Dyslipidemia: Contemporary Therapy Options in Terms of Worldwide Guidelines
- 70 Downloads
Purpose of Review
Statins represent a golden standard for treating patients with dyslipidemia. At half of the treated patients, the targeted level of LDL cholesterol is not achieved. Numerous studies which promote new medications have been published in the past several years. Therefore, the objective of this paper is to consider the new possibilities of treating dyslipidemia in terms of various dyslipidemia guidelines.
Randomized clinical trials have shown that most positive effects are achieved by lowering the level of LDL cholesterol, and thus the guidelines define the target LDL value. Numerous guidelines in the field of dyslipidemia have been published, but there are some differences which will be analyzed in this review paper. Even if the target LDL cholesterol level is reached, there is still a residual lipid risk for the occurrence of cardiovascular diseases. Therefore, lipid factors, such as high level of triglycerides, low HDL cholesterol, LP(a), etc., play a very important role. Nowadays, there are numerous potent medications which are used in statin and non-statin therapies. PCSK9 inhibitors, which are in the special focus of this paper, have been tested in the past few years. The paper offers an overview of traditionally used medications, as well as new experimental medications. Moreover, the paper emphasizes the importance of non-adherence to antilipemic medications, which is an important issue which reduces the favorable effects of the treatment.
Nowadays, there are drugs which, combined with statins, may reduce HDL-C level to very low values. The studies have shown inconsistent results in terms of solving the issue of residual lipid risk. Research in this field may significantly reduce lipid risk for cardiovascular events.
KeywordsDyslipidemia Treating dyslipidemia Guidelines Target level Statins Residual lipid risk
We hereby thank Jasmina Nedeljkovic for providing language and proofreading assistance during the creation of this paper.
Compliance with Ethical Standards
Conflict of Interest
Djordjevic B. Dragan, Dordevic D. Aleksandar, and Lovic B. Dragan declare no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Beaumont JL, Carlson LA, Cooper GR, Fejfar Z, Fredrickson DS, Strasser T. Classification of hyperlipidaemias and hyperlipoproteinaemias. Bull World Health Organ. 1970;43:891–5.Google Scholar
- 6.Patnode CD, Evans CV, Senger CA, Redmond N, Lin JS. Behavioral counseling to promote a healthful diet and physical activity for cardiovascular disease prevention in adults without known cardiovascular disease risk factors: updated evidence report and systematic review for the US preventive services task force. JAMA. 2017;318:175–93. https://doi.org/10.1001/jama.2017.3303.
- 7.• Marques LR, Diniz TA, Antunes BM, Rossi FE, Caperuto EC, Lira FS, et al. Reverse cholesterol transport: molecular mechanisms and the non-medical approach to enhance hdl cholesterol. Front Physiol. 2018;9:526. https://doi.org/10.3389/fphys.2018.00526. The paper discusses non-medical approaches and molecular mechanisms and effects of physical on lipid status change, especially in terms of HDL cholesterol. CrossRefGoogle Scholar
- 8.Loftus HL, Astell KJ, Mathai ML, Su XQ. Coleus for skohlii extract supplementation in conjunction with a hypocaloric diet reduces the risk factors of metabolic syndrome in overweight and obese subjects: a randomized controlled trial. Nutrients. 2015;7:9508–22. https://doi.org/10.3390/nu7115483.CrossRefGoogle Scholar
- 15.•• Zodda D, Giammona R, Schifilliti S. Treatment strategy for dyslipidemia in cardiovascular disease prevention: focus on old and new drugs. Pharmacy. 2018;6:10. https://doi.org/10.3390/pharmacy6010010. A detailed overview of old and new drugs for treating dyslipidemia is offered, with special emphasis on clinical trials with new drugs. CrossRefGoogle Scholar
- 18.Gille A, Bodor ET, Ahmed K, Offermanns S. Nicotinic acid: pharmacological effects and mechanisms of action. Ann Rev Pharmacol Toxicol. 2008;48:79–106. https://doi.org/10.1146/annurev.pharmtox.48.113006.094746.CrossRefGoogle Scholar
- 19.Kwak SM, Myung SK, Lee YJ, Seo HG, Korean Meta-Analysis Study Group. 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;172:686–94. https://doi.org/10.1001/archinternmed.2012.262.CrossRefGoogle Scholar
- 20.•• Polychronopoulos G, Tziomalos K. Novel treatment options for the management of heterozygous familial hypercholesterolemia. Expert Rev Clin Pharmacol. 2017;10:1375–81. https://doi.org/10.1080/17512433.2017.1378096. Contemporary possibilities of treating heterozygous familial hypercholesterolemia have been presented, as well as experimental research and future prospects. CrossRefGoogle Scholar
- 21.Cuchel M, Meagher EA, du Toit Theron H, Blom DJ, Marais AD, Hegele RA, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet. 2013;381:40–6. https://doi.org/10.1016/S0140-6736(12)61731-0.CrossRefGoogle Scholar
- 24.• Wicinski M, Zak J, Malinowski B, Popek G, Grzesk G. PCSK9 signaling pathways and their potential importance in clinical practice. EPMA J. 2017;8:391–402. https://doi.org/10.1007/s13167-017-0106-6. This reference provides a thorough summary of signal paths and clinical significance of PCSK9 inhibitors, as well as other possible alternative drugs. CrossRefGoogle Scholar
- 27.Dong B, WuM LH, Kraemer FB, Adeli K, Seidah NG, et al. Strong induction of PCSK9 gene expression through HNF1alpha and SREBP2: mechanism for the resistance to LDL-cholesterol lowering effect of statins in dyslipidemic hamsters. J Lipid Res. 2009;51:1486–95. https://doi.org/10.1194/jlr.M003566.CrossRefGoogle Scholar
- 30.Ruscica M, Ricci C, Macchi C, Magni P, Cristofani R, Liu J, et al. Suppressor of cytokine signaling 3 (SOCS3) induces proprotein convertase subtilisin kexin type 9 (PCSK9) expression in hepatic HepG2 cell line. J Biol Chem. 2016;291:3508–19. https://doi.org/10.1074/jbc.M115.664706.CrossRefGoogle Scholar
- 36.Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz 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. J Am Coll Cardiol. 2014;63:2889–934. https://doi.org/10.1161/01.cir.0000437738.63853.7a.CrossRefGoogle Scholar
- 38.Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, Garber AJ, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for the management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017;23:1–87. https://doi.org/10.4158/EP171764.APPGL.CrossRefGoogle Scholar
- 39.Anderson TJ, Gregoire J, Pearson GJ, Barry AR, Couture P, Dawes M, et al. 2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2016;32:1263–82. https://doi.org/10.1016/j.cjca.2016.07.510.CrossRefGoogle Scholar
- 43.• Mortensen MB, Nordestgaard BG. Comparison of five major guidelines for statin use in primary prevention in a contemporary general population. Ann Intern Med. 2018;168:85–92. https://doi.org/10.7326/M17-0681. The reference presents the similarities and differences between various leading guidelines on dyslipidemia in clear and concise way. CrossRefGoogle Scholar
- 44.Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB Sr, Gibbons R, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force On Practice Guidelines. J Am Coll Cardiol. 2014;63:2935–59. https://doi.org/10.1016/j.jacc.2013.11.005.CrossRefGoogle Scholar
- 45.Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: The SixthJoint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J. 2016;37:2315–81. https://doi.org/10.1093/eurheartj/ehw106.CrossRefGoogle Scholar
- 48.Mihaylova B, Emberson J, Blackwell L, for the Cholesterol Treatment Trialists. 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. https://doi.org/10.1016/S0140-6736(12)60367-5.CrossRefGoogle Scholar
- 49.• Soran H, Dent R, Durrington P. Evidence-based goals in LDL-C reduction. Clin Res Cardiol. 2017;106:237–48. https://doi.org/10.1007/s00392-016-1069-7. This reference discusses the possibilities, justification and safety of lowering LDL-C level, all with the aim of reducing cardiovascular risk. CrossRefGoogle Scholar
- 50.Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012;60:2631–9. https://doi.org/10.1016/j.jacc.2012.09.017.CrossRefGoogle Scholar
- 51.Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly DD Jr, DePalma SM, et al. 2016 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. https://doi.org/10.1016/j.jacc.2016.03.519.CrossRefGoogle Scholar
- 52.Reiner Z, De Backer G, Fras Z, Kotseva K, Tokgoyoglu L, Wood D, et al. Lipid lowering drugs therapy in patients with coronary heart disease from 24 European countries – findings from the EUROASPIRE IV study. Atherosclerosis. 2016;246:243–50. https://doi.org/10.1016/j.atherosclerosis.2016.01.018.CrossRefGoogle Scholar
- 54.Danese MD, Gleeson M, Kutikova L, Griffiths RI, Khunti K, Seshasai SRK, et al. Management of lipid-lowering therapy in patients with cardiovascular events in the UK: a retrospective cohort study. BMJ Open. 2017;7:e013851. https://doi.org/10.1136/bmjopen-2016-013851.
- 56.Sabatine MS, Giugliano RP, Wiviott SD. Open-label study of long-term evaluation against LDL cholesterol (OSLER) investigators et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1500–9. https://doi.org/10.1056/NEJMoa1500858.CrossRefGoogle Scholar
- 61.Hsia J, MacFadyen JG, Monyak J, Ridker PM. Cardiovascular event reduction and adverse events among subjects attaining low-density lipoprotein cholesterol \50 mg/dl with rosuvastatin the JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin). J Am Coll Cardiol. 2011;57:1666–75. https://doi.org/10.1016/j.jacc.2010.09.082.CrossRefGoogle Scholar
- 63.Richardson K, Schoen M, French B, Umscheid CA, Mitchell MD, Arnold SE, et al. Statins and cognitive function: a systematic review. Ann Intern Med. 2013;159:688–97. https://doi.org/10.7326/0003-4819-159-10-201311190-00007.CrossRefGoogle Scholar
- 67.Triglyceride Coronary Disease Genetics, Consortium and Emerging Risk Factors Collaboration, Sarwar N, Sandhu MS, Ricketts SL, Butterworth AS, Di Angelantonio E, et al. Triglyceride mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet. 2010;375:1634–9. https://doi.org/10.1016/S0140-6736(10)60545-4.CrossRefGoogle Scholar
- 69.Iso H, Imano H, Yamagishi K, Ohira T, Cui R, Noda H, et al. Fasting and non-fasting triglycerides and risk of ischemic cardiovascular disease in Japanese men and women; the Circulatory Risk in Communities Study (CIRCS). Atherosclerosis. 2014;237:361–8. https://doi.org/10.1016/j.atherosclerosis.2014.08.028.CrossRefGoogle Scholar
- 70.Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Bore’n J, Catapano AL, et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011;32:1345–61. https://doi.org/10.1093/eurheartj/ehr112.CrossRefGoogle Scholar
- 71.Ip CK, Jin DM, Gao JJ, Meng Z, Meng J, Tan Z, et al. Effects of add-on lipid-modifying therapy on top of background statin treatment on major cardiovascular events: a meta-analysis of randomized controlled trials. Int J Cardiol. 2015;191:138–48. https://doi.org/10.1016/j.ijcard.2015.04.228.CrossRefGoogle Scholar
- 76.Niesor EJ, Schwartz GG, Perez A, Stauffr A, Durrwell A, Bucklar-Suchankova G, et al. Statin-induced decrease in ATP-binding cassette transporter A1 expression via microRNA33 induction may counteract cholesterol efflux to high-density lipoprotein. Cardiovasc Drugs Ther. 2015;29:7–14. https://doi.org/10.1007/s10557-015-6570-0.CrossRefGoogle Scholar
- 79.Aubert RE, Yao J, Xia F, Garavaglia SB. Is there a relationship between early statin compliance and a reduction in healthcare utilization? Am J Anag Care. 2010;16:459–66.Google Scholar
- 80.Guglielmi V, Bellia A, Pecchioli S, Della-Morte D, Parretti D, Cricelli I, et al. Effectiveness of adherence to lipid lowering therapy on LDL cholesterol in patients with very high cardiovascular risk: a real-world evidence study in primary care. Atherosclerosis. 2017;263:36–41. https://doi.org/10.1016/j.atherosclerosis.2017.05.018.CrossRefGoogle Scholar