Non-Statin Lipid-Lowering Agents

Transcription

1 This Clinical Resource gives subscribers additional insight related to the Recommendations published in September 2018 ~ Resource # non Non- Lipid-Lowering Agents s are the lipid-lowering agents of choice because they have by far the most, and most robust, evidence for reducing cardiovascular events, including death. 39,49 Non-statins are no longer recommended for routine use. 39,49 When deciding to start or continue a non-statin, consider the following: The addition of a non-statin to a statin has not been proven to further reduce cardiovascular mortality. 1,30,49,61 Despite IMPROVE-IT, the FDA denied the expanded indication for morbidity and mortality benefits for ezetimibe. 65 Adding a fibrate or niacin to achieve a specific LDL goal could result in reduction of the statin to a suboptimal dose. 49 Reinforce statin adherence and lifestyle changes, and check for secondary causes of LDL elevation before adding a non-statin. 49 For patients who cannot tolerate the recommended statin dose or who do not achieve the expected statin response (e.g., 50% LDL reduction with high-intensity statin) and are high-risk at baseline, consider adding a non-statin. 39,49 Consider adding ezetimibe to a statin in high-risk patients, especially those with a recent ACS. 30 Per Canadian guidelines, ezetimibe is the preferred add-on for most patients not meeting lipid goals with a statin. 39 There s no proof that adding other non-statins (fibrates, etc) to a statin improves outcomes, and niacin worsens glycemic control. 1,32,39 Consider evolocumab with maximally tolerated statin for HoFH, HeFH, or clinical CVD requiring additional LDL reduction. 53,54,61 Alirocumab is indicated for use with maximally-tolerated statin for HeFH or clinical CVD, for additional LDL reduction. 52,67 In CVD, evolocumab reduces the risk of MI, stroke, and need for revascularization. 61,54 Per Canadian guidelines, PCSK9 inhibitors are also second-line statin add-ons for AAA, diabetes, or CKD. 39 Consider a bile acid sequestrant, gemfibrozil, or niacin for patients who cannot tolerate a statin. 1,7,21,24 Do not add gemfibrozil to a statin due to myopathy risk. 49 It is reasonable to use omega-3 fatty acids, fenofibrate, or niacin for TG 500 mg/dl (~5 mmol/l) to prevent pancreatitis (with lifestyle changes). 38 TG-lowering effects of niacin, omega-3-ethyl esters, and fibrates is greatest in patients with higher baseline TG levels Canada: subgroup analysis suggests that fibrates (e.g., bezafibrate, fenofibrate, gemfibrozil) might benefit patients with high triglycerides and low HDL. 39 The chart below provides lipid effects, outcomes, and cost information for the non-statins. Information in the chart may differ from product labeling. Abbreviations: AAA = abdominal aortic aneurysm; ACS = acute coronary syndrome; CKD = chronic kidney disease; CV = cardiovascular; CVD = cardiovascular disease; ER = extended release; GI = gastrointestinal; HDL = high-density lipoprotein; HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hypercholesterolemia; IR = immediate release; LDL = low-density lipoprotein; MI = myocardial infarction; PCSK9 = proprotein convertase subtilisin/kexin type 9; SR = sustained release; subcut = subcutaneous; TG = triglycerides. PharmacistsLetter.com ~ PrescribersLetter.com ~ PharmacyTechniciansLetter.com ~ NursesLetter.com

2 (Clinical Resource #340933: Page 2 of 10) Alirocumab (Praluent) (PCSK9 inhibitor) 75 mg/two weeks: U.S.: ~$1,100 Canada: ~$ mg/two weeks: LDL : ~45% to 48%. 52,56,63 (When added to a statin.) in See column. Post-hoc analysis suggests alirocumab in combination with maximally tolerated statin doses may reduce major CV events in high-risk patients. Further data are needed to confirm [Level B-1]. 55 Very expensive. Consider with maximally tolerated statin for HeFH or clinical CVD requiring additional LDL reduction. 52,67 Canadian guidelines: second-line statin add-on option for AAA, diabetes, or CKD. 39 No dose adjustment needed with mild to moderate renal or hepatic impairment. No safety data available with severe renal or hepatic impairment. 52,67 Administer via subcut injection. 52,67 No long-term safety data. Bezafibrate (Bezalip SR, generic); (Canada only) (Fibric acid) 400 mg/day: Canada: ~$ mg/day: 35,36 LDL : 6% to 21%. HDL : 15% to 25%. TG : 25.1% to 42%. 400 mg/day: %. 21.6%. 31.7%. Secondary prevention: prevents composite endpoint of MI and sudden death in a subgroup with TG 200 mg/dl (~2.3 mmol/l) or higher. No increase in non- CV death. 37 Reversible increase in serum creatinine. 33 Requires renal dose adjustment. 33,b Limited data with statins. Cholestyramine (Questran, Questran Light [U.S.; generics only], Olestyr, generics [Canada] Continued LDL : 62 9% (4 to 8 g/day); 21% (16 to 20 g/day); 23% to 28% (>20 g/day). 4,5 ~10% (8 g/day); ~20% (24 g/day). 3,4 0% to 10%. Primary prevention, men: reduces need for bypass, and combined endpoint of coronary heart disease, death, and nonfatal MI (NNT = 59 for 7 years) [Level A-1]. 6,14 Can be difficult to tolerate due to GI side effects such as constipation and gas. 8 Canadian guidelines: statin addon option in patients not meeting lipid goals (ezetimibe preferred in

3 (Clinical Resource #340933: Page 3 of 10) Cholestyramine, continued (Bile acid sequestrant) 16 g/day: U.S.: ~$245 (packets) Canada: ~$68 HDL : 4% to 8% (16 to 24 g/day). 62 TG : 11% to 28% (4 to 24 g/day). 62 in Secondary prevention, men: with diet, reduces cardiac events vs usual care (not placebo-controlled; events not a primary outcome) [Level B-1]. 7 Slows progression and increases regression of atherosclerosis. 7,34 primary prevention, clinical CVD, diabetes, AAA, or CKD). 39 Colesevelam (Welchol, generic [U.S.], Lodalis [Canada]) (Bile acid sequestrant) 3.8 g/day: U.S.: ~$450 (tablets) Canada: ~$ g/day: LDL : 15% to 19.1%. 2,8 HDL : 3% to 8.1%. 2,8 TG : 10% (about 20% when used with insulin or sulfonylureas) g/day: 2 10% to 16%. 3% to 7%. None. Limited data with statins. Studied in combination with atorvastatin, lovastatin, pravastatin, and simvastatin. 2,10 Canadian guidelines: statin addon option in patients not meeting lipid goals (ezetimibe preferred in primary prevention, clinical CVD, AAA, diabetes, or CKD). 39 Potential lower risk of GI side effects compared to cholestyramine and colestipol. 8,64 FDA-approved for glycemic control in type 2 diabetes. 2 Colestipol (Colestid, generic [U.S.]) (Bile acid sequestrant) 10 g/day: U.S.: ~$190 (packets) Canada: ~$74 LDL : 5% (2 g/day) to 26% (16 g/day). 62 HDL: no effect. 62 TG : 10% to 15% (2 to 16 g/day) % (5 g/day) to 12% (10 g/day). 11 Reduces progression of atherosclerosis and events when combined with niacin or lovastatin (events not a primary outcome). 50 Can be difficult to tolerate due to GI side effects such as constipation and gas. 8 Canada: statin add-on option in patients not meeting lipid goals (ezetimibe preferred in primary prevention, clinical CVD, diabetes, AAA, or CKD). 39

4 (Clinical Resource #340933: Page 4 of 10) Evolocumab (Repatha) (PCSK9 inhibitor) 140 mg every two weeks: U.S.: ~$1,100 Canada: ~$540 Ezetimibe (Zetia, generics [U.S.], Ezetrol, generics [Canada]) (Cholesterol absorption inhibitor) 10 mg/day: U.S.: ~$13 Canada: ~$ mg every two weeks: 58,59,61,63 LDL : 42% to 65%. (Regardless of statin use.) 10 mg/day: 12,13 LDL : 18%. HDL : 1%. TG : 8%. in See column. 25%. 13 3% %. 13 Lowered LDL 34% to 38.5% more compared to ezetimibe. 58,60 Added to a high- or moderate-dose statin, prevents one CV death, MI, or stroke for every 67 highrisk CVD patients treated for about two years (FOURIER study). CV death as a standalone outcome not affected. Most patients had a prior MI, and about one third had diabetes and/or smoked. 61 With simvastatin 20 mg, reduces first major atherosclerotic event in chronic renal disease [Level A-1]. 29 Adding ezetimibe to simvastatin 40 mg post-acs prevents one CV event for every 50 patients treated for 7 yrs vs simvastatin alone [Level A-1]. 30 Very expensive. Consider with maximally tolerated statin for HoFH, HeFH, or clinical CVD requiring additional LDL reduction. 53,54,61 Canada: second-line statin addon option for AAA, diabetes, or CKD. 39 Administer by subcut injection. 53,54 No dosage adjustment needed with mild to moderate hepatic impairment. No data in severe hepatic impairment. 53,54 Canada: caution in severe hepatic impairment. Use in severe renal impairment is not recommended 53 No long-term safety data. Consider as a moderate-dose statin add-on for high-risk secondary prevention patients who can t tolerate a high-intensity statin, or who don t get the expected 50% LDL reduction with a high-intensity statin. 49 Canada: preferred statin add-on for primary prevention, AAA, diabetes, clinical CVD, or CKD. A statin-add-on option in genetic dyslipidemia. 39 U.S.: ezetimibe/simvastatin [Vytorin, generics]). ~$100 [10 mg/20 mg/day]).

5 (Clinical Resource #340933: Page 5 of 10) Fenofibrate U.S.: Antara, generics; Fenoglide, generics; Fibricor; Lipofen; Lofibra (generic only); Tricor, generic; Triglide; Trilipix, generics Canada: Lipidil EZ, generics; Lipidil Supra, generics (Fibric acid) U.S.: ~$105 (130 mg/day) 145 mg/day: U.S.: ~$56 Canada: ~$ mg/day: 15 LDL : 20.6%. HDL : 11% TG : 23.5% to 54.5% (greatest drop in patients with highest triglycerides). in 200 mg/day: % to 6%. 13% to 17%. 20% to 32%. Prevention of CV events in type 2 diabetes: did not reduce primary composite outcome (non-fatal MI or CV death). Improved outcomes included non-fatal MI (24% ), coronary revascularization (21% ), progression to albuminuria, and reduced laser treatments for retinopathy. Nonsignificant increase in CV death. 31 As statin add-on, did not lower risk of non-fatal MI, non-fatal stroke, or CV death more than statin alone in patients with type 2 diabetes at high risk for CV disease. 32 Option for TG 500 mg/dl (~5 mmol/l). 38 Consider for patients with high CV risk and high TG/low HDL despite statin. 39 Requires renal dose adjustment. 33,b Associated with reversible increase in serum creatinine. 33 Unclear risk of cholelithiasis. 51 In the U.S., FDA indication for fenofibric acid (Trilipix) use with statins revoked in April 2016 due to lack of CV benefit. 57 Fenofibrate is still indicated as adjunct to diet to improve lipids. 66 Preferred over gemfibrozil for use with statins for safety. 33 Canada: ~$10 (200 mg/day) Gemfibrozil (Lopid [U.S.], generics) (Fibric acid) 1,200 mg/day: U.S.: ~$16 Canada: ~$60 1,200 mg/day: LDL: No effect. 21 HDL : 6%. 21 TG : 33% to 50%. 21,41 41%. 19 9%. 19 Primary prevention, men: reduced sudden cardiac death plus fatal/nonfatal MI (NNT = 71 over 5 years) [Level A-1]. 20 Secondary prevention of nonfatal MI plus cardiac death in men with low HDL (NNT = 23 over 5 years) [Level A-1]. 21 Option for TG 500 mg/dl (~5 mmol/l). 38 Requires renal dose adjustment. 33,b Avoid with statin. 33 No mortality benefit. 20,21 Unclear risk of cholelithiasis. 51

6 (Clinical Resource #340933: Page 6 of 10) Icosapent ethyl (Vascepa) (U.S. only) (EPA; about 1 g omega-3s/capsule) 4 g/day: 46 LDL: No effect. HDL: No effect. TG : 27%. in 10.1% (2 g/day), 21.5% (4 g/day) % (4 g/day). 47 A study is underway to look at reduction in CV events with icosapent in patients taking a statin. 48 Option for TG 500 mg/dl (~5 mmol/l). 46 Safe for use with statin. 47 Use caution with fish or shellfish allergy. 46 U.S.: ~$280 (4 g/day) Niacin (Niacor [IR; U.S. only], Niaspan, generics [U.S.], Niaspan FCT [Canada]) Niacin 1 g/day: U.S.: ~$180 (Niacor) U.S.: ~$115 (Niaspan) Canada: ~$90 (Niaspan FCT) Monotherapy at usual doses: 38 TG : 20% to 50%. Niaspan 2 g/day: 23,24 LDL : 14% to 17%. HDL : 22% to 26%. Niacin IR or Niaspan 1.5 g/day: LDL : 12%. 28 HDL : 17% (Niacin IR). 28 HDL : 19% to 22% (Niaspan). 23,24 8% (Niaspan 1 g/day); 31% (Niaspan 2 g/day). 9 23% (Niaspan 1 g/day); 27% (Niaspan 2 g/day). 9 24% (Niaspan 1 g/day); 27% (Niaspan 2 g/day). 9 As statin add-on, reduces carotid intima-media thickness (surrogate marker) as compared to ezetimibe as statin add-on in patients with lower HDL. 29 Secondary MI prevention: one less MI for every 30 patients treated for five years (Coronary Drug Project) [Level B-1]. 24 No CV event benefit from combo of niacin + statin vs statin alone in patients with well-controlled LDL, low HDL, and high TG. 40 Option for TG 500 mg/dl (~5 mmol/l). 38 Raises HDL more than any other agent. Dose-dependent risk of hyperglycemia (especially in patients with type 2 diabetes) and liver toxicity. 24 No mortality benefit. 24 May increase risk of statin myopathy. 24 FDA indication for niacin ER use with statins revoked in April 2016 due to lack of CV benefit/safety. 57 In Canada, niacin is still indicated as monotherapy for dyslipidemia. 23 In the U.S., niacin is indicated as monotherapy or for use with bile acid sequestrants. 22,24

7 (Clinical Resource #340933: Page 7 of 10) Omega-3 ethyl esters (Lovaza, generics) (U.S. only) (EPA/DHA; about 1 g omega-3s/capsule). U.S.: ~$185 (4 g/day) 4 g/day: 27 LDL : 44.5%. HDL : 9.1%. TG : 45%. in 4 g/day: 25 LDL : 0.7%. 3.4%. 29.5%. Secondary prevention: reduces cardiovascular death, sudden death, and combined endpoint of death, non-fatal MI, and non-fatal stroke [Level B-1]. 26 Secondary prevention in patients with, or at risk for, type 2 diabetes: did not reduce CV events. About half of patients were taking a statin. 42 Option for TG 500 mg/dl (~5 mmol/l). 38 Safe for use with statin. 25 Associated with an increase in risk for recurrence of symptomatic atrial fibrillation or flutter, especially within first three months of therapy. 27 Use with caution with fish or shellfish allergy. 27 a. U.S. cost is wholesale acquisition cost. Medication pricing by Elsevier, accessed March Canadian cost is wholesale. Cost is for generic, if available, of dose specified. b. Maximum daily dose if CrCl <60 ml/min: bezafibrate 200 mg, gemfibrozil 600 mg, and fenofibrate 67 mg. Avoid if CrCl <15 ml/min. 33 Users of this resource are cautioned to use their own professional judgment and consult any other necessary or appropriate sources prior to making clinical judgments based on the content of this document. Our editors have researched the information with input from experts, government agencies, and national organizations. Information and internet links in this article were current as of the date of publication.

8 (Clinical Resource #340933: Page 8 of 10) Levels of Evidence In accordance with our goal of providing Evidence- Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish. Level Definition Study Quality A B C Good-quality patient-oriented evidence.* Inconsistent or limited-quality patient-oriented evidence.* 1. High-quality RCT 2. SR/Meta-analysis of RCTs with consistent findings 3. All-or-none study 1. Lower-quality RCT 2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings 3. Cohort study 4. Case control study Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening. *Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life). RCT = randomized controlled trial; SR = systematic review [Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69: Project Leader in preparation of this clinical resource (340933): Melanie Cupp, Pharm.D., BCPS References 1. Clinical Resource, Ezetimibe s Role in Cardiovascular Risk Reduction. Pharmacist s Letter/Prescriber s Letter. January Product information for Welchol. Daiichi Sankyo. Parsippany, NJ July Comparative efficacy and safety of pravastatin and cholestyramine alone and combined in patients with hypercholesterolemia. Pravastatin Multicenter Study Group II. Arch Intern Med 1993;153: Pan HY, DeVault AR, Swites BJ, et al. Pharmacokinetics and pharmacodynamics of pravastatin alone and with cholestyramine in hypercholesterolemia. Clin Pharmacol Ther 1990;48: Sprecher DL, Abrams J, Allen JW, et al. Low-dose combined therapy with fluvastatin and cholestyramine in hyperlipidemic patients. Ann Intern Med 1994;120: Rifkind BM. Lipid Research Clinics Coronary Primary Prevention Trial: results and implications. Am J Cardiol 1984;54:30C-34C. 7. Watts GF, Lewis B, Brunt JN, et al. Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St. Thomas Atherosclerosis Regression Study (STARS). Lancet 1992;339: Davidson MH, Dillon MA, Gordon B, et al. Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects. Arch Intern Med 1999;159: Wolfe ML, Vartanian SF, Ross JL, et al. Safety and effectiveness of Niaspan when added sequentially to a statin for treatment of dyslipidemia. Am J Cardiol 2001;87: Bays HE, Davidson M, Jones MR, Abby SL. Effects of colesevelam hydrochloride on low-density lipoprotein cholesterol and high-sensitivity C-reactive protein when added to statins in patients with hypercholesterolemia. Am J Cardiol 2006;97: Simons LA, Simons J, Parfitt A. Successful management of primary hypercholesterolaemia with simvastatin and low-dose colestipol. Med J Aust 1992;157: Product monograph for Ezetrol. Merck Canada. Kirkland, QC H9H 4M7. March Product information for Zetia. Merck/Schering- Plough Pharmaceuticals. North Wales, PA August Probstfield JL, Rifkind BM. The Lipid Research Clinics Coronary Primary Prevention Trial: design, results, and implications. Eur J Clin Pharmacol 1991;40(Suppl 1):S Product information for Tricor. AbbVie. North Chicago, IL February Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of fenofibrate combined with atorvastatin in the treatment of combined hyperlipidemia. J Am Coll Cardiol 2005;45: Vega GL, Ma PT, Cater NB, et al. Effects of adding fenofibrate (200 mg/day) to simvastatin (10 mg/day) in patients with combined hyperlipidemia and metabolic syndrome. Am J Cardiol 2003;91: Athyros VG, Papageorgiou AA, Athyrou VV, et al. Atorvastatin and micronized fenofibrate alone and in combination in type 2 diabetes with combined hyperlipidemia. Diabetes Care 2002;25: Murdock DK, Murdock AK, Murdock RW, et al. Long-term safety and efficacy of combination gemfibrozil and HMG-CoA reductase inhibitors for the treatment of mixed lipid disorders. Am Heart J 1999;138: Product information for Lopid. Pfizer. New York, NY May Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High- Density Lipoprotein Cholesterol Intervention Trial Study Group. New Engl J Med 1999;341: PharmacistsLetter.com ~ PrescribersLetter.com ~ PharmacyTechniciansLetter.com ~ NursesLetter.com

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10 (Clinical Resource #340933: Page 10 of 10) 51. Brown WV. Expert commentary: the safety of fibrates in lipid-lowering therapy. Am J Cardiol 2007;99:19C-21C. 52. Product information for Praluent. Sanofi-Aventis U.S. Bridgewater, NJ January Product monograph for Repatha. Amgen Canada. Mississauga, ON L5N 0A4. June Product information for Repatha. Amgen. Thousand Oaks, CA December Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372: Navarese EP, Kolodziejczak M, Schulze V, et al. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia: a systematic review and meta-analysis. Ann Intern Med 2015;163: U.S. Government Publishing Office. Withdrawal of approval of indications related to coadministration with statins in applications for niacin extendedrelease tablets and fenofibric acid delayed-release capsules. April 18, Federal Register;81(74): /pdf/ pdf. (Accessed March 29, 2018). 58. Koren MJ, Lundqvist P, Bolognese M, et al. Anti- PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab. J Am Coll Cardiol 2014;63: Stroes E, Colquhoun D, Sullivan D, et al. Anti- PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol 2014;63: Koren MJ, Scott R, Kim JB, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo controlled, phase 2 study. Lancet 2012;380: Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376: Insull W Jr. Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: a scientific review. South Med J 2006;99: Blom DJ, Hala T, Bolognese M, et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. New Engl J Med 2014;370: Brunetti L, DeSantis EH. Patient tolerance and acceptance of colesevelam hydrochloride: focus on type-2 diabetes mellitus. P T 2015;40: Merck. Merck statement on FDA advisory committee meeting on IMPROVE-IT study with Vytorin. December 14, (Accessed March 26, 2018). 66. Product information for Trilipix. AbbVie. North Chicago, IL October Product monograph for Praluent. Sanofi-Aventis Canada. Laval, QC H7V 0A3. May Cite this document as follows: Clinical Resource, Non- Lipid-Lowering Agents. Pharmacist s Letter/Prescriber s Letter. September Evidence and Recommendations You Can Trust 3120 West March Lane, Stockton, CA ~ TEL (209) ~ FAX (209) Copyright 2018 by Therapeutic Research Center Subscribers to the Letter can get clinical resources, like this one, on any topic covered in any issue by going to PharmacistsLetter.com, PrescribersLetter.com, PharmacyTechniciansLetter.com, or NursesLetter.com

11 PL Conversation Starter: Dyslipidemia PATIENT: DOB: Use this sheet as a guide to start conversations with your dyslipidemia patients during comprehensive medication reviews (CMRs), medication synchronization appointments, or during any patient interaction. Tackle one or two topics at a time, but don t overwhelm your patients or yourself by doing too much too fast. Start with these ideas and build on the topics below. Note that adherence to statins is a Star Ratings quality measure. 1. Assess adherence to lipid lowering medications. Emphasize importance. (Date discussed: ) Review prescription refill history to help assess adherence. Have patients explain how they take their medications and make sure your records match. Assess adherence by asking open ended questions, such as: It can be hard to take all your meds regularly. How many doses did you miss in the past week? What challenges keep you from consistently taking your medicines (e.g., cost, forgetfulness)? 2. Ensure patient is on appropriate statin therapy. (Date discussed: ) Discuss patient s cardiovascular risk. Visit use patient specifics and the online calculator to estimate patient s 10-year risk of heart disease or stroke. See our PL Chart, 2013 ACC/AHA Cholesterol Guidelines, to assess appropriateness of statin therapy, including dose. If therapy isn t appropriate, contact provider with rationale and recommend a change. Recommend moderate- to high-intensity statins for all diabetics age 40 to 75 years. Consider high-intensity statins for patients with cardiovascular disease or additional risk factors. Recommend starting with target statin doses, as titrating up doesn t improve tolerability. 3. Discuss the benefits and rare side effects associated with statin therapy. (Date discussed: ) Often there are no symptoms due to high cholesterol. Remind patients of statin benefits to encourage adherence: reduced peripheral artery disease (PAD), heart attacks (MIs), and strokes. Educate and reassure patient about less common side effects. Encourage patients to contact their provider if they notice: liver problems (e.g., dark urine, yellowing of eyes or skin, abdominal pain), memory problems (e.g., confusion, forgetfulness, clouded thinking), or diabetes (e.g., excessive hunger or thirst, unexplained weight loss). 4. Discuss muscle pain associated with statins. (Date discussed: ) Ensure appropriate statin-dose and screen for drug interactions to reduce the risk of muscle pain. See our PL Chart, Clinically Significant Drug Interactions, for meds to watch for. See our PL Chart, Muscle Symptoms: Managing Intolerance, for information on symptoms and tips to treat and reduce the risk of occurrence. Ask patients about potential causes: grapefruit intake, exercise, symptoms of hypothyroidism, etc. If muscle pain is intolerable, recommend (to prescriber) holding the statin for two to four weeks. Work with the prescriber to reduce recurrence: re-initiate at a lower dose, switch statins, or extend the dosing interval to every other day or even twice a week. Discourage coenzyme Q10 use, as data doesn t support a benefit for statin-associated muscle pain. If patients insist, recommend 100 to 200 mg daily. 5. Discuss healthy lifestyle choices (e.g., diet, physical activity, etc). (Date discussed: ) Encourage aerobic activity (e.g., brisk walking) >40 minutes, three or four times per week. Encourage at least five servings of fiber per day (e.g., fresh fruits and vegetables, cooked dry beans). Recommend psyllium 5.1 g twice daily for patients that don t like fruits and vegetables. Recommend limited intake of sugary foods and drinks. Recommend good fats, mono and polyunsaturated fats, (e.g., salmon, walnuts, sunflower seeds, avocado) and discourage bad fats, saturated and trans fats, (fatty meats, baked goods, fried foods). Encourage weight loss if appropriate, and a healthy body mass index (BMI) of 18.5 to Prepared for use by Pharmacist s Letter subscribers. Copyright 2016 by Therapeutic Research Center. [April 2016]