The medical letter on drugs and therapeutics october 24 2016

The Medical Letter ® on Drugs and Therapeutics Volume 58 ISSUE ISSUE No 1433 1506 Volume 56 October 24, 2016 IN THIS ISSUE Lipid-Lowering Drugs p 133 In Brief: Hepatitis B Reactivation with Direct-Acting Antiviral Drugs for Hepatitis C p 140 Important Copyright Message FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter, Inc publications are protected by U.S 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 U.S 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 Published by The Medical Letter, Inc • A Nonprofit Organization 5HYLVHG6HHSDJH 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 The Medical Letter ® on Drugs and Therapeutics Volume 58 October 24, 2016 Take CME Exams ISSUE ISSUE No 1433 1506 ALSO IN THIS ISSUE In Brief: Hepatitis B Reactivation with Direct-Acting Antiviral Drugs for Hepatitis C p 140 Volume 56 ▶ Lipid-Lowering Drugs Note: An addendum to this article has been published Lipid-lowering drugs should be taken indefinitely; when they are stopped, plasma lipoproteins return to pretreatment levels HMG-CoA reductase inhibitors (statins) remain the drugs of choice for treatment of most patients who require lipid-lowering therapy STATINS — Statins block the rate-limiting step in cholesterol synthesis The subsequent reduction in hepatic cholesterol causes upregulation of lowdensity lipoprotein (LDL) receptors, increasing uptake and clearance of LDL-cholesterol (LDL-C) from the blood Statins also decrease very low-density lipoprotein cholesterol (VLDL-C) and triglyceride levels and modestly increase high-density lipoprotein cholesterol (HDL-C) levels Other direct effects of statins or indirect effects of lowering cholesterol include improved endothelial function, decreased platelet aggregation, and reduced inflammation Statins also decrease serum concentrations of C-reactive protein, a marker of inflammation Efficacy – Taken as an adjunct to diet modification, increased exercise, and smoking cessation, statins can reduce the risk of first cardiovascular events and death (primary prevention) in patients at high risk for atherosclerotic cardiovascular disease.1-4 Even in patients at lower risk for cardiovascular disease, treatment with a statin can significantly reduce the incidence of cardiovascular events.5 Controlled trials in patients with cardiovascular disease (secondary prevention) have shown that high-intensity statin therapy (defined as reducing LDL-C by ≥50% on average) decreases the incidence of cardiac events, stroke, and coronary death significantly more than less intensive regimens In one meta-analysis, each additional mmol/L (39 mg/dL) reduction in LDL-C was associated with a 20% reduction in major vascular events and a 10% reduction in all-cause mortality.6 Choice of a Lipid-Lowering Drug ▶ ▶ ▶ ▶ ▶ ▶ ▶ ▶ Statins are the lipid-lowering drugs of choice for treatment and prevention of cardiovascular disease in most patients Statins can decrease the incidence of major coronary events and death in patients with atherosclerotic cardiovascular disease Statins can also reduce the risk of a first cardiovascular event and death in patients with risk factors such as elevated levels of low-density lipoprotein cholesterol (LDL-C) or diabetes when taken as an adjunct to diet modification, increased exercise, and smoking cessation Addition of ezetimibe to high-dose simvastatin can reduce the incidence of secondary cardiovascular events Combining a statin with a PCSK9 inhibitor can reduce LDL-C levels much more than a statin alone, but to date no studies are available demonstrating that such combinations improve clinical outcomes Limited evidence suggests that use of a bile acid sequestrant alone or in combination with a statin may reduce the incidence of cardiovascular events Addition of niacin or a fibrate to a statin has not been shown to reduce cardiovascular risk and is no longer recommended There is no convincing evidence that use of fish oil supplements prevents cardiovascular disease or improves outcomes in patients who already have it Combining a statin with another LDL-C lowering drug such as ezetimibe may reduce the incidence of cardiovascular events more than a statin alone.7 Adverse Effects – Statins are generally well tolerated.8 Some patients who cannot tolerate one statin may tolerate another Muscle pain and weakness with or without increased creatine kinase (CK) levels are commonly reported in patients taking statins in clinical practice, but in some randomized trials, muscle symptoms were reported just as often in patients taking placebo.9 Rarely, rhabdomyolysis and myoglobinemia leading to renal failure can occur In one randomized trial (SEARCH) in 12,064 patients, the incidence of myopathy with a CK level >10 times the upper limit of normal (ULN) was 0.9% (53 of 6031) in  patients taking simvastatin 80 mg daily and 0.03% (2 of 6033) in those taking 133 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter ® October 24, 2016 Vol 58 (1506) Table Lipid-Lowering Drugs Drug Statins Atorvastatin – generic Lipitor (Pfizer) Fluvastatin – generic Lescol (Novartis) extended-release – generic Lescol XL Lovastatin – generic Formulations Usual Adult Dosage1 Average LDL-C Reduction2 10, 20, 40, 80 mg tabs Initial: 10-20 mg once/d Maximum: 80 mg once/d Initial: 40 mg bid Maximum: 40 mg bid Maximum: 80 mg once/d 35-40% 50-60% 20-25% 30-35% 35-38% extended-release – Altoprev (Watson/Actavis) Pitavastatin – Livalo (Kowa) 20, 40, 60 mg tabs Initial: 20 mg once/d Maximum: 80 mg once/d4 Initial: 20 mg once/d Maximum: 60 mg once/d Initial: mg once/d Maximum: mg once/d Initial: 40 mg once/d5 Maximum: 80 mg once/d Initial: 10-20 mg once/d6,7 Maximum: 40 mg once/d8 Initial: 10-20 mg once/d9 Maximum: 40 mg once/d10,11 25-30% 35-40% 20-25% 40-45% 35-40% 40-45% 30-35% 35-40% 45-50% 50-60% 35-40% 45-50% 10 mg once/d 15-25% 285.60 Initial: 10/10-10/20 mg once/d Maximum: 10/40 mg once/d10 40-50% 50-60% 282.90 Initial: 75 mg SC q2 wks Maximum: 150 mg SC q2 wks Initial: 140 mg SC q2 wks or 420 mg SC once/month15 Maximum: 420 mg SC once/month 45-50%13 50-60%13 55-60%13 20, 40 mg caps 80 mg tabs 10, 20, 40 mg tabs 1, 2, mg tabs Pravastatin – generic 10, 20, 40, 80 mg tabs Pravachol (BMS) Rosuvastatin – generic 5, 10, 20, 40 mg tabs Crestor (AstraZeneca) Simvastatin – generic 5, 10, 20, 40, 80 mg tabs Zocor (Merck) Cholesterol Absorption Inhibitor Ezetimibe12 – Zetia (Merck) 10 mg tabs Cholesterol Absorption Inhibitor/Statin Combination Ezetimibe/simvastatin – 10/10, 10/20, 10/40, 10/80 mg tabs Vytorin (Merck) PCSK9 Inhibitors 75, 150 mg/mL single-use pens, Alirocumab – Praluent (Sanofi/Regeneron) prefilled syringes Evolocumab – Repatha 140 mg/mL single-use (Amgen) prefilled syringes Repatha Sureclick 140 mg/mL single-use autoinjectors Repatha Pushtronex 420 mg/3.5 mL single-use infusor with prefilled cartridge 10 11 12 13 14 15 $8.60 228.40 210.70 305.50 199.50 282.20 9.50 703.20 223.50 20.70 169.70 37.20 248.50 3.40 130.80 1120.0014 1084.6014 1084.6014 1175.0014 FDA-approved dosage 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 The listed ranges correspond to the initial and maximum dosages Statin dosages that lower LDL-C by ≥50% are considered high-intensity therapy Those that lower LDL-C by 30-3 times the ULN occurs in 1-2% of patients taking high doses of a statin Patients who develop transaminase elevations with one statin may be able to tolerate lower doses of the same statin or another statin Statin treatment is safe in patients with mild to moderate transaminase elevations (≤3 times ULN) and may reduce cardiovascular morbidity even more in these patients than in those with normal transaminase levels.12 The Medical Letter ® Vol 58 (1506) October 24, 2016 Table Lipid-Lowering Drugs (continued) Drug Bile Acid Sequestrants Colesevelam16 – Welchol tablets (Daiichi Sankyo) Welchol packets Colestipol – generic Colestid tablets (Pfizer) Colestid packets Cholestyramine – packets – generic Questran (Par) granules – generic Questran packets (light)18 – generic Prevalite (Upsher Smith) Fibrates Gemfibrozil – generic Lopid (Pfizer) Fenofibrate – non-micronized generic16 Fenoglide (Santarus)16 Lipofen (Kowa)16 Lofibra (Gate)16 Tricor (AbbVie) Triglide (Shionogi) micronized – generic16 Antara (Lupin) Lofibra (Gate)16 Fenofibric acid – generic Fibricor (Tribute) delayed-release – generic Trilipix (AbbVie) Niacin Niacin immediate-release – OTC extended-release20 – generic Niaspan (AbbVie) sustained-release – Slo-Niacin (Upsher-Smith) Formulations Usual Adult Dosage1 625 mg tabs 3750 mg once/d or 1875 mg bid 3.75 g once/d or 1.875 g bid 10 g once/d or g bid 2-16 g once/d or divided 3.75 g packets g tabs; g packets; g/scoop g tabs g packets; g/scoop g packets g once/d or g bid Average LDL-C Reduction2 Cost3 15-20% $565.20 15-20% 15-20% g/scoop g packets 600 mg tabs 600 mg bid 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, 90 mg caps 67, 134, 200 mg caps 35, 105 mg tabs 160 mg once/d 120 mg once/d 150 mg once/d 160 mg once/d 145 mg once/d 160 mg once/d 200 mg once/d 90 mg once/d 200 mg once/d 105 mg once/d 45, 135 mg delayed-release caps 135 mg once/d 500 mg tabs 500, 750, 1000 mg ER tabs 1000 mg tid 1000 mg once/d 250, 500, 750 mg SR tabs 1000 mg bid 1000 mg caps21 1000 mg caps23 2000 mg bid22 4000 mg once/d or 2000 mg bid22 4-4.8 g tid 5-10%19 5-10%19 5-10%19 565.20 188.7017 96.50 307.4017 63.80 341.20 66.60 94.90 123.00 63.80 11.60 307.70 62.60 964.40 222.90 139.00 31.00 259.70 82.40 507.90 241.40 24.00 123.90 241.40 5-25% 11.20 117.50 274.20 14.60 Fish Oil Icosapent ethyl – Vascepa (Amarin)16 Omega-3 acid ethyl esters – generic Lovaza (GSK) USP-verified fish oil capsules24 1, 1.2 g caps25 0-5%19 234.00 180.00 290.00 35.0026 16 17 18 19 20 21 22 23 24 25 Should be taken with food Cost of 60 packets Contains aspartame instead of sucrose LDL-C may increase when triglyceride levels are decreased Should be taken with a low-fat snack at bedtime Each 1000-mg capsule contains 1000 mg EPA FDA-approved dose for treating hypertriglyceridemia (≥500 mg/dL) Each 1000-mg 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 1.2-g capsules contain 360 mg PUFAs (216 mg EPA and 144 mg DHA); three capsules are approximately equal to one Lovaza capsule 26 Cost of bottles containing 400 Nature Made capsules based on retail price at Costco.com Accessed October 13, 2016 In a meta-analysis of 13 trials including a total of 91,140 patients, the risk of new-onset diabetes mellitus was slightly higher with statin therapy compared to placebo.13 In another meta-analysis, the risk of newonset diabetes was higher with more intensive statin therapy than with moderate-dose therapy.14 ACC/AHA guidelines estimate that the risk of new-onset diabetes is about 0.1 cases/100 patient-years with moderateintensity statin therapy (defined as reducing LDL-C by 30-10% Initiate low- to moderate-intensity statin therapy3 7.5-10% Selectively offer low- to moderateintensity statin therapy3,4 Any Evidence insufficient to recommend initiating statin therapy >75 years Dyslipidemia, diabetes, hypertension, or smoking Calculated using the ACC/AHA Pooled Cohort Equation (tools.acc.org/ ASCVD-Risk-Estimator) Low-intensity statin therapy lowers LDL-cholesterol