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doi:10.12788/jfp.0112

PURLs

Consider this Rx for patients with high triglycerides?

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

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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.

WHAT’S NEW

First RCT to demonstrate valueof pairing icosapent ethyl with a statin

Many prior studies on use of omega-3 fatty acid supplements to treat hypertriglyceridemia did not show any benefit, possibly due to a low dose or low ratio of EPA in the study drug.⁸ One trial (JELIS) with favorable results was an open-label study, limited to patients in Japan. The REDUCE-IT study was the first randomized, placebo-controlled trial to show that icosapent ethyl treatment for hypertriglyceridemia in patients with known CVD who are taking a statin results in fewer cardiovascular events than statin use alone.

In this multinational trial of patients with hypertriglyceridemia and CVD or cardiovascular risk factors, icosapent ethyl significantly reduced the risk of cardiovascular events.

Also worth noting: Since publication of the REDUCE-IT study, the FDA has approved an expanded indication for icosapent ethyl for reduction of risk of cardiovascular events in statin-treated patients with hypertriglyceridemia and established CVD or diabetes and ≥ 2 additional cardiovascular risk factors.¹¹

CAVEATS

Drug’s benefit was not linkedto triglyceride level reductions

The cardiovascular benefits of icosapent ethyl were obtained irrespective of triglyceride levels achieved. This raises the question of other potential mechanisms of action of icosapent ethyl in achieving cardiovascular benefit. However, this should not preclude the use of icosapent ethyl for secondary prevention in appropriate patients.

CHALLENGES TO IMPLEMENTATION

Medication is pricey

Icosapent ethyl is an expensive medication, currently priced at an estimated $351/month using a nationally available discount pharmacy plan, although additional manufacturer’s discounts may apply.^12,13 The cost of the medication could be a consideration for widespread implementation of this recommendation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

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?

References

WHAT’S NEW

First RCT to demonstrate valueof pairing icosapent ethyl with a statin

CAVEATS

Drug’s benefit was not linkedto triglyceride level reductions

CHALLENGES TO IMPLEMENTATION

Medication is pricey

Pages

Online-Only Materials

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