An Update on Pharmacotherapy of Dyslipidemia for Adults

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Sheikh Salahuddin Ahmed


Dyslipidemia is an important cause of atherosclerotic cardiovascular disease (ASCVD) worldwide that leads to increased risk of morbidity and mortality; treating dyslipidemia to goal reduces the risks. This article reviews the pharmacological therapy of dyslipidemia which is often required in addition to life style intervention to achieve target lipid levels. Currently, there are seven types of approved lipid modifying drugs which are effective in treating dyslipidemia when used singly or in combination. Statins are considered as first line drug and have been used extensively in the primary and secondary prevention of ASCVD. Ezetimibe is used as a first line add-on drug for patients already on a statin who have not reached their low density lipoprotein (LDL-C) goals; however, ezetimibe can be used as initial drug in statin intolerant patients. Bile acid sequestrants are a useful alternative to statins or ezetimibe in pregnant women or patients with liver disease. They also lower blood glucose and are useful in diabetes mellitus (DM). The PCSK9 inhibitors are powerful lipid modifying drugs, are expensive, need injection for delivery, and are used when statin in maximum doses with other drugs cannot lower the LDL-C level to targets in patients with very high CV risk. Fibrates have recently shown to slow the progression of microvascular diseases and are found beneficial for DM with hypertriglyceridemia and microvascular complications. Currently, niacin use is markedly decreased due to development of more effective alternative drugs for managing dyslipidemia and because of the adverse effects related to niacin use. Recent trials reveal that, ω-3 fatty acids, when added in pharmacological doses to statin therapy (after controlling LDL-C), are effective in reducing CV events in patients having moderate hypertriglyceridemia with high or very high CV risks.

Cholesterol lowering drugs, ezetimibe, fibrates, LDL-C lowering drugs, PCSK9 inhibitors, statins, triglyceride lowering drugs, treatment (drugs).

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Ahmed, S. S. (2020). An Update on Pharmacotherapy of Dyslipidemia for Adults. Journal of Advances in Medicine and Medical Research, 32(8), 86-109.
Review Article


Fodor G. Primary Prevention of CVD: Treating Dyslipidemia. Am Fam Physician. 2011;83(10):1207-08.

Brunzell JD, Davidson M, Furberg CD, Goldberg RB, Howard BV, Stein JH, et al. Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J Am Coll Cardiol. 2008;51(15):1512-24.

Emerging Risk Factors Collaboration, Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, White IR, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302: 412–23.

Nordestgaard BG, Chapman MJ, Ray K, Borén J, Andreotti F, Watts GF, Ginsberg H, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31:2844–53.

Ahmed SS. Treating dyslipidemia in adults: An Update. JAMMR. 2020;32(5): 114-35.

Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA. 1986;256: 2835-38.

Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low‐density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017; 38:2459–72.

Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH, et al. Evaluation and treatment of hypertri-glyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012;97:2969-89.

Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk: European Heart Journal. 2020;41(1):111-188.

Ahmed SS. Dietary and Blood Lipids in Cardiovascular Disease. JAMMR. 2020; 32(2):11-21.

Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. Cholesterol Clinical Practice Guidelines 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol. A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082–e1143.

Originally published10 Nov 2018


Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. Odyssey outcomes Committees and Investigators. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097-2107.

Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, et al; Open- Label Study of Long-Term Evaluation against LDL Cholesterol (OSLER) Investigators. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1500-09.

Ministry of Health Malaysia Clinical Practice Guidelines. Management of Dyslipidemia; 2017.


Accessed 21 February 2019.

Ministry of health Singapore. Lipids. MOH Clinical Practice Guidelines 2/2016. Available:

(Accessed 01 December 2020)

Rhee EJ, Kim HC, Kim JH, Lee EY, Kim BJ, Kim EM, et al. Guidelines for the management of dyslipidemia in Korea. Korean J Intern Med. 2019;34(4):723–71.

Feingold KR. Triglyceride Lowering Drugs. Endotext. Updated; 2020.


(Accessed 15 April 2020)

Maki KC, Orloff DG, Nicholls SJ, Dunbar RL, Roth EM, Curcio D, et al. A highly bioavailable omega-3 free fatty acid formulation improves the cardiovascular risk profile in high-risk, statin-treated patients with residual hypertriglyceridemia (the ESPRIT trial). Clin Ther. 2013;35(9): 1400-11.e1-3.

Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 1–full report. J Clin Lipidol. 2015;9:129–69.

Griffin JD, Lichtenstein AH. Dietary cholesterol and plasma lipoprotein profiles: randomized-controlled trials. Curr Nutr Rep. 2013;2:274-82.

Maki KC, Guyton JR, Orringer CE, Hamilton-Craig I, Alexander DD, Davidson MH. Triglyceride-lowering therapies reduce cardiovascular disease event risk in subjects with hypertriglyceridemia. J Clin Lipidol. 2016;10:905-14.

Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019; 380:11-22.

Orringer CE, Jacobson TA, Maki KC. National lipid association scientific statement on the use of icosapent ethyl in statin-treated patients with elevated TGs and high or very-high ASCVD risk. J Clin Lipidol. 2019;13:860-72.

Kumar S, Rai H, Kapoor A, Tewari S, Sinha N. Pharmacological measures to increase HDL-C among high risk isolated low HDL cases: a randomized study amongst north Indians. Indian J Med Res. 2013;138(6):873‐81.

Aim High Investigators, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-67.

Andrews J, Janssan A, Nguyen T, Pisaniello AD, Scherer DJ, Kastelein JJ, et al. Effect of serial infusions of reconstituted high-density lipoprotein (CER-001) on coronary atherosclerosis: rationale and design of the CARAT study. Cardiovasc Diagn Ther. 2017;7:45-51.

Kim NH, Han KH, Choi J, Lee J, Kim SG. Use of fenofibrate on cardiovascular outcomes in statin users with metabolic syndrome: propensity matched cohort study. BMJ. 2019;366:l5125.


Bhowmik B, Siddiquee T, Mujumder A, Afsana F, Ahmed T, Mdala IA, et al. Serum lipid profile and its association with diabetes and prediabetes in a rural Bangladeshi population. Int J Environ Res Public Health. 2018;15(9):1944.

Available: 10.3390/ijerph15091944

Chakraborty M, Gouroju S, Singh P, Thatkar PV, Bagchi D. Tracking lipid profile and atherogenic indices in the prediabetics of Andaman Nicobar Islands: A retrospective hospital-based study. J Family Med Prim Care. 2019;8:1117–22.

Chehade JM, Gladysz M, Mooradian AD. Dyslipidemia in type 2 diabetes: prevalence, pathophysiology, and manage-ment. Drugs. 2013;73(4):327–39.

Márk L, Dani G. Diabetic Dyslipidaemia and the Atherosclerosis. Orv Hetil. 2016; 157(19):746-52.

Accord Study Group, Ginsberg HN, Elam MB, Lovato LC, Crouse JR 3rd, Leiter LA, et al. Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus. New Engl J Med. 2010;362(17):1563-74.

Bos S, Yayha R, van Lennep JE. Latest developments in the treatment of lipoprotein (a). Curr Opin Lipidol. 2014;25: 452-60.

Feingold KR. Cholesterol Lowering Drugs. Updated: March 29, 2020.


Accessed on 15 Apr 2020.

Bittner VA, Szarek M, Aylward PE, Bhatt DL, Diaz R, Edelberg JM, et al and for the Odyssey ouTCOMES Committees and Investigators. Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome. J Am Coll Cardiol. 2020;75(2):133-44.

Chasman DI, Giulianini F, MacFadyen J, Barratt BJ, Nyberg F, Ridker PM. Genetic determinants of statin-induced low-density lipoprotein cholesterol reduction: The Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial. Circ Cardiovasc Genet. 2012;5:257-64.

Reiner Z. Managing the residual cardiovascular disease risk associated with HDL-cholesterol and triglycerides in statin-treated patients: a clinical update. Nutr Metab Cardiovasc Dis. 2013;23:799-807.

Stein EA, Lane M, Laskarzewski P. Comparison of statins in hypertri-glyceridemia. Am J Cardiol. 1998;81:66B-69B.


Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003; 92(2):152-60.

Adams SP, Tsang M, Wright JM. Lipid-lowering efficacy of atorvastatin. Cochrane Database Syst Rev. 2015;3:CD008226.doi: 10.1002/14651858.CD008226.pub3.

Huff MW, Burnett JR. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and hepatic apolipoprotein B secretion. Curr Opin Lipidol. 1997;8:138-45.

Jones P, Kafonek S, Laurora I, Hunninghake D. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hyperchole-sterolemia (the CURVES study). Am J Cardiol. 1998;81(5):582-87.

Plakogiannis R, Cohen H. Optimal low-density lipoprotein cholesterol lowering--morning versus evening statin administra-tion. Ann Pharmacother. 2007;41:106–110.

Awad K, Serban MC, Penson P, Mikhailidis DP, Toth PP, Jones SR, et al. Lipid, blood pressure meta-analysis collaboration G. effects of morning vs evening statin administration on lipid profile: A systematic review and meta-analysis. J Clin Lipidol. 2017;11:972-985 e979.

DOI: 10.1016/j.jacl.2017.06.001.

Stone NJ, Robinson JG, Lichtenstein AH, BaireyMerz CN, Blum CB, Eckel RH, 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. Circulation. 2014;129(25 Suppl 2):S1-45.

Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267-78.

Parker BA, Capizzi JA, Grimaldi AS, Clarkson PM, Cole SM, Keadle J, et al. Effect of Statins on Skeletal Muscle Function. Circulation. 2013;127:96–103.

Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, et al; European Atherosclerosis Society Consensus Panel. Statin-associated muscle symptoms: impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J. 2015;36:1012-22.

Ganga HV, Slim HB, Thompson PD. A systematic review of statin-induced muscle problems in clinical trials. Am Heart J. 2014;168:6–15.

Hamann PDH, Cooper RG, McHugh NJ, Chinoy H. Statin-induced necrotizing myositis: a discrete autoimmune entity within the statin-induced myopathy spectrum. Autoimmun Rev. 2013;12:1177–81.

Mammen AL. Statin-Associated Autoimmune Myopathy. N Engl J Med. 2016;374:664-69.

McKenney JM, Davidson MH, Jacobson TA, Guyton JR. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardiol. 2006;97(8A): 89C-94C.

DOI: 10.1016/j.amjcard.2006.02.030

Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: A Therapeutic Dilemma. Mayo Clin Proc. 2010;85:349–56.

Chalasani N, Aljadhey H, Kesterson J, Murray MD, Hall SD. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroentero-logy. 2004;126:1287-92.

Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol. 2006; 97:52C-60C.

DOI: 10.1016/j.amjcard.2005.12.010

Mancini GB, Baker S, Bergeron J, Fitchett D, Frohlich J, Genest J, et al. Diagnosis, prevention and management of statin adverse effects and intolerance: proceedings of a Canadian Working Group Consensus Conference. Can J Cardiol. 2011;27(5):635-62.

Preiss D, Seshasai SRK, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy: A Meta-analysis. JAMA. 2011; 305:2556–64.

Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, et al. Statins and risk of incident diabetes:a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375(9716):735-42.

Agarwal R. Effects of statins on renal function. Am J Cardiol. 2006;97:748-55.

Causevic-Ramosevac A, Semiz S. Drug interactions with statins. Acta Pharm. 2013;63:277-93.

Lee JW, Morris JK, Wald NJ. Grapefruit Juice and Statins. Am J Med. 2016;129:26-29.

Vaughan CJ, Gotto AM, Jr. Update on statins: 2003. Circulation. 2004;110(7): 886-92.

Bays H, Rhyne J, Abby S, Lai YL, Jones M. Lipid-lowering effects of colesevelam HCl in combination with ezetimibe. Curr Med Res Opin. 2006;22:2191-2200.

Foster T, Budoff MJ, Saab S, Ahmadi N, Gordon C, Guerci AD. Atorvastatin and antioxidants for the treatment of nonalcoholic fatty liver disease: the St Francis Heart Study randomized clinical trial. Am J Gastroenterol. 2011;106:71–7.

Samaras K, Makkar SR, Crawford JD, Kochan NA, Slavin MJ, Wen W, et al. Effects of statins on memory, cognition, and brain volume in the elderly. J Am Coll Cardiol. 2019;74(21):2554‐68.

Cholesterol Treatment Trialists’ (CTT) Collaborators, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380:581–90.

Cholesterol Treatment Trialists’ (CTT) Collaboration; Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. 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: 1670–81.

Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. New Engl J Med. 2015;372:2387-97.

Morrone D, Weintraub WS, Toth PP, Hanson ME, Lowe RS, Lin J, et al. Lipid-altering efficacy of ezetimibe plus statin and statin monotherapy and identification of factors associated with treatment response: A pooled analysis of over 21,000 subjects from 27 clinical trials. Atherosclerosis. 2012;223:251-61.

Pandor A, Ara RM, Tumur I, Wilkinson AJ, Paisley S, Duenas A, et al. Ezetimibe monotherapy for cholesterol lowering in 2,722 people: systematic review and meta-analysis of randomized controlled trials. J Intern Med. 2009;265:568-80.

Ballantyne CM, Weiss R, Moccetti T, Vogt A, Eber B, Sosef F, et al, Investigators ES. Efficacy and safety of rosuvastatin 40 mg alone or in combination with ezetimibe in patients at high risk of cardiovascular disease (results from the Explorer study). Am J Cardiol. 2007;99:673-80.

Jones MR, Nwose OM. Role of colesevelam in combination lipid-lowering therapy. Am J Cardiovasc Drugs. 2013; 13:315-23.

Sahebkar A, Simental-Mendia LE, Pirro M, Banach M, Watts GF, Sirtori C, et al. Impact of ezetimibe on plasma lipoprotein(a) concentrations as monotherapy or in combination with statins: a systematic review and meta-analysis of randomized controlled trials. Sci Rep. 2018;8(1):17887.

DOI: 10.1038/s41598-018-36204-7

Turley SD, Dietschy JM. Sterol absorption by the small intestine. Curr Opin Lipidol. 2003;14:233-40.

Bruckert E, Giral P, Tellier P. Perspectives in cholesterol-lowering therapy: the role of ezetimibe, a new selective inhibitor of intestinal cholesterol absorption. Circulation. 2003;107:3124-28.

Telford DE, Sutherland BG, Edwards JY, Andrews JD, Barrett PH, Huff MW. The molecular mechanisms underlying the reduction of LDL apoB-100 by ezetimibe plus simvastatin. J Lipid Res. 2007;48:699-708.

Phan BA, Dayspring TD, Toth PP. Ezetimibe therapy: mechanism of action and clinical update. Vasc Health Risk Manag. 2012;8:415-27.

Wu H, Shang H, Wu J. Effect of ezetimibe on glycemic control: a systematic review and meta-analysis of randomized controlled trials. Endocrine. 2018;60:229-39.

Ooi CP, Loke SC. Colesevelam for type 2 diabetes mellitus: an abridged Cochrane review. Diabet Med. 2014;31:2-14.

Insull W Jr. Clinical utility of bile acid sequestrants in the treatment of dyslipidemia: A scientific review. South Med J. 2006;99:257-73.

Aldridge MA, Ito MK. Colesevelam hydrochloride: A novel bile acid-binding resin. Ann Pharmacother. 2001;35:898-907.

Huijgen R, Abbink EJ, Bruckert E, Stalenhoef AF, Imholz BP, Durrington PN, et al. Triple study group. Colesevelam added to combination therapy with a statin and ezetimibe in patients with familial hypercholesterolemia: A 12-week, multicenter, randomized, double-blind, controlled trial. Clin Ther. 2010;32:615-25.

Zema MJ. Colesevelam HCl and ezetimibe combination therapy provides effective lipid-lowering in difficult-to-treat patients with hypercholesterolemia. Am J Ther. 2005;12:306-10.

Einarsson K, Ericsson S, Ewerth S, Reihner E, Rudling M, Stahlberg D, et al. Bile acid sequestrants: mechanisms of action on bile acid and cholesterol metabolism. Eur J Clin Pharmacol. 1991; (40 Suppl1):S53-58.

Mazidi M, Rezaie P, Karimi E, Kengne AP. The effects of bile acid sequestrants on lipid profile and blood glucose concentrations: A systematic review and meta-analysis of randomized controlled trials. Int J Cardiol. 2017;227:850-57.

Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly DD, DePalma SM, et al. ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2016;68: 92–125.

Ito MK, McGowan MP, Moriarty PM, National Lipid Association Expert Panel on Familial Hypercholesterolemia. Manage-ment of familial hypercholesterole-mias in adult patients: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011;5:S38-45.

Navarese EP, Kolodziejczak M, Schulze V, Gurbel PA, Tantry U, Lin Y, 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; 163:40–51.

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al; Fourier Steering Committee and Investigators. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713-22.

Lambert G, Sjouke B, Choque B, Kastelein JJ, Hovingh GK. The PCSK9 decade. J Lipid Res 2012;53:2515-24.

Norata GD, Tibolla G, Catapano AL. Targeting PCSK9 for hypercholesterole-mia. Annu Rev PharmacolToxicol. 2014; 54:273–93.

Cicero AF, Tartagni E, Ertek S. Safety and tolerability of injectable lipid-lowering drugs: a review of available clinical data. Expert Opin Drug Saf. 2014;13:1023- 30.

Abourbih S, Filion KB, Joseph L, Schiffrin EL, Rinfret S, Poirier P, et al. Effect of fibrates on lipid profiles and cardiovascular outcomes: a systematic review. Am J Med. 2009;122:962.e1-8.

DOI: 10.1016/j.amjmed.2009.03.030

Choi HD, Shin WG. Safety and efficacy of statin treatment alone and in combination with fibrates in patients with dyslipidemia: A meta-analysis. Curr Med Res Opin. 2014;30(1):1-10.

Staels B, et al. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation. 1998;98(19): 2088-93.

Shah A, Rader DJ, Millar JS. The effect of PPAR-alpha agonism on apolipoprotein metabolism in humans. Atherosclerosis. 2010;210(1):35-40.

Chapman MJ, Redfern JS, McGovern ME, Giral P. Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk. Pharmacol Ther. 2010; 126:314-45.

Rosenson RS. Fenofibrate: treatment of hyperlipidemia and beyond. Expert Rev Cardiovasc Ther. 2008;6(10):1319-30.

Zimetbaum P, Frishman WH, Kahn S. Effects of gemfibrozil and other fibric acid derivatives on blood lipids and lipoproteins. J Clin Pharmacol. 1991;31(1):25-37.

Miller M, Bachorik PS, McCrindle BW, Kwiterovich Jr PO. Effect of gemfibrozil in men with primary isolated low high-density lipoprotein cholesterol: A randomized, double-blind, placebo-controlled, crossover study. Am J Med. 1993;94(1):7-12.

Berthold HK, Gouni-Berthold. Hyperlipo-proteinemia(a): clinical significance and treatment options. Atheroscler Suppl. 2013;14(1):1-5.

Keech AC, Mitchell P, Summanen PA, O'Day J, Davis TME, Moffitt MS, et al. Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): A randomised controlled trial. Lancet. 2007;370(9600):1687-97.

ACCORD Study Group; ACCORD Eye Study Group, Chew EY, Ambrosius WT, Davis MD, Danis RP, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med. 2010;363(3):233-44.

Kouroumichakis I, Papanas N, Zarogoulidis P, Liakopoulos V, Maltezos E, et al. Fibrates: therapeutic potential for diabetic nephropathy? Eur J Intern Med. 2012;23(4):309-16.

Davis TME, Ting R, Best JD, Donoghoe MW, Drury PL, Sullivan DR, et al. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Diabetologia. 2011;54(2):280-90.

Ansquer JC, Dalton RN, Caussé E, Crimet D, Malicot KL, Foucher C. Effect of fenofibrate on kidney function: a 6-week randomized crossover trial in healthy people. Am J Kidney Dis. 2008;51(6):904-13.

Waldman B, Ansquer JC, Sullivan DR, Jenkins AJ, McGill N, Buizen L, et al. Effect of fenofibrate on uric acid and gout in type 2 diabetes: a post-hoc analysis of the randomised, controlled FIELD study. Lancet Diabetes Endocrinol. 2018;6(4): 310-318.

Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety considerations with fibrate therapy. Am J Cardiol. 2007; 99(6A):3C-18C.

DOI: 10.1016/j.amjcard.2006.11.016

Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate + statin versus gemfibrozil + any statin. Am J Cardiol. 2005;95(1):120-22.

Preiss D, Tikkanen MJ, Welsh P, Ford I, Lovato LC, Elam MB, et al. Lipid modifying therapies and risk of pancreatitis: a meta-analysis. JAMA. 2012;308:804-11.

Jun M, Foote C, Lv J, Neal B, Patel A, Nicholls SJ, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010; 375:1875-84.

Wang D, Liu B, Tao W, Hao Z, Liu M. Fibrates for secondary prevention of cardiovascular disease and stroke. Cochrane Database Syst Rev. 2015(10): CD009580.

DOI: 10.1002/14651858.CD009580.pub2

Bruckert E, Labreuche J, Deplanque D, Touboul PJ, Amarenco P. Fibrates effect on cardiovascular risk is greater in patients with high triglyceride levels or atherogenic dyslipidemia profile: A systematic review and meta-analysis. J Cardiovasc Pharmacol. 2011;57(2):267-72.

Song WL, FitzGerald GA. Niacin, an old drug with a new twist. J Lipid Res. 2013; 54(10):2586-94.

Julius U. Niacin as antidyslipidemic drug. Can J Physiol Pharmacol. 2015;93(12): 1043-54.

Altschul R, Hoffer A, Stephen JD. Influence of nicotinic acid on serum cholesterol in man. Arch Biochem Biophys. 1955;54(2): 558-59.

Birjmohun RS, Hutten BA, Kastelein JJ, Stroes ES. Efficacy and safety of high-density lipoprotein cholesterol-increasing compounds: A meta-analysis of randomized controlled trials. J Am Coll Cardiol. 2005;45(2):185-97.

Davidson MH, Rooney M, Pollock E, Drucker J, Choy Y. Effect of colesevelam and niacin on low-density lipoprotein cholesterol and glycemic control in subjects with dyslipidemia and impaired fasting glucose. J Clin Lipidol. 2013;7(5): 423-32.

HPS2-Thrive Collaborative Group; Landray MJ, Haynes R, Haynes R, Hopewell JC, Parish S, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203-12.

Kamanna VS, Ganji SH, Kashyap ML. Recent advances in niacin and lipid metabolism. Curr Opin Lipidol. 2013;24(3): 239-45.

Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol. 2008;101: 20B-26B. DOI:10.1016/j.amjcard.2008.02.029

Croyal, M, Ouguerram K, Passard M, Ferchaud-Roucher V, Chétiveaux M, Billon-Crossouard S, et al. Effects of extended-release nicotinic acid on apolipoprotein (a) kinetics in hypertri-glyceridemic patients. Arterioscler thrombvasc Biol. 2015;35(9):2042-47.

Goldberg AC. A meta-analysis of randomized controlled studies on the effects of extended-release niacin in women. Am J Cardiol. 2004;94(1):121-24.

Miettinen TA, Taskinen MR, Pelkonen R, Nikkilä EA. Glucose tolerance and plasma insulin in man during acute and chronic administration of nicotinic acid. Acta Med Scand. 1969;186(4):247-53.

Elam MB, Hunninghake DB, Davis KB, Garg R, Johnson C, Egan D, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: The ADMIT study: A randomized trial. Arterial Disease Multiple Intervention Trial. JAMA. 2000; 284(10):1263-70.

Kashyap ML, Ganji S, Nakra NK, Kamanna VS. Niacin for treatment of nonalcoholic fatty liver disease (NAFLD): novel use for an old drug? J ClinLipidol. 2019;13:873-79.

Sacks FM, Lichtenstein AH, Wu JHY, Appel LJ, Creager MA, Kris-Etherton PM, et al; American Heart Association. Dietary fats and cardiovascular disease: A presidential advisory from the American Heart Association. Circulation. 2017; 136(3):e1-e23.

DOI: 10.1161/cir.0000000000000510

Wei MY, Jacobson TA. Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. Curr Atheroscler Rep. 2011;13:474-83.

Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk. 1997;4(5-6):385-91.

Roth EM, Bays HE, Forker AD, Maki KC, Carter R, Doyle RT, et al. Prescription omega-3 fatty acid as an adjunct to fenofibrate therapy in hypertriglyceridemic subjects. J Cardiovasc Pharmacol. 2009; 54(3):196-203.

Shearer GC, Pottala JV, Hansen SN, Brandenburg V, Harris WS. Effects of prescription niacin and omega-3 fatty acids on lipids and vascular function in metabolic syndrome: a randomized controlled trial. J Lipid Res. 2012;53(11):2429-35.

Kastelein JJ, Maki KC, Susekov A, Ezhov M, Nordestgaard BG, Machielse BN, et al. Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: The EpanoVafOr Lowering Very high triglyceridEs (EVOLVE) trial. J Clin Lipidol. 2014;8:94-106.

Eslick GD, Howe PR, Smith C, Priest R, Bensoussan A. Benefits of fish oil supplementation in hyperlipidemia: A systematic review and meta-analysis. Int J Cardiol. 2009;136(1):4-16.

Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: A systematic review. Atherosclerosis. 2006;189(1):19-30.

Manson JE, Cook NR, Lee I-M, Christen W, Bassuk SS, Mora S, et al. VITAL Research Group. Marine n−3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med. 2019;380:23-32.

Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, et al. Omega-3 treatment trialists’ collaboration. associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77 917 individuals. JAMA Cardiol. 2018;3:225-34.

Li ZH, Zhong WF, Liu S, Kraus VB, Zhang YZ, Gao X, et al. Associations of habitual fish oil supplementation with cardiovascular outcomes and all-cause mortality: evidence from a large population based cohort study. BMJ. 2020;368:m456. DOI: 10.1136/bmj.m456.

Shearer GC, Savinova OV, Harris WS. Fish oil -- how does it reduce plasma triglycerides? Biochim Biophys Acta. 2012; 1821(5):843-51.

Davidson MH. Mechanisms for the hypotriglyceridemic effect of marine omega-3 fatty acids. Am J Cardiol. 2006; 98(4A):27i-33i.

DOI: 10.1016/j.amjcard.2005.12.024

Wachira JK, Larson MK, Harris WS. n-3 Fatty acids affect haemostasis but do not increase the risk of bleeding: clinical observations and mechanistic insights. Br J Nutr. 2014;111(9):1652-62.

de Lemos JA, Blazing MA, Wiviott SD, Lewis EF, Fox KAA, White HD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004;292:1307-16.

Stefanutti C, Thompson GR. Lipoprotein apheresis in the management of familial hypercholesterolaemia: Historical perspective and recent advances. Curr Atheroscler Rep. 2015;17(1):465.

DOI: 10.1007/s11883-014-0465-6

Czupryniak L, Joshi SR, Gogtay JA, Lopez M. Effect of micronized fenofibrate on microvascular complications of type 2 diabetes: A systematic review. Expert Opin Pharmacother. 2016;17(11):1463- 73.

Wanner C, Krane V, Marz W, Olschewski M, Mann JF, Ruf G, et al. Atorvastatin in Patients with Type 2 Diabetes Mellitus Undergoing Hemodialysis. N Engl J Med. 2005;353(3):238-48.

Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, et al. Cholesterol lowering in intermediate- risk persons without cardiovascular disease. N Engl J Med. 2016;374:2021–31.

Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto Jr AM, Kastelein JJP, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359: 2195–207.