30–35% 163.20 252.60 80 mg once 35–38% 162.00 Initial: 20 mg once Maximum: 80 mg once4 Initial: 20 mg once Maximum: 60 mg once 25–30% 35–40% 20–25% 40–45% 10.80 Drug Formulations Atorvastatin – generic Lipitor (Pfizer) Fluvastatin – generic Lescol (Novartis) extended-release – Lescol XL 80 mg tabs Lovastatin – generic 10, 20, 40 mg tabs extended-release – Altoprev (Watson/Actavis) 20, 40, 60 mg tabs 463.30 Pitavastatin – Livalo (Kowa) 1, 2, mg tabs Initial: mg once Maximum: mg once 35–40% 40–45% 150.00 Pravastatin – generic Pravachol (BMS) 10, 20, 40, 80 mg tabs Initial: 40 mg once5 Maximum: 80 mg once 30–35% 35–40% 26.10 159.90 Rosuvastatin – Crestor (AstraZeneca) Simvastatin – generic Zocor (Merck) 5, 10, 20, 40 mg tabs Initial: 10-20 mg once6,7 Maximum: 40 mg once8 Initial: 10-20 mg once9 Maximum: 40 mg once10,11 45–50% 50–60% 35–40% 45–50% 171.30 5, 10, 20, 40, 80 mg tabs 4.20 186.60 Some expert clinicians use lower doses for initial treatment of patients with only modest elevations of LDL-C or a history of poor tolerance to these drugs For patients who require a large reduction in LDL-C, some would use higher doses initially Statins are generally most effective when taken in the evening Dosage adjustment may be needed for patients with renal or hepatic impairment Statins in doses that lower LDL-C by >50% are considered high-intensity therapy Those that lower LDL-C by 30-12 months without evidence of myopathy can continue at this dose 11 The maximum dose of simvastatin should be 10 mg daily in patients also taking diltiazem (Cardizem) or verapamil (Calan) and 20 mg daily if taken with amiodarone (Cordarone), amlodipine (Norvasc), or ranolazine (Ranexa) or lower doses of the same one Statin treatment is safe in patients with mild to moderate elevations of transaminase levels (≤3 times ULN) and can reduce cardiovascular morbidity and improve liver function in patients with mild fatty liver.6 A meta-analysis of 13 statin trials, each including >1000 patients, found an increased risk of diabetes mellitus in men and women treated with statins compared to placebo.7 Another meta-analysis found a higher risk of new-onset diabetes with more intensive statin therapy than with moderate-dose therapy.8 The 2013 ACC/AHA guidelines estimate that the risk of new-onset diabetes is about 0.1 cases/100 patients/year with moderateintensity statin therapy (defined as reducing LDL-C by 30-50%).1 An observational study has suggested a rare association of statin use with polyneuropathy.9 Other reports have described memory loss, sleep disturbances, erectile dysfunction, gynecomastia, a lupus-like syndrome, and acute pancreatitis, but with all of these, the causeand-effect relationship is not clear A meta-analysis of 26 randomized controlled trials, each including at least 1000 patients treated for a minimum of years, found no increase in cancer incidence or deaths due to nonvascular causes with statin therapy.3 DRUG   INTERACTIONS — Statin-induced myopathy is often caused by drug interactions Simvastatin and lovastatin undergo extensive first-pass metabolism by CYP3A4 in the liver; their plasma concentrations can be increased dramatically with concurrent use of strong CYP3A4 inhibitors.10 Atorvastatin undergoes less first-pass metabolism by CYP3A4 and most 3A4 inhibitors produce only small increases in its plasma concentrations, but rhabdomyolysis has occurred Fluvastatin is metabolized primarily by CYP2C9 Pravastatin, pitavastatin, and rosuvastatin are not metabolized by the cytochrome P450 enzymes to a clinically significant extent and are least affected by other drugs Concurrent administration of cyclosporine (Neoral, and others) increases serum concentrations of all statins and the risk of rhabdomyolysis, probably through inhibition of drug transporters such as OATP and P-glycoprotein Gemfibrozil (Lopid, and generics) also increases serum concentrations of statins, possibly Treatment Guidelines from The Medical Letter • Vol 12 (Issue 137) • January 2014 Drugs for Lipids Table Non-Statins Drug Some Available Formulations Usual Adult Daily Dosage1 Bile Acid Sequestrants Colesevelam3 – Welchol tablets (Daiichi Sankyo) Welchol packets Colestipol – generic Colestid tablets (Pfizer) Colestid packets Cholestyramine – generic (packets) generic (granules) generic light (packets) 625 mg tabs 3.75 g/packet g tabs, g packet, g/scoop g tabs g/packet, g/scoop g/packet g/scoop g/packet tabs once or tabs bid 3.75 g once or 1.875 g bid 10 g once or g bid 2-16 g once or divided g once or g bid Cost2 $325.80 325.80 120.20 60.30 192.20 123.00 66.60 123.00 Cholesterol Absorption Inhibitor Ezetimibe – Zetia (Merck) 10 mg tabs 10 mg once 163.60 600 mg tabs 600 mg bid 13.70 192.40 54, 160 mg tabs 40, 120 mg tabs 50, 150 mg caps 54, 160 mg tabs 48, 145 mg tabs 160 mg tabs 67, 134, 200 mg caps 30, 43, 90, 130 mg caps 67, 134, 200 mg caps 45, 135 mg delayed-release caps 160 mg once 120 mg once 150 mg once 160 mg once 145 mg once 160 mg once 200 mg once 130 mg once 200 mg once 135 mg once 57.00 265.80 130.10 109.50 174.90 199.80 66.20 192.30 109.50 143.90 166.70 500 mg tabs 500, 750, 1000 mg ER tabs 1000 mg tid 1000 mg once 250, 500, 750 mg SR tabs 1000 mg bid 3.74 163.50 189.40 14.50 1000 mg caps5 1000 mg caps7 1, 1.2 g caps9 caps bid6 caps once or caps bid6 caps tid 184.00 210.80 18.0010 Fibrates Gemfibrozil – generic Lopid (Pfizer) Fenofibrate – non-micronized generic3 Fenoglide (Santarus)3 Lipofen (Kowa)3 Lofibra (Gate)3 Tricor (AbbVie) Triglide (Shionogi) micronized – generic3 Antara (Lupin) Lofibra (Gate)3 Fenofibric acid – generic Trilipix (AbbVie) Niacin Niacin immediate-release – OTC extended-release4 – generic Niaspan (AbbVie) sustained-release – Slo-Niacin (Upsher-Smith) Fish Oil Capsules Vascepa (Amarin)3 Lovaza (GSK) USP-verified fish oil capsules8 Dosage adjustment may be needed for renal or hepatic impairment Approximate wholesale acquisition cost (WAC) for 30 days’ treatment with the lowest usual adult dosage Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) December 5, 2013 Reprinted with permission by FDB, Inc All rights reserved ©2013 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Should be taken with food Taken with a low-fat snack at bedtime Each 1-gram capsule contains 1000 mg EPA FDA-approved dose for treating hypertriglyceridemia (>500 mg/dL) Each 1-gram capsule contains about 465 mg EPA and 375 mg DHA (total 900 mg polyunsaturated fatty acids [PUFAs]) USP-verified fish oil products are manufactured by Berkley & Jensen, Kirkland, and Nature Made Most 1-gram capsules contain 300 mg PUFAs (180 mg EPA and 120 mg DHA); Nature Made Capsules are 1.2 g containing 360 mg PUFAs (216 mg EPA and 144 mg DHA) Three capsules are approximately equal to one Lovaza capsule 10 Cost of bottles containing 400 Nature Made capsules based on retail price at Costco.com Accessed December 10, 2013 through inhibition of drug transporters such as OATP, increasing the risk of rhabdomyolysis CHOICE OF A STATIN — Lovastatin, pravastatin, simvastatin, and atorvastatin are available generically, and all have been shown to reduce cardiovascular risk Of these, atorvastatin is the most effective in lowering LDL-C and has a well-documented beneficial effect on clinical outcomes Rosuvastatin may be slightly more effective than atorvastatin in lowering LDL-C, and has also been shown to improve clinical outcomes Pitavastatin has not been shown to decrease LDL-C more than recommended doses of other statins with longer safety records and, unlike other statins, no data are available on clinical outcomes with pitavastatin.11 CHOLESTEROL ABSORPTION INHIBITOR Ezetimibe inhibits intestinal absorption of both dietary and biliary cholesterol by blocking its transport at the brush border of the small intestine The recommended dose of 10 mg/day reduces LDL-C by about 18% A fixed-dose combination of ezetimibe plus simvastatin (Vytorin) or atorvastatin (Liptruzet) lowers LDL-C levels more than a statin alone No convincing data are available to date showing that ezetimibe alone or in combination with a statin improves cardiovascular outcomes ADVERSE EFFECTS — Ezetimibe has generally been well tolerated Diarrhea, arthralgia, rhabdomyolysis, Treatment Guidelines from The Medical Letter • Vol 12 (Issue 137) • January 2014 Drugs for Lipids hepatitis, pancreatitis, and thrombocytopenia have been reported Patients with moderate-to-severe hepatic impairment should not take ezetimibe DRUG INTERACTIONS — Ezetimibe may increase the anticoagulant effect of warfarin Bile acid sequestrants interfere with the absorption of ezetimibe; they should be taken at least several hours apart Cyclosporine increases plasma levels of ezetimibe and ezetimibe increases cyclosporine levels; the clinical significance of these effects is unknown FIBRIC ACID DERIVATIVES Fibrates activate the nuclear transcription factor PPARalpha (peroxisome proliferator-activated receptoralpha), which regulates genes that control lipid and glucose metabolism, inflammation, and endothelial function Gemfibrozil, fenofibrate, fenofibric acid, and bezafibrate (Bezalip – available in Canada, not in the US) lower triglycerides and VLDL-C, usually by 25-50%, and may increase HDL-C They may lower LDL-C, but when they decrease elevated triglycerides, LDL-C may increase Fibrates are indicated for patients with hypertriglyceridemia severe enough to be at risk for pancreatitis.12 EFFICACY — Gemfibrozil is the only fibrate with demonstrated beneficial effects on cardiovascular outcomes,13 but drug interactions with statins are a major problem with its use Fenofibrate may be more effective than gemfibrozil in lowering plasma LDL-C and triglycerides, but a randomized trial (ACCORD) in 5518 patients with type diabetes found that combination therapy with fenofibrate and simvastatin did not improve cardiovascular outcomes more than simvastatin alone.14 Fenofibric acid, the active metabolite of fenofibrate, is the only fibrate approved by the FDA for use with a statin to reduce triglyceride levels and raise HDL-C,15 but there is no evidence that it is more effective than any other fibric acid derivative in lowering triglyceride levels or increasing HDL-C and, as with other fenofibrates, addition of fenofibric acid to a statin has not been shown to improve cardiovascular outcomes.16 ADVERSE EFFECTS — Fibrates are generally well tolerated Gastrointestinal problems are the most common complaint Cholelithiasis, hepatitis, and myositis can occur Fibrates are contraindicated in patients with liver or gall bladder disease A paradoxical severe decrease in HDL-C has been reported; if this occurs, the fibrate should be stopped Aminotransferase elevations have occurred with fibrate therapy Fenofibrate can cause elevations in serum creatinine; the clinical significance of this finding is unknown DRUG INTERACTIONS — Fibrates may potentiate the effects of oral anticoagulants and oral hypoglycemic drugs Gemfibrozil can increase serum concentrations of Table Adverse Effects of Cholesterol-Lowering Drugs STATINS GI disturbances, headache, rash, fatigue, myalgia and muscle weakness leading to rhabdomyolysis, elevated hepatic enzymes, hepatic dysfunction, and increased risk of diabetes mellitus Rare: Polyneuropathy, memory loss, sleep disturbances, impotence, gynecomastia, lupus-like syndrome, and pancreatitis FIBRIC ACID DERIVATIVES GI disturbances, cholelithiasis, hepatitis, and myositis NIACIN Skin flushing, pruritus, GI disturbances, blurred vision, fatigue, glucose intolerance, hyperuricemia, hepatic toxicity, and exacerbation of peptic ulcers (adverse effects, especially flushing, are more frequent with immediate-release products) Rare: Dry eyes and hyperpigmentation EZETIMIBE Diarrhea, arthralgia, rhabdomyolysis, hepatitis, pancreatitis, and thrombocytopenia BILE ACID SEQUESTRANTS Constipation, heartburn, nausea, eructation, and bloating (adverse effects are more common with colestipol and cholestyramine and may diminish over time) FISH OIL Eructation, dyspepsia, and unpleasant aftertaste statins, possibly through inhibition of drug transporters such as OATP, increasing the risk of rhabdomyolysis Fenofibrate is eliminated renally and should be used with caution in patients taking cyclosporine or other nephrotoxic drugs NIACIN (NICOTINIC ACID) Niacin modifies all plasma lipoproteins and lipids favorably It increases HDL-C by 15-35% and decreases triglycerides by 10-50% It decreases total plasma LDL-C by 5-25%, changing small, dense LDL particles to lower-risk large, buoyant forms It also decreases plasma levels of lipoprotein(a), another marker of cardiovascular risk Niacin is available in immediateand extended-release (Niaspan) formulations Most of the data relating to reductions in cardiovascular disease with niacin comes from studies with immediate-release niacin.17 When patients received intensive therapy (4080 mg/day of simvastatin), with or without ezetimibe (10 mg/day), to lower LDL-C to the range of 40-80 mg/dL, the addition of extended-release niacin 1500-2000 mg/ day did not reduce cardiovascular and cerebrovascular clinical events.18 ADVERSE EFFECTS  —  Niacin can cause skin flushing and pruritus, gastrointestinal distress, blurred vision, fatigue, glucose intolerance, hyperuricemia, hepatic toxicity, exacerbation of peptic ulcer and, rarely, dry eyes or hyperpigmentation Some adverse effects, particularly flushing, are more common with the immediate-release formulation Cutaneous reactions can be diminished by starting with a low dose of niacin, by taking it after meals, and by taking aspirin (81-325 mg) 30 minutes before niacin BILE ACID SEQUESTRANTS The resins cholestyramine (Questran, and others) and colestipol (Colestid, and others) and the hydrophilic Treatment Guidelines from The Medical Letter • Vol 12 (Issue 137) • January 2014 Drugs for Lipids polymer colesevelam hydrochloride (Welchol) are not absorbed from the gastrointestinal tract These drugs can lower LDL-C by up to 20% and increase HDL-C, but may raise plasma triglyceride concentrations in patients with hypertriglyceridemia Cholestyramine and colestipol have been shown to reduce the number of cardiovascular events, but no clinical outcome data are available for colesevelam ADVERSE EFFECTS — Constipation occurs frequently with colestipol and cholestyramine and may be accompanied by heartburn, nausea, eructation, and bloating Colesevelam is much better tolerated DRUG INTERACTIONS — Bile acid sequestrants can interfere with the absorption of other drugs, including statins Colesevalam does not appear to interfere with the absorption of most statins FISH OIL Long-chain omega-3 polyunsaturated fatty acids (PUFAs), which are present in cold-water fish such as herring or salmon and are commercially available in capsules, can decrease fasting triglyceride concentrations 20-50% by reducing hepatic triglyceride production and increasing triglyceride clearance.19 With long-term intake, they may increase HDL-C EFFICACY — The results of recent studies not offer any convincing evidence that fish oil supplements either prevent cardiovascular disease or improve outcomes in patients who already have it.20,21 Lovaza (formerly Omacor), a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), was the first omega-3 PUFAproduct to be approved by the FDA for treatment of severe hypertriglyceridemia Daily doses of 3-12 g can lower triglycerides by 20-50%, but have not been shown to prevent pancreatitis, which is a major concern in patients with very high triglycerides Vascepa, the second FDA-approved omega-3 PUFA product for treatment of severe hypertriglyceridemia, is the ethyl ester of EPA In controlled trials, it has reduced triglyceride levels by 22-33% compared to placebo.22 ADVERSE EFFECTS — DHA can increase LDL-C levels, but EPA apparently does not Fish oil supplements are generally well tolerated Adverse effects have included eructation, dyspepsia, and an unpleasant after- taste Worsening glycemic control has been reported in diabetic patients taking large doses Fish oil in large doses can also inhibit platelet aggregation and increase bleeding time; whether it could cause clinically significant bleeding has not been established COMBINATIONS Statins can be used in combination with fenofibrate, niacin, colesevelam, or omega-3 fatty acids to lower triglycerides and increase HDL-C in addition to lowering Table Statin Combination Products* Drug Cost1 Strength Niacin ER/lovastatin Advicor (AbbVie)2 Niacin ER/simvastatin Simcor (AbbVie)3 Ezetimibe/simvastatin Vytorin (Merck)4 Ezetimibe/atorvastatin Liptruzet (Merck)5 500/20 mg 750/20 mg 1000/20 mg 1000/40 mg $153.00 164.10 176.00 203.70 500/20 mg 750/20 mg 1000/20 mg 500/40 mg 1000/40 mg 107.10 152.70 189.40 107.10 189.40 10/10 mg 10/20 mg 10/40 mg 10/80 mg 165.80 165.80 165.80 165.80 10/10 mg 10/20 mg 10/40 mg 10/80 mg 165.00 165.00 165.00 165.00 * In addition to the combinations listed in the table, some statins are also available in combination with drugs used to treat other indications Atorvastatin is available in combination with the calcium channel blocker amlodipine (Caduet, and generics) and simvastatin is available with the antidiabetic drug sitagliptin (Juvisync) Approximate wholesale acquisition cost (WAC) of 30 tablets Source: Analy$ource® Monthly (Selected from FDB MedKnowledge™) December 5, 2013 Reprinted with permission by FDB, Inc All rights reserved ©2013 www fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Usual daily dosage is 1-2 tablets Maximum daily dosage is 2000/40 mg Take with a low-fat snack at bedtime Usual daily dosage is 1000/20 mg to 2000/40 mg taken at bedtime with a low-fat snack Maximum daily dosage is 2000/40 mg Usual daily dosage is 10/10 mg to 10/40 mg in the evening Maximum daily ezetimibe dosage is 10 mg Usual daily dosage is 10/10 mg to 10/80 mg once daily LDL-C Although concurrent use of ezetimibe and a fibrate might normalize plasma lipids in patients with combined dyslipidemia, it might also cause gallbladder disease because both drugs increase biliary cholesterol excretion In severe hypertriglyceridemia not adequately controlled by diet, fibrates and niacin could be used together, possibly in combination with omega-3 PUFAs Since treatment of hypertriglyceridemia with a fibrate may increase LDL-C, it sometimes becomes necessary to add a statin as well HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA Two drugs have recently been approved for homozygous familial hypercholesterolemia (HoFH).23 This inherited condition is most commonly caused by defects in the low-density lipoprotein receptor gene, causing very high levels of LDL-C Without treatment, cardiovascular disease and death can occur in childhood The prevalence of HoFH is about one per million persons; it affects about 300 people in the US Both mipomersen (Kynamro), which must be injected subcutaneously, and lomitapide (Juxtapid), which is taken orally, can lower LDL-C in patients with HoFH already taking maximum dosages of other lipid-lowering drugs Whether either one could eliminate the need for apheresis remains to be determined Treatment Guidelines from The Medical Letter • Vol 12 (Issue 137) • January 2014 Drugs for Lipids PREGNANCY Statins are contraindicated (category X) for use during pregnancy; congenital anomalies have been reported with lovastatin in some animal species and in a few human infants Gemfibrozil and fenofibrate are classified as category C (risk cannot be ruled out) for use during pregnancy and are teratogenic in animals Cholestyramine and colestipol might interfere with absorption of important nutrients Colesevelam appears to be safe in animal reproductive studies Ezetimibe has caused skeletal defects in some animal studies and is classified as category C for use during pregnancy Niacin and the omega-3 PUFAs are also classified as category C for use during pregnancy 10 11 12 13 14 15 16 17 18 19 20 21 22 23 NJ Stone et al 2013 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 J Am Coll Cardiol 2013 November (epub) PM Ridker and PW Wilson A trial-based approach to statin guidelines JAMA 2013; 310:1123 Cholesterol Treatment Trialists’ (CTT) Collaboration Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials Lancet 2010; 376:1670 SEARCH Collaborative Group Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial Lancet 2010; 376:1658 FDA drug safety communication: new restrictions, contraindications, and dose limitations to Zocor (simvastatin) to reduce the risk of muscle injury Available at www.fda.gov/drugs/drugsafety/ucm256581.htm Accessed December 4, 2013 MJ Tikkanen et al Effect of intensive lipid lowering with atorvastatin on cardiovascular outcomes in coronary heart disease patients with mild-tomoderate baseline elevations in alanine aminotransferase levels Int J Cardiol 2013; 168:3846 N Sattar et al Statins and risk of incident diabetes: a collaborative metaanalysis of randomised statin trials Lancet 2010; 375:735 D Preiss et al Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis JAMA 2011; 305:2556 D Gaist et al Statins and risk of polyneuropathy: a case-control study Neurology 2002; 58:1333 Inhibitors and inducers of CYP enzymes and P-glycoprotein Med Lett Drugs Ther 2013; 55:e44 Pitavastatin (Livalo) – the seventh statin Med Lett Drugs Ther 2010; 52:57 Drugs for hypertriglyceridemia Med Lett Drugs Ther 2013; 55:17 L Tenkanen et al Gemfibrozil in the treatment of dyslipidemia: an 18year mortality follow-up of the Helsinki Heart Study Arch Intern Med 2006; 166:743 ACCORD Study Group Effects of combination lipid therapy in type diabetes mellitus N Engl J Med 2010; 362:1563 Fenofibric acid (Trilipix) Med Lett Drugs Ther 2009; 51:33 AB Goldfine et al Fibrates in the treatment of dyslipidemias – time for a reassessment N Engl J Med 2011; 365:481 E Bruckert et al Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis Atherosclerosis 2010; 210:353 What about niacin? Med Lett Drugs Ther 2011; 53:93 Fish oil supplements Med Lett Drugs Ther 2012; 54:83 Risk and Prevention Study Collaborative Group N-3 fatty acids in patients with multiple cardiovascular risk factors N Engl J Med 2013; 368:1800 SM Kwak et al Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials Arch Intern Med 2012; 172:686 Icosapent ethyl (Vascepa) for severe hypertriglyceridemia Med Lett Drugs Ther 2013; 55:33 Two new drugs for homozygous familial hypercholesterolemia Med Lett Drugs Ther 2013; 55:25 Coming Soon in Treatment Guidelines: Drugs for HIV Infection – February 2014 Drugs for Atrial Fibrillation – March 2014 Follow us on Twitter @MedicalLetter Treatment Guidelines from The Medical Letter® EDITOR IN CHIEF: Mark Abramowicz, M.D EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School 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Call us at 800-211-2769 or 914-235-0500 or e-mail us at: custserv@medicalletter.org Questions start on next page Treatment Guidelines from The Medical Letter • Vol 12 (Issue 137) • January 2014 DO NOT FAX OR MAIL THIS EXAM To take CME exams and earn credit, go to: medicalletter.org/CMEstatus Issue 137 Questions Which one of the following would be the best choice for treatment of patients with atherosclerotic cardiovascular disease? a colesevelam b ezetimibe c niacin d atorvastatin A 68-year-old man has been taking 200 mg of amiodarone and 40 mg of simvastatin daily for several months He complains of muscle pain and is concerned that the soreness and tenderness in his muscles is getting worse Which of the following would you recommend? a reducing the dose of simvastatin to 20 mg b increasing the dose of amiodarone to 400 mg c increasing the dose of simvastatin to 60 mg d continuing both drugs as originally prescribed Adverse effects of statins include: a myopathy b polyneuropathy c new-onset diabetes d all of the above In recommended doses, ezetimibe reduces LDL-C by about: a 30% b 10% c 18% d 40% A 72-year-old woman with low HDL-C levels and hypertriglyceridemia severe enough to be at risk for pancreatitis asks her physician to recommend a lipid-regulating drug Which of the following would be the best choice for this patient? a pitavastatin b niacin c fenofibric acid d ezetimibe Which of the following statins are available generically and have been shown to reduce cardiovascular risk? a atorvastatin b lovastatin c pravastatin d all of the above Adverse effects of niacin include: a skin flushing b blurred vision c fatigue d all of the above Which of the following drugs has not been shown to improve cardiovascular outcomes when taken in combination with a statin? a ezetimibe b fenofibric acid c niacin d all of the above Which of the following drugs can decrease fasting triglyceride concentrations by 20-50%? a Lovaza b cholestyramine c colestipol d Juxtapid 10 Adverse effects of fish oil supplements include: a eructation b dyspepsia c an unpleasant aftertaste d all of the above 11 Mipomersen and lomitapide have recently been approved for treatment of: a homozygous familial hypercholesterolemia b hypertriglyceridemia c myopathy associated with use of statins d all of the above 12 Which of the following drugs is contraindicated (category X) for use during pregnancy? a ezetimibe b niacin c simvastatin d gemfibrozil ACPE UPN: 0379-0000-14-137-H01-P; Release: December 2013, Expire: December 2014 Treatment Guidelines from The Medical Letter • Vol 12 (Issue 137) • January 2014 ... lipid-lowering drugs Whether either one could eliminate the need for apheresis remains to be determined Treatment Guidelines from The Medical Letter • Vol 12 (Issue 137) • January 2014 Drugs for Lipids. .. and P-glycoprotein Med Lett Drugs Ther 2013; 55:e44 Pitavastatin (Livalo) – the seventh statin Med Lett Drugs Ther 2010; 52:57 Drugs for hypertriglyceridemia Med Lett Drugs Ther 2013; 55:17 L Tenkanen... 172:686 Icosapent ethyl (Vascepa) for severe hypertriglyceridemia Med Lett Drugs Ther 2013; 55:33 Two new drugs for homozygous familial hypercholesterolemia Med Lett Drugs Ther 2013; 55:25 Coming