Skip to main content

Advertisement

Log in

Dyslipidemia: Contemporary Therapy Options in Terms of Worldwide Guidelines

  • Cardiovascular Pharmacology (J Ndisang, Section Editor)
  • Published:
Current Pharmacology Reports Aims and scope Submit manuscript

Abstract

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.

Recent Findings

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.

Summary

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

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.

    CAS  PubMed  Google Scholar 

  2. Jawalekar S. The hyperlipoproteinemia - an approach to diagnosis and classification. Biochem Physiol. 2012;1:e105. https://doi.org/10.4172/2168-9652.1000e105.

    Article  Google Scholar 

  3. Sullivan D, Lewis B. A classification of lipoprotein disorders: implications for clinical management. Clin Lipidol. 2011;6(3):327–38. https://doi.org/10.2217/clp.11.24.

    Article  Google Scholar 

  4. Sniderman A, Couture P, de Graaf J. Diagnosis and treatment of apolipoprotein B dyslipoproteinemias. Nat Rev Endocrinol. 2010;6:335–46. https://doi.org/10.1038/nrendo.2010.50.

    Article  CAS  PubMed  Google Scholar 

  5. Lovic D, Stojanov V, Jakovljević B, et al. Prevalence of arterial hypertension in Serbia: PAHIS study. J Hypertens. 2013;31:2151–7.

    Article  CAS  PubMed  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.

    Article  PubMed  PubMed Central  Google 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rondanelli M, Giacosa A, Morazzoni P, Guido D, Grassi M, Morandi G, et al. MediterrAsian diet products that could raise HDL-cholesterol: a systematic review. Biomed Res Int. 2016;2025687:1–15. https://doi.org/10.1155/2016/2025687.

    Article  CAS  Google Scholar 

  10. Millar CL, Duclos Q, Blesso CN. Effects of dietary flavonoids on reverse cholesterol transport, HDL metabolism, and HDL function. Adv Nutr. 2017;8:226–39. https://doi.org/10.3945/an.116.014050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rosenson RS, Brewer HB Jr. New challenges for HDL-modifying therapies as a strategy to lower cardiovascular disease events in statin-treated patients. Cardiovasc Drugs Ther. 2015;29:1–3. https://doi.org/10.1007/s10557-015-6576-7.

    Article  PubMed  Google Scholar 

  12. Raghow R. Statins redux: a re-assessment of how statins lower plasma cholesterol. World J Diabetes. 2017;8:230–4. https://doi.org/10.4239/wjd.v8.i6.230.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Ewang-Emukowhate M, Wierzbicki AS. Lipid-lowering agents. J Cardiovasc Pharmacol Ther. 2013;18:401–11. https://doi.org/10.1177/1074248413492906.

    Article  CAS  PubMed  Google Scholar 

  14. Schulz I. Treatment of dyslipidemia: How and when to combine lipid lowering drugs. Arq Bras Endocrinol Metabol. 2006;50:344–59.

    Article  PubMed  Google 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.

    Article  Google Scholar 

  16. Lipka LJ. Ezetimibe: a first-in-class, novel cholesterol absorption inhibitor. Cardiovasc Drug Rev. 2003;21(4):293–312.

    Article  CAS  PubMed  Google Scholar 

  17. Bove M, Fogacci F, Cicero AFG. Pharmacokinetic drug evaluation of ezetimibe + simvastatin for the treatment of hypercholesterolemia. Expert Opin Drug Metab Toxicol. 2017;13:1099–104. https://doi.org/10.1080/17425255.2017.1381085.

    Article  PubMed  Google 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.

    Article  CAS  Google 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.

    Article  CAS  PubMed  Google 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.

    Article  CAS  PubMed  Google 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.

    Article  CAS  Google Scholar 

  22. Crooke ST, Geary RS. Clinical pharmacological properties of mipomersen (Kynamro), a second generation antisense inhibitor of apolipoprotein B. Br J Clin Pharmacol. 2013;76:269–76. https://doi.org/10.1111/j.1365-2125.2012.04469.x.

    Article  CAS  PubMed  Google Scholar 

  23. Ricotta DN, Frishman W. Mipomersen: a safe and effective antisense therapy adjunct to statins in patients with hypercholesterolemia. Cardiol Rev. 2012;20:90–5. https://doi.org/10.1097/CRD.0b013e31823424be.

    Article  PubMed  Google 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.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Leigh SE, Foster AH, Whittall RA, Hubbart CS, Humphries SE. Update and analysis of the University College London low density lipoprotein receptor familial hypercholesterolemia database. Ann Hum Genet. 2008;72:485–98. https://doi.org/10.1111/j.1469-1809.2008.00436.x.

    Article  CAS  PubMed  Google Scholar 

  26. Wang Y, Huang Y, Hobbs HH, Cohen JC. Molecular characterization of proprotein convertase subtilisin/kexin type 9-mediated degradation of the LDLR. J Lipid Res. 2012;53:1932–43. https://doi.org/10.1194/jlr.M028563.

    Article  CAS  PubMed  PubMed Central  Google 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.

    Article  CAS  Google Scholar 

  28. Ai D, Chen C, Han S, Ganda A, Murphy AJ, Haeusler R, et al. Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice. J Clin Invest. 2012;122(4):1262–70. https://doi.org/10.1172/JCI61919.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tang Z, Jiang L, Peng J, Ren Z, Wei D, Wu C, et al. PCSK9 siRNA suppresses the inflammatory response induced by oxLDL through inhibition of NF-κB activation in THP-1-derived macrophages. Int J Mol Med. 2012;30:931–8. https://doi.org/10.3892/ijmm.2012.1072.

    Article  CAS  PubMed  Google 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.

    Article  CAS  PubMed  Google Scholar 

  31. Lovic D, Erdine S, Burak Çatakoǧlu A. How to estimate left ventricular hypertrophy in hypertensive patients. Anadolu Kardiyoli Derg. 2014;14:389–95.

    Article  Google Scholar 

  32. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–22. https://doi.org/10.1056/NEJMoa1615664.

    Article  CAS  Google Scholar 

  33. Ridker PM, Revkin J, Amarenco P, Brunell R, Curto M, Civeira F, et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med. 2017;376:1527–39. https://doi.org/10.1056/NEJMoa1701488.

    Article  CAS  Google Scholar 

  34. Ray KK, Landmesser U, Leiter LA, Kallend D, Dufour R, Karakas M, et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N Engl J Med. 2017;376:1430–40. https://doi.org/10.1056/NEJMoa1615758.

    Article  CAS  Google Scholar 

  35. Zhang Y, Eigenbrot C, Zhou L, Shia S, Li W, Quan C, et al. Identification of a small peptide that inhibits PCSK9 protein binding to the low density lipoprotein receptor. J Biol Chem. 2014;289(2):942–55. https://doi.org/10.1074/jbc.M113.514067.

    Article  CAS  PubMed  Google 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.

    Article  Google Scholar 

  37. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman JM, Drexel H, et al. 2016 ESC/EAS guidelines for the management of dyslipidemias. Eur Heart J. 2016;37:2999–3058. https://doi.org/10.1093/eurheartj/ehx180.

    Article  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google Scholar 

  40. Chou R, Dana T, Blazina I, Daeges M, Jeanne TL. Statins for prevention of cardiovascular disease in adults: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2016;316:2008–24. https://doi.org/10.1001/jama.2015.15629.

    Article  PubMed  Google Scholar 

  41. Downs JR, O'Malley PG. Management of dyslipidemia for cardiovascular disease risk reduction: synopsis of the 2014 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline. Ann Intern Med. 2015;163:291–7. https://doi.org/10.7326/M15-0840.

    Article  PubMed  Google Scholar 

  42. Tibrewala A, Jivan A, Oetgen WJ, Stone NJ. A comparative analysis of current lipid treatment guidelines: nothing stands still. J Am Coll Cardiol. 2018;71:794–9. https://doi.org/10.1016/j.jacc.2017.12.025.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Lovic D, Narayan P, Pittaras A, et al. Left ventricular hypertrophy in athletes and hypertensive patients. J Clin Hypertens (Greenwich). 2017;19:413–7.

    Article  Google Scholar 

  47. Boekholdt SM, Hovingh GK, Mora S, Arsenault BJ, Amarenco P, Pedersen TR, et al. Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials. J Am Coll Cardiol. 2014;64:485–94. https://doi.org/10.1016/j.jacc.2014.02.615.

    Article  CAS  PubMed  PubMed Central  Google 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.

    Article  CAS  PubMed  Google 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.

    Article  CAS  PubMed  PubMed Central  Google 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.

    Article  CAS  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  CAS  PubMed  Google Scholar 

  53. Lin I, Sung J, Sanchez RJ, Mallya UG, Friedman M, Panaccio M, et al. Patterns of statin use in a real-wold population of patients at high cardiovascular risk. J Manag Care Spec Pharm. 2016;22(6):685–98. https://doi.org/10.18553/jmcp.2016.22.6.685.

    Article  PubMed  Google 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.

  55. Cannon CP, Blazing MA, Giugliano RP, IMPROVE-IT investigators, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387–97. https://doi.org/10.1056/NEJMoa1410489.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  57. Robinson JG, Farnier M, Krempf M, ODYSSEY long-term investigators, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1489–99. https://doi.org/10.1056/NEJMoa1501031.

    Article  CAS  Google Scholar 

  58. The ILLUMINATE Investigators. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–22. https://doi.org/10.1056/NEJMoa0706628.

    Article  Google Scholar 

  59. Schwartz GG, Olsson AG, Abt M, dal-OUTCOMES Investigators, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367:2089–99. https://doi.org/10.1056/NEJMoa1206797.

    Article  CAS  Google Scholar 

  60. Lovic D, Pittaras A, Kallistratos M, et al. Sodium-glucose cotransporter 2 inhibitors: potential cardiovascular and mortality benefits. Cardiovasc Hematol Disord Drug Targets. 2018;18:114–9.

    Article  CAS  PubMed  Google 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.

    Article  CAS  PubMed  Google Scholar 

  62. Wu Q, Tang ZH, Peng J, Liao L, Pan LH, Wu ZY, et al. The dual behavior of PCSK9 in the regulation of apoptosis is crucial in Alzheimer’s disease progression (review). Biomed Rep. 2014;2(2):167–71. https://doi.org/10.3892/br.2013.213.

    Article  CAS  PubMed  Google 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.

    Article  PubMed  Google Scholar 

  64. Kysenius K, Muggalla P, Mätlik K, Arumäe U, Huttunen HJ. PCSK9 regulates neuronal apoptosis by adjusting ApoER2 levels and signaling. Cell Mol Life Sci. 2012;69:1903–16. https://doi.org/10.1007/s00018-012-0977-6.

    Article  CAS  PubMed  Google Scholar 

  65. Blom DJ, Djedjos S, Monsalvo ML, et al. Effects of evolocumab on vitamin E and steroid hormone levels. Circ Res. 2015;117:731–41. https://doi.org/10.1161/CIRCRESAHA.115.307071.

    Article  CAS  PubMed  Google Scholar 

  66. Robinson JG, Rosenson RS, Farnier M, et al. Safety of very low low-density lipoprotein cholesterol levels with alirocumab: pooled data from randomized trials. J Am Coll Cardiol. 2017;69:471–82. https://doi.org/10.1016/j.jacc.2016.11.037.

    Article  CAS  PubMed  Google 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.

    Article  CAS  Google Scholar 

  68. Varbo A, Benn M, Tybjaerg-Hansen A, Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol. 2013;61:427–36. https://doi.org/10.1016/j.jacc.2012.08.1026.

    Article  CAS  Google 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.

    Article  CAS  PubMed  Google 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.

    Article  CAS  PubMed  PubMed Central  Google 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.

    Article  PubMed  Google Scholar 

  72. HPS2-THRIVE Collaborative Group, Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371:203–12. https://doi.org/10.1056/NEJMoa1300955.

    Article  CAS  Google Scholar 

  73. Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, et al. Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ. 2006;332:752–60. https://doi.org/10.1136/bmj.38755.366331.2F.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Rosenson RS, Davidson MH, Katheserin S, Hirsh B, Gaudet D. Triglyceride-rich lipoproteins and atherosclerosis. J Am Coll Cardiol. 2014;64:2525–40. https://doi.org/10.1016/j.jacc.2014.09.042.

    Article  CAS  PubMed  Google Scholar 

  75. Rosenson RS, Underberg JA. Systematic review: evaluating the effect of lipid-lowering therapy on lipoprotein and lipid value. Cardiovasc Drugs Ther. 2013;27:465–79. https://doi.org/10.1007/s10557-013-6477-6.

    Article  CAS  PubMed  PubMed Central  Google 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.

    Article  CAS  PubMed  Google Scholar 

  77. Nicholls SJ, Tuzcu EM, Sipahi I, Grasso AW, Schoenhagen P, Hu T, et al. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. 2007;297:499–508. https://doi.org/10.1001/jama.2975.499.

    Article  CAS  Google Scholar 

  78. Naderi SH, Bestwick JP, Wald DS. Adherence to drugs that prevent cardiovascular disease: meta-analysis on 376,162 patients. Am J Med. 2012;125:882–887.e1. https://doi.org/10.1016/j.amjmed.2011.12.013.

    Article  PubMed  Google 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.

    Article  CAS  PubMed  Google Scholar 

  81. Michie S, van Stralen MM, West R. The behaviour change wheel: a new method for characterising and designing behaviour change interventions. Implement Sci. 2011;6:42. https://doi.org/10.1186/1748-5908-6-42.

    Article  PubMed  PubMed Central  Google Scholar 

  82. Bosworth HB, Granger BB, Mendys P, Brindis R, Burkholder R, Czajkowski SM, et al. Medication adherence: a call for action. Am Heart J. 2011;162:412–24. https://doi.org/10.1016/j.ahj.2011.06.007.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We hereby thank Jasmina Nedeljkovic for providing language and proofreading assistance during the creation of this paper.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dragan B. Djordjevic.

Ethics declarations

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.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Cardiovascular Pharmacology

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Djordjevic, D.B., Dordevic, A.D. & Lovic, D.B. Dyslipidemia: Contemporary Therapy Options in Terms of Worldwide Guidelines. Curr Pharmacol Rep 5, 87–97 (2019). https://doi.org/10.1007/s40495-019-00173-w

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40495-019-00173-w

Keywords

Navigation