Cardiometabolic Chronicle

Residual CVD Risk: Can you REDUCE-IT?

Residual Risk: Beyond LDL-C Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death in the United States, and its prevention and treatment continue to be an area of utmost importance.1 Elevated low-density lipoprotein cholesterol (LDL-C) is a well-established ASCVD risk factor and significant advances have been made to lower it by using established and new strategies, including statin therapy, ezetimibe, and PCSK9 inhibitors.2,3 However, while lowering LDL cholesterol (LDL-C) remains central in the prevention and treatment of ASCVD, residual risk may be present even after the optimization of LDL-C levels.4

Current therapies that primarily target LDL-C may not address other drivers of atherosclerosis, including triglycerides (TGs), which seem to be part of the causal pathway in high-risk patients.2 In certain high-risk patients, including those with pre-existing ASCVD, or that have type 2 diabetes and/or metabolic syndrome, intensive treatment with statins and newer therapies to lower LDL-C may not address the full spectrum of cardiovascular prevention.4 In these patients, the interplay between phenotypes that promote both a proinflammatory state and atherogenic dyslipidemia (including elevated TG levels), requires additional measures to optimize both primary and secondary ASCVD prevention.2,4

  1. Lloyd-Jones, Donald M., 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.” Journal of the American College of Cardiology 68.1 (2016): 92-125.
  2. Bhatt, Deepak L. “REDUCE-IT: residual cardiovascular risk in statin-treated patients with elevated triglycerides: now we can REDUCE-IT!.” European Heart Journal 40.15 (2019): 1174-1175.
  3. Grundy, Scott M., et al. “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 139 (2019): e1082-e1143.
  4. Ganda, Om P., et al. “Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management.” Journal of the American College of Cardiology 72.3 (2018): 330-343.
  5. Bhatt, Deepak L., et al. “Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia.” New England Journal of Medicine 380.1 (2019): 11-22.
  6. Bhatt, Deepak L., et al. “Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT.” Journal of the American College of Cardiology 73.22 (2019): 2791-2802.
  7. Eckel, Robert H. “What is it about very low density lipoproteins (VLDL) and cardiovascular disease in patients with type 2 diabetes mellitus: Is it the triglycerides or the cholesterol?.” Atherosclerosis 237.1 (2014): 138-139.
  8. Nichols, Gregory A., et al. “Increased cardiovascular risk in patients with statin-controlled LDL cholesterol and residual hypertriglyceridemia.” Circulation 136.suppl_1 (2017): A14161-A14161.
  9. Toth, Peter, et al. “High triglycerides and ASCVD are significant predictors of major CV events and increased costs in statin-treated patients: real-world analysis.” Journal of Clinical Lipidology 12.2 (2018): 528-529.
  10. Fruchart, Jean-Charles, et al. “The Residual Risk Reduction Initiative: a call to action to reduce residual vascular risk in patients with dyslipidemia.” The American Journal of Cardiology 102.10 (2008): 1K-34K.
  11. Bays, Harold E., et al. “Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications.” Expert Review of Cardiovascular Therapy 6.3 (2008): 391- 409.
  12. Ballantyne, Christie M., Rene A. Braeckman, and Paresh N. Soni. “Icosapent ethyl for the treatment of hypertriglyceridemia.” Expert Opinion on Pharmacotherapy 14.10 (2013): 1409-1416.
  13. Ito, Matthew K. “A comparative overview of prescription omega-3 fatty acid products.” Pharmacy and Therapeutics 40.12 (2015): 826 - 836.
  14. Weintraub, Howard S. “Overview of prescription omega-3 fatty acid products for hypertriglyceridemia.” Postgraduate Medicine 126.7 (2014): 7-18.
  15. Kapoor K, et al. Patients with Very High Triglycerides and Treatment with Omega-3s. American College of Cardiology. February 2, 2016. Accessed May 8, 2019.
  16. Backes, James, et al. “The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia.” Lipids in Health and Disease 15.1 (2016): 118.
  17. Ballantyne, Christie M., et al. “Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study).” The American Journal of Cardiology 110.7 (2012): 984-992.
  18. Bays, Harold E., et al. “Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial).” The American Journal of Cardiology 108.5 (2011): 682-690.
  19. Abbasi, Jennifer. “Another nail in the coffin for fish oil supplements.” JAMA 319.18 (2018): 1851- 1852.
  20. Aung, Theingi, et al. “Associations of omega-3 fatty acid supplement use with cardiovascular disease risks: meta-analysis of 10 trials involving 77 917 individuals.” JAMA Cardiology 3.3 (2018): 225-234.
  21. Yokoyama, Mitsuhiro, et al. “Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.” The Lancet 369.9567 (2007): 1090-1098.
  22. ASCEND Study Collaborative Group. “Effects of n− 3 fatty acid supplements in diabetes mellitus.” New England Journal of Medicine 379 (2018): 1540-1550.
  23. Orringer, Carl E. “Icosapent ethyl: where will it fit into guideline-based medical therapy for high risk atherosclerotic cardiovascular disease?” Trends in Cardiovascular Medicine (2019).
  24. American Diabetes Association. “American Diabetes Association® issues critical updates to the 2019 standards of medical care in diabetes.” March 27, 2019, available at http://www.diabetes. org/newsroom/press-releases/2019/ada-issuescritical-updates-to-2019-standards-of-care.html, accessed August 6, 2019.


Sign up to receive updates on educational opportunities, complimentary content, exclusive discounts, and more.