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doi:10.12788/jfp.0112

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Consider this Rx for patients with high triglycerides?

J Fam Pract. 2020 December;69(10):518-525 | 10.12788/jfp.0112

By

Kyle Leggott, MD

Corey Lyon, DO

Liza Claus, PharmD, BCACP

A daily dose of this prescription fish oil may be worth a trial in light of the cardiovascular benefits it affords statin-treated patients with high triglycerides.

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PRACTICE CHANGER

Consider icosapent ethyl, 2 g twice daily, for secondary prevention of adverse cardiovascular events in patients with elevated triglycerides who are already taking a statin.

STRENGTH OF RECOMMENDATION

B: Based on a single, good-quality, multicenter, randomized controlled trial. Bhatt DL, Steg PG, Miller M, et al; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.1

Bhatt DL, Steg PG, Miller M, et al; REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.1

References

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

2. Bhatt DL, Eagle KA, Ohman EM, et al; REACH Registry Investigators. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA. 2010;304:1350-1357.

3. Cannon CP, Braunwald E, McCabe CH, et al; Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes [published correction appears in N Engl J Med. 2006;354:778]. N Engl J Med. 2004;350:1495-1504.

4. Klempfner R, Erez A, Sagit BZ, et al. Elevated triglyceride level is independently associated with increased all-cause mortality in patients with established coronary heart disease: twenty-two-year follow-up of the Bezafibrate Infarction Prevention Study and Registry [published correction appears in Circ Cardiovasc Qual Outcomes. 2016;9:613]. Circ Cardiovasc Qual Outcomes. 2016;9:100-108.

5. Nichols GA, Philip S, Reynolds K, Granowitz CB, Fazio S. Increased cardiovascular risk in hypertriglyceridemic patients with statin-controlled LDL cholesterol. J Clin Endocrinol Metab. 2018;103:3019-3027.

6. Grundy SM, Stone NJ, Bailey AL, 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 [published correction appears in J Am Coll Cardiol. 2019;73:3237-3241]. J Am Coll Cardiol. 2019;73:e285-e350.

7. Ganda OP, Bhatt DL, Mason RP, Miller M, Boden WE. Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management. J Am Coll Cardiol. 2018;72:330-343.

8. Aung T, Halsey J, Kromhout D, 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;3:225-234.

9. Yokoyama M, Origasa H, Matsuzaki M, et al; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis [published correction appears in Lancet. 2007;370:220]. Lancet. 2007;369:1090-1098.

10. Ballantyne CM, Bays HE, Kastelein JJ, et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-992.

11. FDA approves use of drug to reduce risk of cardiovascular events in certain adult patient groups [news release]. Silver Spring, MD: US Food and Drug Administration; December 13, 2019. www.fda.gov/news-events/press-announcements/fda-approves-use-drug-reduce-risk-cardiovascular-events-certain-adult-patient-groups. Accessed November 30, 2020.

12. Vascepa. GoodRx. www.goodrx.com/vascepa. Accessed November 30, 2020.

13. The VASCEPA Savings Program. www.vascepa.com/getting-started/savings-card/. Accessed November 30, 2020.

ILLUSTRATIVE CASE

A 63-year-old man with a medical history significant for myocardial infarction (MI) 5 years ago presents to you for an annual exam. His medications include a daily aspirin, angiotensin-converting enzyme inhibitor, beta-blocker, and a high-intensity statin for coronary artery disease (CAD). On his fasting lipid panel, his low-density lipoprotein (LDL) level is 70 mg/dL, but his triglycerides remain elevated at 200 mg/dL despite dietary changes.

In addition to lifestyle modifications, what can be done to reduce his risk of another MI?

Patients with known cardiovascular disease (CVD) or multiple risk factors for CVD are at high risk of cardiovascular events, even when taking primary or secondary preventive medications such as statins.^2,3 In these patients, elevated triglycerides are an independent risk factor for increased rates of cardiovascular events.^4,5

The 2018 American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the treatment of blood cholesterol recommend statin therapy for moderate (175-499 mg/dL) to severe (≥ 500 mg/dL) hypertriglyceridemia in appropriate patients with atherosclerotic CVD risk ≥ 7.5%, after appropriately addressing secondary causes of hypertriglycidemia.⁶

Previous studies have shown no benefit from combination therapy with triglyceride-lowering medications (eg, extended-release niacin and fibrates) and statins, compared with statin monotherapy.⁷ A recent meta-analysis concluded that omega-3 fatty acid supplements offer no reduction in cardiovascular morbidity or mortality, whether taken with or without statins.⁸

Interestingly, the randomized controlled Japan EPA Lipid Intervention Study (JELIS) demonstrated fewer major coronary events in patients with elevated cholesterol, with or without CAD, who took eicosapentaenoic acid (EPA)—a subtype of omega-3 fatty acids—plus a statin, compared with statin monotherapy.⁹

The REDUCE-IT trial evaluated icosapent ethyl, a highly purified EPA that has been shown to reduce triglycerides and, at the time this study was conducted, was approved for use solely for the reduction of triglyceride levels in adults with severe hypertriglyceridemia.^10,11

Continue to: Study Summary

References

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

2. Bhatt DL, Eagle KA, Ohman EM, et al; REACH Registry Investigators. Comparative determinants of 4-year cardiovascular event rates in stable outpatients at risk of or with atherothrombosis. JAMA. 2010;304:1350-1357.

3. Cannon CP, Braunwald E, McCabe CH, et al; Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes [published correction appears in N Engl J Med. 2006;354:778]. N Engl J Med. 2004;350:1495-1504.

4. Klempfner R, Erez A, Sagit BZ, et al. Elevated triglyceride level is independently associated with increased all-cause mortality in patients with established coronary heart disease: twenty-two-year follow-up of the Bezafibrate Infarction Prevention Study and Registry [published correction appears in Circ Cardiovasc Qual Outcomes. 2016;9:613]. Circ Cardiovasc Qual Outcomes. 2016;9:100-108.

5. Nichols GA, Philip S, Reynolds K, Granowitz CB, Fazio S. Increased cardiovascular risk in hypertriglyceridemic patients with statin-controlled LDL cholesterol. J Clin Endocrinol Metab. 2018;103:3019-3027.

6. Grundy SM, Stone NJ, Bailey AL, 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 [published correction appears in J Am Coll Cardiol. 2019;73:3237-3241]. J Am Coll Cardiol. 2019;73:e285-e350.

7. Ganda OP, Bhatt DL, Mason RP, Miller M, Boden WE. Unmet need for adjunctive dyslipidemia therapy in hypertriglyceridemia management. J Am Coll Cardiol. 2018;72:330-343.

8. Aung T, Halsey J, Kromhout D, 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;3:225-234.

9. Yokoyama M, Origasa H, Matsuzaki M, et al; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis [published correction appears in Lancet. 2007;370:220]. Lancet. 2007;369:1090-1098.

10. Ballantyne CM, Bays HE, Kastelein JJ, et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110:984-992.

11. FDA approves use of drug to reduce risk of cardiovascular events in certain adult patient groups [news release]. Silver Spring, MD: US Food and Drug Administration; December 13, 2019. www.fda.gov/news-events/press-announcements/fda-approves-use-drug-reduce-risk-cardiovascular-events-certain-adult-patient-groups. Accessed November 30, 2020.

12. Vascepa. GoodRx. www.goodrx.com/vascepa. Accessed November 30, 2020.

13. The VASCEPA Savings Program. www.vascepa.com/getting-started/savings-card/. Accessed November 30, 2020.

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Consider this Rx for patients with high triglycerides?

PRACTICE CHANGER

STRENGTH OF RECOMMENDATION

References

ILLUSTRATIVE CASE

Pages

Online-Only Materials

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