Access and Savings
VASCEPA is affordable for most patients*
VASCEPA is affordable for most patients*
*Data on file.
‡As of June 5, 2017.
||Premium, deductible, copay, and drug costs in the coverage gap are reduced or eliminated for LIS beneficiaries.
¶Symphony Health Claims Data; September 2017.
VASCEPA® (icosapent ethyl) is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia.
Please see full Important Safety Information, Important Disclosure Information, and Disclosures on Inflammation for HCPs about the use of VASCEPA, along with diet, as an add-on to statins in patients with high (200-499 mg/dL) TG levels below. Please see Important JELIS Information for healthcare professionals considering co-administration therapy with statins for additional lipid management in mixed dyslipidemia.
Please see full Prescribing Information for more information on VASCEPA.
The changes in the major lipoprotein lipid parameters for the groups receiving VASCEPA plus statin or placebo plus statin are shown in the table.
(Data reviewed and confirmed by the FDA—indication not approved by the FDA)
% change=median percent change from baseline.
Difference=median of (VASCEPA % change–placebo % change) (Hodges-Lehmann Estimate).
P values from Wilcoxon rank sum test.
VASCEPA significantly reduced TG, non–HDL-C, Apo B, VLDL-C, TC, and HDL-C levels from baseline relative to placebo. The reduction in TG observed with VASCEPA was not associated with elevations in LDL-C relative to placebo.
The effect of VASCEPA on cardiovascular mortality and morbidity in patients with mixed dyslipidemia has not been determined.
% change=median percent change from baseline.
Difference=median of (VASCEPA % change–placebo % change) (Hodges-Lehmann Estimate).
P values from Wilcoxon rank sum test.
Only subjects with non-missing baseline and week 12 values are included. P values for Lp-PLA2, a secondary endpoint, were adjusted for multiple comparisons; all other endpoints are exploratory. The n’s represent the number of subjects with marker samples tested in the VASCEPA 4 g/day + statin and placebo + statin treatment arms, respectively.
hsCRP=high-sensitivity C-reactive protein, ICAM-1=intercellular adhesion molecule-1, IL-6=interleukin-6, Lp-PLA2=lipoprotein-associated phospholipase A2, Ox-LDL=oxidized low-density lipoprotein
% change=median percent change from baseline.
Difference=median of (VASCEPA % change–placebo % change) (Hodges-Lehmann Estimate).
P values from Wilcoxon rank sum test.
Only subjects with non-missing baseline and week 12 values are included. P values for Lp-PLA2, a secondary endpoint, were adjusted for multiple comparisons; all other endpoints are exploratory. The n’s represent the number of subjects with marker samples tested in the VASCEPA 4 g/day and placebo treatment arms, respectively.
hsCRP=high-sensitivity C-reactive protein, ICAM-1=intercellular adhesion molecule-1, IL-6=interleukin-6, Lp-PLA2=lipoprotein-associated phospholipase A2, Ox-LDL=oxidized low-density lipoprotein
This information on inflammatory markers cannot be used in isolation. Please see additional information on the ANCHOR study above and inflammatory markers below.
JELIS was supported by grants from the manufacturer of the product, Mochida Pharmaceutical Co Ltd, Tokyo, Japan.
The product studied in JELIS and VASCEPA, are highly similar based on a US Food and Drug Administration (FDA) review of both a comprehensive analytical comparison and published reports on each product’s content. Each product is highly purified EPA. The product studied in JELIS is not available in the United States.
The highly purified EPA studied in JELIS was administered at 1.8 grams/day (g/d). VASCEPA at 4 g/d is an FDA-approved product indicated for a different use than that investigated in JELIS (see VASCEPA (icosapent ethyl) Indication and Limitations of Use above). The effect of VASCEPA on cardiovascular mortality and morbidity has not been determined. VASCEPA 4 g/d is under clinical investigation to evaluate its potential in reducing cardiovascular mortality and morbidity in a combined primary and secondary prevention (high-risk) patient population receiving statin therapy (see Ongoing cardiovascular outcomes study of VASCEPA in statin-treated patients below).
Adapted from Yokoyama et al, Figure 3: Estimated hazard ratios of clinical endpoints stratified by prevention stratum; Saito et al, Figure 3: Effects of EPA on the incidence of MCE for the high TG/low HDL-C group; Matsuzaki et al, Figure 2a: Kaplan-Meier estimates of the incidence of the primary endpoint of coronary events occurring in the group of all patients.
HR, hazard ratio.
*There was no suggestion of a difference in treatment effect between TG levels of ≥151 mg/dL (HR, 0.84; 95% Confidence Interval, 0.68-1.04) and TG levels of <151 mg/dL (HR, 0.79; 95% Confidence Interval, 0.61-1.02) when HDL-C is not considered (interaction P=0.75).
†When JELIS was conducted (over the period of 1996-2004), cholesterol management was not as aggressive as it is today for someone with established CAD. In addition, there was likely less use of antiplatelet/anticoagulant agents for someone with established CAD as there is in medical practice today.
JELIS is the only cardiovascular outcomes trial that has examined the effects of EPA (1.8 g/d) plus statin vs statin alone. The 12-week end-of-treatment blood levels after 4 g/d of EPA in an American population achieved approximately the same end-of-treatment blood levels of EPA observed in the Japanese population studied in JELIS.8 The clinical relevance of EPA blood levels on cardiovascular outcomes has not been determined.
Following JELIS and GISSI-P (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico-Prevenzione),9 randomized placebo-controlled trials have failed to confirm definitive cardiovascular benefit with similarly low (<2 g/d) doses of omega-3 fatty acid mixtures. GISSI-P is an open-label outcomes trial (1 g omega-3 fatty acid mixture), conducted in Italy, that supported the hypothesis that omega-3 fatty acids likely exert their cardioprotective effects through nonlipid-mediated mechanisms. But, in GISSI-P, only ≈5% of patients were receiving statins at baseline compared with >40%-50% in more recent, similarly low-dose omega-3 trials that failed to confirm benefit. GISSI-P did not suggest an effect on the incidence of nonfatal cardiovascular events and the effects of omega-3 fatty acids on lipids, including serum TGs, were negligible.
The omega-3 fatty acid mixtures studied in such other outcomes trials were primarily comprised of EPA and docosahexaenoic acid (DHA) (typically, approximately 900 mg total per 1 gram capsule) and also typically included a number of other omega-3 and omega-6 acids, as well as other constituents. No head-to-head cardiovascular outcomes study of EPA vs a mixture of omega-3 acids has been conducted. No cardiovascular outcomes trial has been completed with sufficient power to prospectively evaluate the effect of EPA or omega-3 fatty acid mixtures in statin-treated patients, either with high TG levels (≥200 mg/dL) or with both high TG and low HDL-C levels.
The encouraging results of JELIS contributed to the justification to investigate the potential of VASCEPA to reduce cardiovascular risk. A cardiovascular outcomes study of VASCEPA designed to evaluate the efficacy of 4 g/d of VASCEPA in reducing cardiovascular mortality and morbidity in a high-risk patient population on statin therapy is currently underway (REDUCE-IT). The sponsor of REDUCE-IT, Amarin Pharma, Inc., and the FDA are strongly aligned in recognizing the importance of continuing to collaborate to complete REDUCE-IT so that a definitive answer may be provided to answer the question of whether VASCEPA, in combination with a statin, results in reduction of cardiovascular risk over a statin alone.
Participants in the clinical investigation of VASCEPA currently underway (REDUCE-IT) should not be advised to use VASCEPA in place of participation in that study. VASCEPA should not be taken in place of a healthy diet and lifestyle or statin therapy.
References: 1. 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(7):984-992. 2. Amarin Pharma, Inc. et al v. United States Food and Drug Administration et al, 119 F. Supp. 3d. 196 (S.D.N.Y. 2015). 3. Bays HE, Ballantyne CM, Braeckman RA, Stirtan WG, Soni PN. Icosapent ethyl, a pure ethyl ester of eicosapentaenoic acid: effects on circulating markers of inflammation from the MARINE and ANCHOR studies. Am J Cardiovasc Drugs. 2013;13(1):37-46. 4. Yokoyama M, Origasa H, Matsuzaki M, et al; for the 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. Lancet. 2007;369(9567):1090-1098. 5. Saito Y, Yokoyama M, Origasa H, et al; for the JELIS Investigators, Japan. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200(1):135-140. 6. Matsuzaki M, Yokoyama M, Saito Y, et al; for the JELIS Investigators, Japan. Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease. Circ J. 2009;73(7):1283-1290. 7. Borow KM, Nelson JR, Mason RP. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis. Atherosclerosis. 2015;242(1):357-366. 8. Weintraub HS. Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014;126(7):7-18. 9. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999;354(9177):447-455.
VASCEPA® (icosapent ethyl) is indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia.
Please see full Important Safety Information, Important Disclosure Information, and Disclosures on Inflammation for HCPs about the use of VASCEPA, along with diet, as an add-on to statins in patients with high (200-499 mg/dL) TG levels below. Please see Important JELIS Information for healthcare professionals considering co-administration therapy with statins for additional lipid management in mixed dyslipidemia.
Please see full Prescribing Information for more information on VASCEPA.
The changes in the major lipoprotein lipid parameters for the groups receiving VASCEPA plus statin or placebo plus statin are shown in the table.
(Data reviewed and confirmed by the FDA—indication not approved by the FDA)
% change=median percent change from baseline.
Difference=median of (VASCEPA % change–placebo % change) (Hodges-Lehmann Estimate).
P values from Wilcoxon rank sum test.
VASCEPA significantly reduced TG, non–HDL-C, Apo B, VLDL-C, TC, and HDL-C levels from baseline relative to placebo. The reduction in TG observed with VASCEPA was not associated with elevations in LDL-C relative to placebo.
The effect of VASCEPA on cardiovascular mortality and morbidity in patients with mixed dyslipidemia has not been determined.
% change=median percent change from baseline.
Difference=median of (VASCEPA % change–placebo % change) (Hodges-Lehmann Estimate).
P values from Wilcoxon rank sum test.
Only subjects with non-missing baseline and week 12 values are included. P values for Lp-PLA2, a secondary endpoint, were adjusted for multiple comparisons; all other endpoints are exploratory. The n’s represent the number of subjects with marker samples tested in the VASCEPA 4 g/day + statin and placebo + statin treatment arms, respectively.
hsCRP=high-sensitivity C-reactive protein, ICAM-1=intercellular adhesion molecule-1, IL-6=interleukin-6, Lp-PLA2=lipoprotein-associated phospholipase A2, Ox-LDL=oxidized low-density lipoprotein
% change=median percent change from baseline.
Difference=median of (VASCEPA % change–placebo % change) (Hodges-Lehmann Estimate).
P values from Wilcoxon rank sum test.
Only subjects with non-missing baseline and week 12 values are included. P values for Lp-PLA2, a secondary endpoint, were adjusted for multiple comparisons; all other endpoints are exploratory. The n’s represent the number of subjects with marker samples tested in the VASCEPA 4 g/day and placebo treatment arms, respectively.
hsCRP=high-sensitivity C-reactive protein, ICAM-1=intercellular adhesion molecule-1, IL-6=interleukin-6, Lp-PLA2=lipoprotein-associated phospholipase A2, Ox-LDL=oxidized low-density lipoprotein
This information on inflammatory markers cannot be used in isolation. Please see additional information on the ANCHOR study above and inflammatory markers below.
JELIS was supported by grants from the manufacturer of the product, Mochida Pharmaceutical Co Ltd, Tokyo, Japan.
The product studied in JELIS and VASCEPA, are highly similar based on a US Food and Drug Administration (FDA) review of both a comprehensive analytical comparison and published reports on each product’s content. Each product is highly purified EPA. The product studied in JELIS is not available in the United States.
The highly purified EPA studied in JELIS was administered at 1.8 grams/day (g/d). VASCEPA at 4 g/d is an FDA-approved product indicated for a different use than that investigated in JELIS (see VASCEPA (icosapent ethyl) Indication and Limitations of Use above). The effect of VASCEPA on cardiovascular mortality and morbidity has not been determined. VASCEPA 4 g/d is under clinical investigation to evaluate its potential in reducing cardiovascular mortality and morbidity in a combined primary and secondary prevention (high-risk) patient population receiving statin therapy (see Ongoing cardiovascular outcomes study of VASCEPA in statin-treated patients below).
Adapted from Yokoyama et al, Figure 3: Estimated hazard ratios of clinical endpoints stratified by prevention stratum; Saito et al, Figure 3: Effects of EPA on the incidence of MCE for the high TG/low HDL-C group; Matsuzaki et al, Figure 2a: Kaplan-Meier estimates of the incidence of the primary endpoint of coronary events occurring in the group of all patients.
HR, hazard ratio.
*There was no suggestion of a difference in treatment effect between TG levels of ≥151 mg/dL (HR, 0.84; 95% Confidence Interval, 0.68-1.04) and TG levels of <151 mg/dL (HR, 0.79; 95% Confidence Interval, 0.61-1.02) when HDL-C is not considered (interaction P=0.75).
†When JELIS was conducted (over the period of 1996-2004), cholesterol management was not as aggressive as it is today for someone with established CAD. In addition, there was likely less use of antiplatelet/anticoagulant agents for someone with established CAD as there is in medical practice today.
JELIS is the only cardiovascular outcomes trial that has examined the effects of EPA (1.8 g/d) plus statin vs statin alone. The 12-week end-of-treatment blood levels after 4 g/d of EPA in an American population achieved approximately the same end-of-treatment blood levels of EPA observed in the Japanese population studied in JELIS.9 The clinical relevance of EPA blood levels on cardiovascular outcomes has not been determined.
Following JELIS and GISSI-P (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico-Prevenzione),10 randomized placebo-controlled trials have failed to confirm definitive cardiovascular benefit with similarly low (<2 g/d) doses of omega-3 fatty acid mixtures. GISSI-P is an open-label outcomes trial (1 g omega-3 fatty acid mixture), conducted in Italy, that supported the hypothesis that omega-3 fatty acids likely exert their cardioprotective effects through nonlipid-mediated mechanisms. But, in GISSI-P, only ≈5% of patients were receiving statins at baseline compared with >40%-50% in more recent, similarly low-dose omega-3 trials that failed to confirm benefit. GISSI-P did not suggest an effect on the incidence of nonfatal cardiovascular events and the effects of omega-3 fatty acids on lipids, including serum TGs, were negligible.
The omega-3 fatty acid mixtures studied in such other outcomes trials were primarily comprised of EPA and docosahexaenoic acid (DHA) (typically, approximately 900 mg total per 1 gram capsule) and also typically included a number of other omega-3 and omega-6 acids, as well as other constituents. No head-to-head cardiovascular outcomes study of EPA vs a mixture of omega-3 acids has been conducted. No cardiovascular outcomes trial has been completed with sufficient power to prospectively evaluate the effect of EPA or omega-3 fatty acid mixtures in statin-treated patients, either with high TG levels (≥200 mg/dL) or with both high TG and low HDL-C levels.
The encouraging results of JELIS contributed to the justification to investigate the potential of VASCEPA to reduce cardiovascular risk. A cardiovascular outcomes study of VASCEPA designed to evaluate the efficacy of 4 g/d of VASCEPA in reducing cardiovascular mortality and morbidity in a high-risk patient population on statin therapy is currently underway (REDUCE-IT). The sponsor of REDUCE-IT, Amarin Pharma, Inc., and the FDA are strongly aligned in recognizing the importance of continuing to collaborate to complete REDUCE-IT so that a definitive answer may be provided to answer the question of whether VASCEPA, in combination with a statin, results in reduction of cardiovascular risk over a statin alone.
Participants in the clinical investigation of VASCEPA currently underway (REDUCE-IT) should not be advised to use VASCEPA in place of participation in that study. VASCEPA should not be taken in place of a healthy diet and lifestyle or statin therapy.
References: 1. 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(7):984-992. 2.VASCEPA [package insert]. Bedminster, NJ: Amarin Pharma, Inc.; 2017. 3. Amarin Pharma, Inc. et al v. United States Food and Drug Administration et al, 119 F. Supp. 3d. 196 (S.D.N.Y. 2015). 4. Bays HE, Ballantyne CM, Braeckman RA, Stirtan WG, Soni PN. Icosapent ethyl, a pure ethyl ester of eicosapentaenoic acid: effects on circulating markers of inflammation from the MARINE and ANCHOR studies. Am J Cardiovasc Drugs. 2013;13(1):37-46. 5. Yokoyama M, Origasa H, Matsuzaki M, et al; for the 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. Lancet. 2007;369(9567):1090-1098. 6. Saito Y, Yokoyama M, Origasa H, et al; for the JELIS Investigators, Japan. Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis. 2008;200(1):135-140. 7. Matsuzaki M, Yokoyama M, Saito Y, et al; for the JELIS Investigators, Japan. Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease. Circ J. 2009;73(7):1283-1290. 8. Borow KM, Nelson JR, Mason RP. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis. Atherosclerosis. 2015;242(1):357-366. 9. Weintraub HS. Overview of prescription omega-3 fatty acid products for hypertriglyceridemia. Postgrad Med. 2014;126(7):7-18. 10. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999;354(9177):447-455.