Skip to main content

Advertisement

SpringerLink
Log in

Role of Non-Statins, LDL-C Thresholds, and Special Population Considerations: A Look at the Updated 2016 ACC Consensus Committee Recommendations

  • STATIN DRUGS (B. WIGGINS, SECTION EDITOR)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The 2013 ACC/AHA Cholesterol guidelines was a major paradigm shift in the management and treatment of dyslipidemia. The new guidelines outlined “statin benefit groups,” highlighted weighing the benefit versus risks of statin therapy (“net benefit”), and discussed the importance of shared decision making between patients and providers in primary prevention. While there was widespread agreement on the main groups benefiting from statin therapy, there was significant controversy regarding LDL-C goals and thresholds, the role of non-statin therapy, and the use of statins in specific populations. The goal of this review is to understand the rationale for the updated 2016 ACC Expert Consensus on Non-Statins and to contrast it with the 2015 NLA Recommendations on the Management of Dyslipidemia.

Recent Findings

The findings of the ACC Expert Consensus Panel were largely influenced by the results of several new clinical trials using non-statin therapy in combination with moderate to high intensity statin therapy. The IMPROVE-IT trial demonstrated that ezetimibe on top of statin therapy lowered ASCVD risk in patients with acute coronary syndromes whose LDL was driven below the previous LDL-C target of <70 mg/dL. In addition, preliminary data assessing the safety of evolocumab and alirocumab on top of statin therapy suggested possible large reductions in ASCVD risk in post hoc analysis.

Summary

Both the 2016 ACC Consensus Recommendations and the 2015 NLA Recommendations emphasize the importance of maximally tolerated statin therapy, the use of adjunctive non-statin LDL lowering therapy, and the use of LDL-C goals and thresholds to guide intensification of LDL lowering therapy. Although there are some important differences between the ACC Consensus and NLA recommendations in terms of treatment of special populations (i.e., CHF) and on the use of non-HDL-C goals and thresholds, both guidelines support a role for ezetimibe, bile acid sequestrants, and PCSK-9 inhibitors in patients on maximum tolerated statin therapy. The recent positive results of the FOURIER trial gives additional support to the non-statin recommendations of both the ACC and NLA.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Robinson JG, Stone NJ. The 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular disease risk: a new paradigm supported by more evidence. Eur Heart J. 2015;36(31):2110–8. This article summarizes the 2013 ACC/AHA guidelines on lipid management and how it represents a paradigm shift from prior guidelines. It also introduces new evidence and the rationale for some of the controversies of the 2013 ACC/AHA guideline

    Article  PubMed  Google Scholar 

  2. • Adhyaru BB, Jacobson TA. New cholesterol guidelines for the management of atherosclerotic cardiovascular disease risk: a comparison of the 2013 American College of Cardiology/American Heart Association cholesterol guidelines with the 2014 National Lipid Association recommendations for patient-centered management of dyslipidemia. Cardiol Clin. 2015;33(2):181–96. This article highlights some of the important differences in the NLA and ACC/AHA guidelines

    Article  PubMed  Google Scholar 

  3. •• Lloyd-Jones DM, Morris PB, Ballantyne CM, 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(1):92–125. This ACC consensus document summarizes in detail the recommendations of the ACC based on new clinical trial evidence and highlights the role of LDL-C thresholds as well as special populations. Also, it gives advice on the use of the nonstatins, including ezetimibe, bile acid sequestrants, PCSK9 inhibitors, and niacin. In addition, it offers a pragmatic approach to lipid management, and gives guidance to clinicians when the evidence base is incomplete

    Article  PubMed  Google Scholar 

  4. Orringer CE, Morris PB. Consensus between the American College of Cardiology and the National Lipid Association on the use of non-statin therapy for atherosclerotic cardiovascular disease prevention. J Clin Lipidol. 2016;10(3):458–61.

    Article  PubMed  Google Scholar 

  5. • Jacobson TA, Ito MK, Maki KC, et al. National lipid association recommendations for patient-centered management of dyslipidemia: part 1—full report. J Clin Lipidol. 2015;9(2):129–69. 2015 Part 1 Recommendations of the National Lipid Association after publication of the 2013 ACC/AHA Cholesterol Guidelines. Emphasizes the importantce of patient centered care, the use of LDL and Non-HDL-C goals and targets, the use of nonstatins in further reducing LDL-C and ASCVD risk, the importance of LDL-C monitoring to assess the adequacy of the response to therapy, adherence to therapy, and to provide a monitoring metric that both patients and providers understand

    Article  PubMed  Google Scholar 

  6. •• Jacobson TA, Maki KC, Orringer CE, et al. National Lipid Association Recommendations for patient-centered management of dyslipidemia: part 2. J Clin Lipidol. 2015;9(6 Suppl):S1-122–e121. The Part 2 Recommendations of the NLA includes in depth recommendations about nutrition and lifestyle; management of cholesterol and ASCVD risk throughout the lifespan (pediatrics, adolescents, pregnancy, women, and elderly); special populations including those of different ethnicities (Hispanic, African American, South Asian, and Native Indian); populations at high ASCVD risk including HIV, RA, and CKD; team based collaborative care; and methods to improve adherence to therapies

    Google Scholar 

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

    Article  Google Scholar 

  8. AIM HIGH Investigators, Boden WE, Probstfield JL, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–67.

    Article  Google Scholar 

  9. ACCORD Study Group, Ginsberg HN, Elam MB, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–74.

    Article  Google Scholar 

  10. •• Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–97. This landmark study is the first study to show a positive effect of adding non-statin therapy (ezetimibe) to moderate to high intensity statin therapy on ASCVD risk reduction.

    Article  CAS  PubMed  Google Scholar 

  11. Blazing MA, Giugliano RP, de Lemos JA, et al. On-treatment analysis of the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT). Am Heart J. 2016;182(182):89–96

  12. Jarcho JA, Keaney JF. Proof that lower is better—LDL cholesterol and IMPROVE-IT. New Engl J Med. 2015;372(25):2448, 13–50.

  13. • Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1500–9. This landmark short-term safety study shows that the PCSK-9 inhibitor evolocumab is safe and has a potential important role in ASCVD risk reduction.

    Article  CAS  PubMed  Google Scholar 

  14. • 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(16):1489–99. This landmark short-term study shows that the PCSK-9 inhibitor alirocumab is safe and has a potential important role in ASCVD risk reduction

    Article  CAS  PubMed  Google Scholar 

  15. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med 2017;376:1713–1722

  16. Aggarwal S, Loomba RS, Arora RR. Efficacy of colesevelam on lowering glycemia and lipids. J Cardiovasc Pharmacol. 2012;59(2):198–205.

    Article  CAS  PubMed  Google Scholar 

  17. Rader DJ, Kastelein JJ. Lomitapide and mipomersen: two first-in-class drugs for reducing low-density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia. Circulation. 2014;129(9):1022–32.

    Article  PubMed  Google Scholar 

  18. Bhoj VG, Sachais BS. Lipoprotein apheresis. Current Atherosclerosis Reports. 2015;17(7):39.

    Article  PubMed  Google Scholar 

  19. Gidding SS, Champagne MA, de Ferranti SD, et al. The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association. Circulation. 2015;132(22):2167–92.

    Article  PubMed  Google Scholar 

  20. Goldberg AC, Hopkins PN, Toth PP, et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on familial hypercholesterolemia. J Clin Lipidol. 2011;5(3):133–40.

    Article  PubMed  Google Scholar 

  21. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–207.

    Article  CAS  PubMed  Google Scholar 

  22. Ridker PM, Mora S, Rose L, Group JTS. Percent reduction in LDL cholesterol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents. Eur Heart J. 2016;37(17):1373–9.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lipid Research Clinics Program. JAMA. 1984;252(18):2545–8.

    Google Scholar 

  24. Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8(6):1245–55.

    Article  CAS  PubMed  Google Scholar 

  25. Expert Panel on Detection E. Treatment of high blood cholesterol in A. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001, 285;(19):2486–97.

  26. Robinson JG, Ray K. Counterpoint: low-density lipoprotein cholesterol targets are not needed in lipid treatment guidelines. Arterioscler Thromb Vasc Biol. 2016;36(4):586–90.

    Article  CAS  PubMed  Google Scholar 

  27. Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9645):1231–9.

    Article  PubMed  Google Scholar 

  28. Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357(22):2248–61.

    Article  CAS  PubMed  Google Scholar 

  29. Kjekshus J, Dunselman P, Blideskog M, et al. A statin in the treatment of heart failure? Controlled rosuvastatin multinational study in heart failure (CORONA): study design and baseline characteristics. Eur J Heart Fail. 2005;7(6):1059–69.

    Article  CAS  PubMed  Google Scholar 

  30. Takano H, Mizuma H, Kuwabara Y, et al. Effects of pitavastatin in Japanese patients with chronic heart failure: the pitavastatin heart failure study (PEARL study). Circulation Journal: Official Journal of the Japanese Circulation Society. 2013;77(4):917–25.

    Article  CAS  Google Scholar 

  31. Feinstein MJ, Jhund P, Kang J, et al. Do statins reduce the risk of myocardial infarction in patients with heart failure? A pooled individual-level reanalysis of CORONA and GISSI-HF. Eur J Heart Fail. 2015;17(4):434–41.

    Article  CAS  PubMed  Google Scholar 

  32. Preiss D, Campbell RT, Murray HM, et al. The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials. Eur Heart J. 2015;36(24):1536–46.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Kjekshus J. Are statins failing in heart failure? Eur Heart J. 2015;36(24):1502–4.

    Article  PubMed  Google Scholar 

  34. Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:1223–1230.

  35. Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (study of heart and renal protection): a randomised placebo-controlled trial. Lancet. 2011;377(9784):2181–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Fellstrom BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360(14):1395–407.

    Article  CAS  PubMed  Google Scholar 

  37. 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.

Download references

Author information

Authors and Affiliations

  1. Division of General Internal Medicine & Geriatrics, Department of Medicine, Emory University School of Medicine, 49 Jesse Hill Jr Dr, Atlanta, GA, 30303, USA

    Bhavin B. Adhyaru

  2. Lipid Clinic and Cardiovascular Risk Reduction Program, Department of Medicine, Emory University School of Medicine, 49 Jesse Hill Jr Dr, Atlanta, GA, 30303, USA

    Terry A. Jacobson

Authors
  1. Bhavin B. Adhyaru
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Terry A. Jacobson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bhavin B. Adhyaru.

Ethics declarations

Conflict of Interest

Bhavin B. Adhyaru declares no conflicts of interest.

Terry A. Jacobson is a consultant for Amarin, Amgen, Astra-Zeneca, Merck, and Regeneron/Sanofi.

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

This article is part of the Topical Collection on Statin Drugs

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Adhyaru, B.B., Jacobson, T.A. Role of Non-Statins, LDL-C Thresholds, and Special Population Considerations: A Look at the Updated 2016 ACC Consensus Committee Recommendations. Curr Atheroscler Rep 19, 29 (2017). https://doi.org/10.1007/s11883-017-0666-x

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11883-017-0666-x

Keywords

Search

Navigation