Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
A Retrospective Case Series of the Lipid Effects of Switching From Omega-3 Fatty Acid Ethyl Esters to Icosapent Ethyl in Hyperlipidemic Patients Richard S. Castaldo MD To cite this article: Richard S. Castaldo MD (2014) A Retrospective Case Series of the Lipid Effects of Switching From Omega-3 Fatty Acid Ethyl Esters to Icosapent Ethyl in Hyperlipidemic Patients, Postgraduate Medicine, 126:3, 268-273 To link to this article: http://dx.doi.org/10.3810/pgm.2014.05.2775
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A Retrospective Case Series of the Lipid Effects of Switching From Omega-3 Fatty Acid Ethyl Esters to Icosapent Ethyl in Hyperlipidemic Patients
DOI: 10.3810/pgm.2014.05.2775
Richard S. Castaldo, MD Niagara Falls Memorial Medical Center, River Road Primary Care Center, North Tonawanda, NY
Abstract
Background: Western New York is among the regions with the highest rate of heart disease and stroke in the United States. Multifactorial causes include hypertriglyceridemia and dyslipidemia, and additional therapies may be needed to reduce residual risk that remains even after treatment with statins or other lipid-lowering medications. The purpose of this study was to evaluate the effects of a switch from omega-3 fatty acid ethyl esters (OM3EE) to icosapent ethyl (IPE) on lipid profiles in patients with hyperlipidemia. Methods: This was a retrospective chart review of patient records extracted from multiple medical practices throughout Western New York (4 locations). Randomly selected patients (N = 15) were eligible if they were aged $ 18 years with diagnosis codes for high triglyceride (TG) levels or hyperlipidemia and were receiving OM3EE. They were switched from OM3EE to IPE, and lipid parameters were measured after $ 2 months. Results: The records of 15 patients were analyzed and lipid measurements were available for 14 patients; 10 were on statins and 4 were on ezetimibe. At $ 2 months after the switch to IPE, 13 patients experienced decreases in total cholesterol (TC) and non–high-density lipoprotein cholesterol (non–HDL-C) levels; 12 experienced a decrease in TG and low-density lipoprotein cholesterol (LDL-C) levels; and changes in HDL-C levels were varied, with no change in 1 patient, decreases in 9 patients, and increases in 4 patients. Conclusion: The results of this real-world retrospective analysis of 14 patients with hyperlipidemia demonstrated reductions in TG, LDL-C, TC, and non–HDL-C levels, with mixed results in HDL-C levels, after switching from OM3EE to IPE. Keywords: eicosapentaenoic acid; hypertriglyceridemia; hyperlipidemia; omega-3 fatty acids; low-density lipoprotein cholesterol; triglycerides; Lovaza; Vascepa
Introduction
Correspondence: Richard S. Castaldo, MD, Internal Medicine, PO Box 37, Arcade, NY 14009. Tel: 716-867-6333 Fax: 716-264-4271 E-mail: [email protected]
268
Western New York, which includes Buffalo, the Niagara Falls area, and the Southern Tier, historically has been among the regions in the United States with the highest rate of heart disease and stroke.1 Key cardiovascular risk factors include abnormal lipid levels, such as elevated low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels.2,3 Statins are widely used to control LDL-C levels and reduce the risk of morbidity and mortality2; however, statin-treated patients may have high fasting TG levels despite LDL-C control.4 Because high TG levels are associated with an increased risk of cardiovascular events, cardiovascular death, and myocardial infarction,3 many statin-treated patients have a residual risk of disease.4 Consequently, patients receiv-
© Postgraduate Medicine, Volume 126, Issue 3, May 2014, ISSN – 0032-5481, e-ISSN – 1941-9260 ResearchSHARE®: www.research-share.com • Permissions: [email protected] • Reprints: [email protected] Warning: No duplication rights exist for this journal. Only JTE Multimedia, LLC holds rights to this publication. Please contact the publisher directly with any queries.
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Lipid Effects of Switching From OM3EE to IPE
ing statin therapy may require add-on therapy to control TG levels. Icosapent ethyl (IPE; Vascepa [formerly AMR101]; Amarin Pharma Inc.) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved by the US Food and Drug Administration (FDA) as an adjunct to diet to reduce TG levels in adult patients with severe ($ 500 mg/dL) hypertriglyceridemia.5 Omega-3 fatty acid ethyl esters (OM3EE; Lovaza; GlaxoSmithKline) is approved by the FDA for this same indication.6 In contrast to IPE, which contains EPA as its sole active ingredient,5 OM3EE contains a combination of EPA and docosahexaenoic acid (DHA).6 Both IPE and OM3EE significantly lower TG levels and levels of other lipid parameters in patients with hypertriglyceridemia; however, unlike IPE, OM3EE may increase levels of LDL-C and therefore, as a precaution, these levels should be monitored periodically in patients receiving OM3EE therapy.5,6 Treatment with OM3EE may therefore have effects on LDL-C levels that confound treatment. The objective of the current analysis was to determine the effects of a switch from OM3EE to IPE on patient lipid profiles, including TG and LDL-C levels.
Methods Patients
A retrospective chart review was conducted of patients who had been receiving OM3EE and were subsequently switched to IPE. Patient records were obtained from multiple medical practices at 4 locations in Western New York (Franklinville, Tonawanda, Lancaster, and Niagara Falls). Randomly selected patients were eligible if they were aged $ 18 years with diagnosis codes of high TG levels or hyperlipidemia and had no recent history of myocardial infarction or cancer.
Treatment
Patients were initiated on OM3EE at a dose of 4 g/d and were subsequently switched from OM3EE to IPE at 4 g/d to potentially achieve better outcomes in LDL-C and TG levels. No dietary omega-3 supplementation was allowed; no changes in prescription lipid-lowering medications (LLM; eg, statins, ezetimibe) were allowed.
Assessments
Lipid assessments at the following time points were included in this analysis: before initiation of LLM, while on LLM plus OM3EE (before the switch to IPE), and then again $ 2 months after the switch from OM3EE to IPE (while still on LLM). Assessed parameters included TG, LDL-C, total
cholesterol (TC), non–high-density lipoprotein cholesterol (non–HDL-C) and HDL-C levels. Blood samples for lipid analyses were collected from patients after an overnight fast and analyzed at Niagara Falls Memorial Medical Center Laboratory (Niagara Falls, NY) or Quest Diagnostics (Niagara Falls, NY), as specified by patient insurance. Lowdensity lipoprotein cholesterol assessments were direct or calculated by the clinical laboratory; non–HDL-C level was calculated as TC minus HDL-C.7 Percent change in lipid parameters from levels while on OM3EE to those $ 2 months while on IPE were calculated. Individual patient values while on OM3EE and $ 2 months while on IPE were plotted for visualization of changes in specific lipid parameters among patients.
Results
A total of 15 patients with high TG levels or hyperlipidemia were identified. Treatment with OM3EE was initiated between October 2011 and August 2013. The patients consisted of 11 men and 4 women ranging in age from 45 to 79 years. One patient discontinued treatment and was not included in the analysis of lipid effects. Lipid-lowering medication for the other 14 patients included statins in 10 patients (lovastatin, fluvastatin, atorvastatin, or rosuvastatin) and ezetimibe in 4 (Table 1). Patients were switched from OM3EE to IPE between February and November 2013. In addition to high TG levels or hyperlipidemia, 8 patients also had hypertension, 3 of whom had type 2 diabetes mellitus (Table 1). Individual patient lipid values and changes are shown in Table 1. The amount of time that elapsed between the OM3EE-to-IPE switch and the measurement of lipid parameters during IPE treatment ranged from 2 to 8 months. Lipid levels for patients while on LLM plus OM3EE but before the switch to IPE ranged from 62 to 291 mg/dL for TG, 69 to 211 mg/dL for LDL-C, 155 to 306 mg/dL for TC, 108 to 278 mg/dL for non–HDL-C, and 28 to 71 mg/dL for HDL-C (Table 1). Of the 14 patients with lipid values, 13 experienced decreases in TC and non–HDL-C levels; 12 experienced decreases in TG and LDL-C levels; and changes in HDL-C levels were varied, with no change in 1 patient, decreases in 9 patients, and increases in 4 patients (Table 1). Individual changes from baseline to $ 2 months after switching to IPE are shown in Figure 1. One 45-year-old male patient had an adverse event of gastrointestinal upset after switching to IPE. This patient discontinued treatment after 1 week and did not switch back to OM3EE. The symptom resolved after discontinuation of IPE.
© Postgraduate Medicine, Volume 126, Issue 3, May 2014, ISSN – 0032-5481, e-ISSN – 1941-9260 269 ResearchSHARE®: www.research-share.com • Permissions: [email protected] • Reprints: [email protected] Warning: No duplication rights exist for this journal. Only JTE Multimedia, LLC holds rights to this publication. Please contact the publisher directly with any queries.
270 220 246 212 -13.82 166 197 170 -13.71
232 158 143 -9.49
202 124 109 -12.10 54 49 42 -14.29
138 165 139 -15.76
104 69 63 -8.70
30 34 34 0.00
443 162 156 -3.70
545 270 214 -20.74
52 46 43 -6.52
195 167 144 -13.77
247 213 187 -12.21
138 133 116 -12.78
385 168 160 -4.76
6
65 M Ezetimibe, 10 mg QD HTN
3
34 31 28 -9.68
176 200 210 5.00
210 231 238 3.03
145 142 115 -19.01
453 291 287 -1.37
3
54 M Lovastatin, 40 mg QD
4
53 49 57 16.33
162 170 158 -7.06
215 219 215 -1.83
138 155 149 -3.87
321 98 110 12.24
2
62 M Atorvastatin, 10 mg QD
5
55 57 56 -1.75
140 130 109 -16.15
195 187 165 -11.76
118 112 92 -17.86
111 92 84 -8.70
6
76 M Ezetimibe, 10 mg QD
6
48 47 42 -10.64
207 108 78 -27.78
255 155 120 -22.58
183 90 73 -18.89
484 113 59 -47.79
5
61 M Atorvastatin, 20 mg QD
7
35 44 46 4.55
205 159 134 -15.72
240 203 180 -11.33
141 127 107 -15.75
364 161 134 -16.77
8
57 M Atorvastatin, 20 mg QD HTN
8
31 28 31 10.71
296 278 237 -14.75
327 306 268 -12.42
217 211 195 -7.58
395 169 160 -5.33
49 M Rosuvastatin, 20 mg QD HTN T2DM 3
9
74 64 55 -14.06
159 196 183 -6.63
233 260 238 -8.46
137 146 143 -2.05
308 248 208 -16.13
2
54 F Ezetimibe, 10 mg QD HTN
10
50 71 56 -21.13
212 149 128 -14.09
262 220 184 -16.36
183 130 112 -13.85
213 62 81 30.65
74 F Rosuvastatin, 10 mg QD HTN T2DM 6
11
53 57 55 -3.51
200 198 195 -1.52
253 255 250 -1.96
152 123 172 39.84
342 125 117 -6.40
79 F Ezetimibe, 10 mg QD HTN T2DM 7
12
38 42 48 14.29
241 140 124 -11.43
279 182 172 -5.49
152 92 97 5.43
393 240 166 -30.83
6
70 F Rosuvastatin, 20 mg QD HTN
13
29 46 45 -2.17
217 139 132 -5.04
246 185 177 -4.32
137 101 100 -0.99
404 190 162 -14.74
4
65 M Lovastatin, 40 mg QD
14
a All patients continued to receive LLM; % changes represent change in lipid levels between OM3EE and IPE treatment. Abbreviations: F, female; HDL-C, high-density lipoprotein cholesterol; HTN, hypertension; IPE, icosapent ethyl; LDL-C, low-density lipoprotein cholesterol; LLM, lipid-lowering medication; M, male; OM3EE, omega-3 fatty acid ethyl esters; QD, once daily; T2DM, type 2 diabetes mellitus; TC, total cholesterol; TG, triglycerides.
Before any LLM On OM3EE On IPE % Changea
2
54 M Fluvastatin, 40 mg QD
2
3
57 M Lovastatin, 40 mg QD HTN
Age, y Gender Concomitant LLM
Additional relevant conditions Approximate time from switch to measurement, months TG (mg/dL) Before any LLM On OM3EE On IPE % Changea LDL-C (mg/dL) Before any LLM On OM3EE On IPE % Changea TC (mg/dL) Before any LLM On OM3EE On IPE % Changea Non–HDL-C (mg/dL) Before any LLM On OM3EE On IPE % Changea HDL-C (mg/dL)
1
Patient #
Table 1. Lipid Levels in Patients With Hyperlipidemia Switched From OM3EE to IPE
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Richard S. Castaldo
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Lipid Effects of Switching From OM3EE to IPE
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Figure 1. Individual changes in lipid parameters before and after switch from OM3EE to IPE in patients with hyperlipidemia. A) TG; B) LDL-C; C) total cholesterol; D) non–HDL-C; E) HDL-C.
Abbreviations: HDL-C, high-density lipoprotein cholesterol; IPE, icosapent ethyl; LDL-C, low-density lipoprotein cholesterol; OM3EE, omega-3 fatty acid ethyl esters; TG, triglycerides.
Discussion
In this retrospective real-world analysis, the medical records of patients with hyperlipidemia were analyzed to assess potential lipid effects of switching from OM3EE to IPE. The results demonstrated that after switching from OM3EE to IPE, most patients experienced decreases in TG, LDL-C, TC, and non–HDL-C levels. Although the lipid effects of switching from OM3EE to IPE have not been investigated in a clinical trial, the lipid-lowering effects of OM3EE and IPE in statin-treated patients have been described separately in the Combination of Prescription Omega-3 with Simvastatin (COMBOS)8 and ANCHOR9 studies, respectively. In the 8-week COMBOS study, OM3EE was assessed in statin-treated patients with persistent hypertriglyceridemia (TG levels $ 200 and , 500 mg/dL). Compared with placebo, an addition of OM3EE to simvastatin decreased median TG levels by 23.2% (P , 0.0001), decreased non-HDL levels by 6.8% (P , 0.0001), decreased TC levels by 3.1% (P , 0.05), increased LDL-C levels by 3.5% (P = 0.05) and increased HDL-C levels by 4.6% (P , 0.05).6 The ANCHOR study was a phase 3, multicenter, placebo-controlled, randomized, double-blind, 12-week study of high-risk statin-treated patients
with residually high TG levels ($ 200 and , 500 mg/dL) despite statin control of LDL-C levels ($ 40 mg/dL and , 115 mg/dL). In ANCHOR, IPE at 4 g/d significantly decreased median TG levels by 21.5%, non–HDL-C levels by 13.6%, TC levels by 12% (all P , 0.0001), LDL-C levels by 6.2% (P = 0.0067), and HDL-C levels by 4.5% (P = 0.0013) compared with placebo. Thus, the reductions in TG and LDL-C levels and in other lipid parameters after the switch from OM3EE to IPE in the present study are consistent with those of IPE in the ANCHOR study. A recent report described the lipid effects of 2 patients switching from an EPA plus DHA formulation to IPE; 1 patient treated with statin was switched from an EPA-plus-DHA supplement to IPE, and another patient not receiving statins was switched from OM3EE to IPE.10 In both cases, reductions were observed in levels of TG, LDL-C, TC, and non–HDL-C, with small increases in HDL-C levels. The findings in the present report are consistent with these 2 cases. Although it was known that IPE might lower LDL-C in statin-treated patients, whether LDL-C level would change after a switch from OM3EE to IPE treatment was not known. In the present report, LDL-C levels decreased in 12 patients,
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Richard S. Castaldo
although the decrease was only 1% in 1 case. This may be related to the potential differential effects of EPA and DHA on LDL-C levels. In a meta-analysis of 21 randomized controlled trials in patients with high TG levels, DHA was found to increase LDL-C levels and EPA was found to nonsignificantly reduce LDL-C levels.11 Although small increases in HDL-C levels were observed in the 2 previously reported cases of switching from EPA-plus-DHA formulations to IPE,10 HDL-C effects were varied in the present analysis. These variations in HDL-C findings may be caused by individual patient differences, differences in laboratory measurement methods, or other factors, but it may also be worth noting that the changes in HDL-C levels were small relative to the changes in other lipid parameters, such as TG and TC levels. Furthermore, the clinical importance of small or even large changes in HDL-C levels may be questionable, because recently reported cardiovascular outcomes trials12–14 have challenged the hypothesis that increasing HDL-C levels protects against cardiovascular disease. Icosapent ethyl was found to be well tolerated, with a safety profile similar to that of placebo in the Multicenter, Placebo-Controlled, Randomized, Double-Blind, 12-Week Study with an Open-label Extension (MARINE) and ANCHOR studies.9,15 The adverse event of gastrointestinal upset in the present study was consistent with the MARINE and ANCHOR studies. In the ANCHOR study, 11.6% and 17.2% of patients in the groups receiving IPE at 4 g/d and placebo, respectively, experienced gastrointestinal disorders, including diarrhea and nausea; fewer patients in the group receiving IPE at 4 g/d experienced diarrhea, nausea, and eructation than in the groups receiving either IPE at 2 g/d or placebo in the MARINE trial. The present report has several limitations. It was a retrospective analysis with a small number of patients with different underlying medical conditions and different LLM, the lipid measurement methods and time points varied among patients, and the same clinical laboratory was not used for all patient samples. Additional retrospective or prospective studies are needed to fully characterize the lipid effects of switching from omega-3 fatty acid formulations containing EPA plus DHA to those containing purified EPA. Regarding whether the lipid-lowering effects of pure EPA treatment confer cardiovascular protection, the long-term use of highly purified EPA with statin therapy has been shown to be effective in the prevention of major coronary events in a large population of . 18 000 patients in the Japan EPA Lipid Intervention Study (JELIS).16 The Reduction of Cardiovascular Events With EPA–Intervention Trial (REDUCE-IT; 272
ClinicalTrials.gov identifier: NCT01492361) is investigating the effects of IPE on cardiovascular outcomes in high-risk patients with hypertriglyceridemia treated with statins. Although the 2013 American College of Cardiology/ American Heart Association cholesterol guidelines do not emphasize or recommend target LDL-C levels or provide treatment targets for high TG levels, they do emphasize that higher-risk patient populations with LDL-C levels $ 190 mg/dL, and patients aged 40 to 75 years with LDL-C levels of 70 to 189 mg/dL and diabetes mellitus and/or 10-year risk of $ 7.5%, should be treated more aggressively.17 These new guidelines may ignore the potential benefits of a lower specific LDL-C level, but many physicians in the primary care arena will likely continue to monitor their patients’ LDL-C levels in light of the fact that other current guidelines, such as those from the International Atherosclerosis Society, European Atherosclerosis Society, American Diabetes Association, and American Association of Clinical Endocrinologists, continue to provide LDL-C targets.18–21 The potential beneficial effects on LDL-C levels described in the cases presented herein are worth noting in light of an aggressive treatment approach.
Conclusion
In summary, this real-world retrospective analysis of patients with hyperlipidemia demonstrated that switching patients from OM3EE to IPE resulted in reductions in TG, LDL-C, TC, and non–HDL-C levels, with mixed results for HDL-C levels. These results are consistent with the previously reported ANCHOR trial and 2 recently reported cases of patients switching from EPA-plus-DHA formulations to IPE. The reductions in LDL-C observed in patients in this analysis may suggest a potential beneficial effect of IPE.
Acknowledgments
Editorial and writing assistance was provided by Peloton Advantage, Parsippany, NJ and funded by Amarin Pharma Inc., Bedminster, NJ.
Conflict of Interest Statement
Richard S. Castaldo, MD, is a remunerated consultant for Amarin Pharma Inc.
References 1. Research Center for Stroke and Heart Disease. Jacobs Neurological Institute. Statistics and Facts: Stroke and Heart Disease Facts and Statistics for Western New York. http://www.strokeheart.org/stats.html. Accessed March 31, 2014.
© Postgraduate Medicine, Volume 126, Issue 3, May 2014, ISSN – 0032-5481, e-ISSN – 1941-9260 ResearchSHARE®: www.research-share.com • Permissions: [email protected] • Reprints: [email protected] Warning: No duplication rights exist for this journal. Only JTE Multimedia, LLC holds rights to this publication. Please contact the publisher directly with any queries.
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Lipid Effects of Switching From OM3EE to IPE 2. Baigent C, Keech A, Kearney PM, et al; Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–1278. 3. Murad MH, Hazem A, Coto-Yglesias F, et al. The association of hypertriglyceridemia with cardiovascular events and pancreatitis: a systematic review and meta-analysis. BMC Endocr Disord. 2012;12:2. 4. Miller M, Stone NJ, Ballantyne C, et al; American Heart Association Clinical Lipidology, Thrombosis, and Prevention Committee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123:2292–2333. 5. Vascepa [package insert]. Bedminster, NJ: Amarin Pharma Inc.; 2013. 6. Lovaza [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2013. 7. Havel RJ, Rapaport E. Management of primary hyperlipidemia. N Engl J Med. 1995;332:1491–1498. 8. Davidson MH, Stein EA, Bays HE, et al. COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:1354–1367. 9. 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. 10. Hilleman DE, Malesker MA. Potential benefits of icosapent ethyl on the lipid profile: case studies. Clin Med Insights Cardiol. 2014;8:13–15. 11. Wei MY, Jacobson TA. Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. Curr Atheroscler Rep. 2011;13:474–483. 12. Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–2267. 13. HPS2-THRIVE Collaborative Group. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013;34:1279–1291.
14. Armitage J. HPS2-THRIVE: randomized placebo-controlled trial of ER niacin and laropiprant in 25,673 patients with pre-existing cardiovascular disease. Paper presented at: Annual Scientific Session of the American College of Cardiology; March 9–11, 2013; San Francisco, CA. 15. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. 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). Am J Cardiol. 2011;108:682–690. 16. 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. Lancet. 2007;369:1090–1098. 17. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published online ahead of print November 12, 2013]. Circulation. doi:10.1016/j.jacc.2013.11.002. 18. An International Atherosclerosis Society Position Paper: Global Recommendations for the Management of Dyslipidemia. Full Report. International Atherosclerosis Society. http://www.athero.org/aboutias. asp. Accessed January 10, 2014. 19. European Association for Cardiovascular Prevention and Rehabilitation, Reiner Z, Catapano AL, et al; ESC Committee for Practice Guidelines (CPG) 2008–2010 and 2010–2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32:1769–1818. 20. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(Suppl 1):S14–S80. 21. Jellinger PS, Smith DA, Mehta AE, et al; AACE Task Force for Management of Dyslipidemia and Prevention of Atherosclerosis. American Association of Clinical Endocrinologists’ Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis. Endocr Pract. 2012;18(Suppl 1):1–78.
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A Retrospective Case Series of the Lipid Effects of Switching From Omega-3 Fatty Acid Ethyl Esters to Icosapent Ethyl in Hyperlipidemic Patients Richard S. Castaldo MD To cite this article: Richard S. Castaldo MD (2014) A Retrospective Case Series of the Lipid Effects of Switching From Omega-3 Fatty Acid Ethyl Esters to Icosapent Ethyl in Hyperlipidemic Patients, Postgraduate Medicine, 126:3, 268-273 To link to this article: http://dx.doi.org/10.3810/pgm.2014.05.2775
Published online: 13 Mar 2015.
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C A S E R E P O RT
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A Retrospective Case Series of the Lipid Effects of Switching From Omega-3 Fatty Acid Ethyl Esters to Icosapent Ethyl in Hyperlipidemic Patients
DOI: 10.3810/pgm.2014.05.2775
Richard S. Castaldo, MD Niagara Falls Memorial Medical Center, River Road Primary Care Center, North Tonawanda, NY
Abstract
Background: Western New York is among the regions with the highest rate of heart disease and stroke in the United States. Multifactorial causes include hypertriglyceridemia and dyslipidemia, and additional therapies may be needed to reduce residual risk that remains even after treatment with statins or other lipid-lowering medications. The purpose of this study was to evaluate the effects of a switch from omega-3 fatty acid ethyl esters (OM3EE) to icosapent ethyl (IPE) on lipid profiles in patients with hyperlipidemia. Methods: This was a retrospective chart review of patient records extracted from multiple medical practices throughout Western New York (4 locations). Randomly selected patients (N = 15) were eligible if they were aged $ 18 years with diagnosis codes for high triglyceride (TG) levels or hyperlipidemia and were receiving OM3EE. They were switched from OM3EE to IPE, and lipid parameters were measured after $ 2 months. Results: The records of 15 patients were analyzed and lipid measurements were available for 14 patients; 10 were on statins and 4 were on ezetimibe. At $ 2 months after the switch to IPE, 13 patients experienced decreases in total cholesterol (TC) and non–high-density lipoprotein cholesterol (non–HDL-C) levels; 12 experienced a decrease in TG and low-density lipoprotein cholesterol (LDL-C) levels; and changes in HDL-C levels were varied, with no change in 1 patient, decreases in 9 patients, and increases in 4 patients. Conclusion: The results of this real-world retrospective analysis of 14 patients with hyperlipidemia demonstrated reductions in TG, LDL-C, TC, and non–HDL-C levels, with mixed results in HDL-C levels, after switching from OM3EE to IPE. Keywords: eicosapentaenoic acid; hypertriglyceridemia; hyperlipidemia; omega-3 fatty acids; low-density lipoprotein cholesterol; triglycerides; Lovaza; Vascepa
Introduction
Correspondence: Richard S. Castaldo, MD, Internal Medicine, PO Box 37, Arcade, NY 14009. Tel: 716-867-6333 Fax: 716-264-4271 E-mail: [email protected]
268
Western New York, which includes Buffalo, the Niagara Falls area, and the Southern Tier, historically has been among the regions in the United States with the highest rate of heart disease and stroke.1 Key cardiovascular risk factors include abnormal lipid levels, such as elevated low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels.2,3 Statins are widely used to control LDL-C levels and reduce the risk of morbidity and mortality2; however, statin-treated patients may have high fasting TG levels despite LDL-C control.4 Because high TG levels are associated with an increased risk of cardiovascular events, cardiovascular death, and myocardial infarction,3 many statin-treated patients have a residual risk of disease.4 Consequently, patients receiv-
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Lipid Effects of Switching From OM3EE to IPE
ing statin therapy may require add-on therapy to control TG levels. Icosapent ethyl (IPE; Vascepa [formerly AMR101]; Amarin Pharma Inc.) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved by the US Food and Drug Administration (FDA) as an adjunct to diet to reduce TG levels in adult patients with severe ($ 500 mg/dL) hypertriglyceridemia.5 Omega-3 fatty acid ethyl esters (OM3EE; Lovaza; GlaxoSmithKline) is approved by the FDA for this same indication.6 In contrast to IPE, which contains EPA as its sole active ingredient,5 OM3EE contains a combination of EPA and docosahexaenoic acid (DHA).6 Both IPE and OM3EE significantly lower TG levels and levels of other lipid parameters in patients with hypertriglyceridemia; however, unlike IPE, OM3EE may increase levels of LDL-C and therefore, as a precaution, these levels should be monitored periodically in patients receiving OM3EE therapy.5,6 Treatment with OM3EE may therefore have effects on LDL-C levels that confound treatment. The objective of the current analysis was to determine the effects of a switch from OM3EE to IPE on patient lipid profiles, including TG and LDL-C levels.
Methods Patients
A retrospective chart review was conducted of patients who had been receiving OM3EE and were subsequently switched to IPE. Patient records were obtained from multiple medical practices at 4 locations in Western New York (Franklinville, Tonawanda, Lancaster, and Niagara Falls). Randomly selected patients were eligible if they were aged $ 18 years with diagnosis codes of high TG levels or hyperlipidemia and had no recent history of myocardial infarction or cancer.
Treatment
Patients were initiated on OM3EE at a dose of 4 g/d and were subsequently switched from OM3EE to IPE at 4 g/d to potentially achieve better outcomes in LDL-C and TG levels. No dietary omega-3 supplementation was allowed; no changes in prescription lipid-lowering medications (LLM; eg, statins, ezetimibe) were allowed.
Assessments
Lipid assessments at the following time points were included in this analysis: before initiation of LLM, while on LLM plus OM3EE (before the switch to IPE), and then again $ 2 months after the switch from OM3EE to IPE (while still on LLM). Assessed parameters included TG, LDL-C, total
cholesterol (TC), non–high-density lipoprotein cholesterol (non–HDL-C) and HDL-C levels. Blood samples for lipid analyses were collected from patients after an overnight fast and analyzed at Niagara Falls Memorial Medical Center Laboratory (Niagara Falls, NY) or Quest Diagnostics (Niagara Falls, NY), as specified by patient insurance. Lowdensity lipoprotein cholesterol assessments were direct or calculated by the clinical laboratory; non–HDL-C level was calculated as TC minus HDL-C.7 Percent change in lipid parameters from levels while on OM3EE to those $ 2 months while on IPE were calculated. Individual patient values while on OM3EE and $ 2 months while on IPE were plotted for visualization of changes in specific lipid parameters among patients.
Results
A total of 15 patients with high TG levels or hyperlipidemia were identified. Treatment with OM3EE was initiated between October 2011 and August 2013. The patients consisted of 11 men and 4 women ranging in age from 45 to 79 years. One patient discontinued treatment and was not included in the analysis of lipid effects. Lipid-lowering medication for the other 14 patients included statins in 10 patients (lovastatin, fluvastatin, atorvastatin, or rosuvastatin) and ezetimibe in 4 (Table 1). Patients were switched from OM3EE to IPE between February and November 2013. In addition to high TG levels or hyperlipidemia, 8 patients also had hypertension, 3 of whom had type 2 diabetes mellitus (Table 1). Individual patient lipid values and changes are shown in Table 1. The amount of time that elapsed between the OM3EE-to-IPE switch and the measurement of lipid parameters during IPE treatment ranged from 2 to 8 months. Lipid levels for patients while on LLM plus OM3EE but before the switch to IPE ranged from 62 to 291 mg/dL for TG, 69 to 211 mg/dL for LDL-C, 155 to 306 mg/dL for TC, 108 to 278 mg/dL for non–HDL-C, and 28 to 71 mg/dL for HDL-C (Table 1). Of the 14 patients with lipid values, 13 experienced decreases in TC and non–HDL-C levels; 12 experienced decreases in TG and LDL-C levels; and changes in HDL-C levels were varied, with no change in 1 patient, decreases in 9 patients, and increases in 4 patients (Table 1). Individual changes from baseline to $ 2 months after switching to IPE are shown in Figure 1. One 45-year-old male patient had an adverse event of gastrointestinal upset after switching to IPE. This patient discontinued treatment after 1 week and did not switch back to OM3EE. The symptom resolved after discontinuation of IPE.
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270 220 246 212 -13.82 166 197 170 -13.71
232 158 143 -9.49
202 124 109 -12.10 54 49 42 -14.29
138 165 139 -15.76
104 69 63 -8.70
30 34 34 0.00
443 162 156 -3.70
545 270 214 -20.74
52 46 43 -6.52
195 167 144 -13.77
247 213 187 -12.21
138 133 116 -12.78
385 168 160 -4.76
6
65 M Ezetimibe, 10 mg QD HTN
3
34 31 28 -9.68
176 200 210 5.00
210 231 238 3.03
145 142 115 -19.01
453 291 287 -1.37
3
54 M Lovastatin, 40 mg QD
4
53 49 57 16.33
162 170 158 -7.06
215 219 215 -1.83
138 155 149 -3.87
321 98 110 12.24
2
62 M Atorvastatin, 10 mg QD
5
55 57 56 -1.75
140 130 109 -16.15
195 187 165 -11.76
118 112 92 -17.86
111 92 84 -8.70
6
76 M Ezetimibe, 10 mg QD
6
48 47 42 -10.64
207 108 78 -27.78
255 155 120 -22.58
183 90 73 -18.89
484 113 59 -47.79
5
61 M Atorvastatin, 20 mg QD
7
35 44 46 4.55
205 159 134 -15.72
240 203 180 -11.33
141 127 107 -15.75
364 161 134 -16.77
8
57 M Atorvastatin, 20 mg QD HTN
8
31 28 31 10.71
296 278 237 -14.75
327 306 268 -12.42
217 211 195 -7.58
395 169 160 -5.33
49 M Rosuvastatin, 20 mg QD HTN T2DM 3
9
74 64 55 -14.06
159 196 183 -6.63
233 260 238 -8.46
137 146 143 -2.05
308 248 208 -16.13
2
54 F Ezetimibe, 10 mg QD HTN
10
50 71 56 -21.13
212 149 128 -14.09
262 220 184 -16.36
183 130 112 -13.85
213 62 81 30.65
74 F Rosuvastatin, 10 mg QD HTN T2DM 6
11
53 57 55 -3.51
200 198 195 -1.52
253 255 250 -1.96
152 123 172 39.84
342 125 117 -6.40
79 F Ezetimibe, 10 mg QD HTN T2DM 7
12
38 42 48 14.29
241 140 124 -11.43
279 182 172 -5.49
152 92 97 5.43
393 240 166 -30.83
6
70 F Rosuvastatin, 20 mg QD HTN
13
29 46 45 -2.17
217 139 132 -5.04
246 185 177 -4.32
137 101 100 -0.99
404 190 162 -14.74
4
65 M Lovastatin, 40 mg QD
14
a All patients continued to receive LLM; % changes represent change in lipid levels between OM3EE and IPE treatment. Abbreviations: F, female; HDL-C, high-density lipoprotein cholesterol; HTN, hypertension; IPE, icosapent ethyl; LDL-C, low-density lipoprotein cholesterol; LLM, lipid-lowering medication; M, male; OM3EE, omega-3 fatty acid ethyl esters; QD, once daily; T2DM, type 2 diabetes mellitus; TC, total cholesterol; TG, triglycerides.
Before any LLM On OM3EE On IPE % Changea
2
54 M Fluvastatin, 40 mg QD
2
3
57 M Lovastatin, 40 mg QD HTN
Age, y Gender Concomitant LLM
Additional relevant conditions Approximate time from switch to measurement, months TG (mg/dL) Before any LLM On OM3EE On IPE % Changea LDL-C (mg/dL) Before any LLM On OM3EE On IPE % Changea TC (mg/dL) Before any LLM On OM3EE On IPE % Changea Non–HDL-C (mg/dL) Before any LLM On OM3EE On IPE % Changea HDL-C (mg/dL)
1
Patient #
Table 1. Lipid Levels in Patients With Hyperlipidemia Switched From OM3EE to IPE
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Richard S. Castaldo
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Lipid Effects of Switching From OM3EE to IPE
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Figure 1. Individual changes in lipid parameters before and after switch from OM3EE to IPE in patients with hyperlipidemia. A) TG; B) LDL-C; C) total cholesterol; D) non–HDL-C; E) HDL-C.
Abbreviations: HDL-C, high-density lipoprotein cholesterol; IPE, icosapent ethyl; LDL-C, low-density lipoprotein cholesterol; OM3EE, omega-3 fatty acid ethyl esters; TG, triglycerides.
Discussion
In this retrospective real-world analysis, the medical records of patients with hyperlipidemia were analyzed to assess potential lipid effects of switching from OM3EE to IPE. The results demonstrated that after switching from OM3EE to IPE, most patients experienced decreases in TG, LDL-C, TC, and non–HDL-C levels. Although the lipid effects of switching from OM3EE to IPE have not been investigated in a clinical trial, the lipid-lowering effects of OM3EE and IPE in statin-treated patients have been described separately in the Combination of Prescription Omega-3 with Simvastatin (COMBOS)8 and ANCHOR9 studies, respectively. In the 8-week COMBOS study, OM3EE was assessed in statin-treated patients with persistent hypertriglyceridemia (TG levels $ 200 and , 500 mg/dL). Compared with placebo, an addition of OM3EE to simvastatin decreased median TG levels by 23.2% (P , 0.0001), decreased non-HDL levels by 6.8% (P , 0.0001), decreased TC levels by 3.1% (P , 0.05), increased LDL-C levels by 3.5% (P = 0.05) and increased HDL-C levels by 4.6% (P , 0.05).6 The ANCHOR study was a phase 3, multicenter, placebo-controlled, randomized, double-blind, 12-week study of high-risk statin-treated patients
with residually high TG levels ($ 200 and , 500 mg/dL) despite statin control of LDL-C levels ($ 40 mg/dL and , 115 mg/dL). In ANCHOR, IPE at 4 g/d significantly decreased median TG levels by 21.5%, non–HDL-C levels by 13.6%, TC levels by 12% (all P , 0.0001), LDL-C levels by 6.2% (P = 0.0067), and HDL-C levels by 4.5% (P = 0.0013) compared with placebo. Thus, the reductions in TG and LDL-C levels and in other lipid parameters after the switch from OM3EE to IPE in the present study are consistent with those of IPE in the ANCHOR study. A recent report described the lipid effects of 2 patients switching from an EPA plus DHA formulation to IPE; 1 patient treated with statin was switched from an EPA-plus-DHA supplement to IPE, and another patient not receiving statins was switched from OM3EE to IPE.10 In both cases, reductions were observed in levels of TG, LDL-C, TC, and non–HDL-C, with small increases in HDL-C levels. The findings in the present report are consistent with these 2 cases. Although it was known that IPE might lower LDL-C in statin-treated patients, whether LDL-C level would change after a switch from OM3EE to IPE treatment was not known. In the present report, LDL-C levels decreased in 12 patients,
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Richard S. Castaldo
although the decrease was only 1% in 1 case. This may be related to the potential differential effects of EPA and DHA on LDL-C levels. In a meta-analysis of 21 randomized controlled trials in patients with high TG levels, DHA was found to increase LDL-C levels and EPA was found to nonsignificantly reduce LDL-C levels.11 Although small increases in HDL-C levels were observed in the 2 previously reported cases of switching from EPA-plus-DHA formulations to IPE,10 HDL-C effects were varied in the present analysis. These variations in HDL-C findings may be caused by individual patient differences, differences in laboratory measurement methods, or other factors, but it may also be worth noting that the changes in HDL-C levels were small relative to the changes in other lipid parameters, such as TG and TC levels. Furthermore, the clinical importance of small or even large changes in HDL-C levels may be questionable, because recently reported cardiovascular outcomes trials12–14 have challenged the hypothesis that increasing HDL-C levels protects against cardiovascular disease. Icosapent ethyl was found to be well tolerated, with a safety profile similar to that of placebo in the Multicenter, Placebo-Controlled, Randomized, Double-Blind, 12-Week Study with an Open-label Extension (MARINE) and ANCHOR studies.9,15 The adverse event of gastrointestinal upset in the present study was consistent with the MARINE and ANCHOR studies. In the ANCHOR study, 11.6% and 17.2% of patients in the groups receiving IPE at 4 g/d and placebo, respectively, experienced gastrointestinal disorders, including diarrhea and nausea; fewer patients in the group receiving IPE at 4 g/d experienced diarrhea, nausea, and eructation than in the groups receiving either IPE at 2 g/d or placebo in the MARINE trial. The present report has several limitations. It was a retrospective analysis with a small number of patients with different underlying medical conditions and different LLM, the lipid measurement methods and time points varied among patients, and the same clinical laboratory was not used for all patient samples. Additional retrospective or prospective studies are needed to fully characterize the lipid effects of switching from omega-3 fatty acid formulations containing EPA plus DHA to those containing purified EPA. Regarding whether the lipid-lowering effects of pure EPA treatment confer cardiovascular protection, the long-term use of highly purified EPA with statin therapy has been shown to be effective in the prevention of major coronary events in a large population of . 18 000 patients in the Japan EPA Lipid Intervention Study (JELIS).16 The Reduction of Cardiovascular Events With EPA–Intervention Trial (REDUCE-IT; 272
ClinicalTrials.gov identifier: NCT01492361) is investigating the effects of IPE on cardiovascular outcomes in high-risk patients with hypertriglyceridemia treated with statins. Although the 2013 American College of Cardiology/ American Heart Association cholesterol guidelines do not emphasize or recommend target LDL-C levels or provide treatment targets for high TG levels, they do emphasize that higher-risk patient populations with LDL-C levels $ 190 mg/dL, and patients aged 40 to 75 years with LDL-C levels of 70 to 189 mg/dL and diabetes mellitus and/or 10-year risk of $ 7.5%, should be treated more aggressively.17 These new guidelines may ignore the potential benefits of a lower specific LDL-C level, but many physicians in the primary care arena will likely continue to monitor their patients’ LDL-C levels in light of the fact that other current guidelines, such as those from the International Atherosclerosis Society, European Atherosclerosis Society, American Diabetes Association, and American Association of Clinical Endocrinologists, continue to provide LDL-C targets.18–21 The potential beneficial effects on LDL-C levels described in the cases presented herein are worth noting in light of an aggressive treatment approach.
Conclusion
In summary, this real-world retrospective analysis of patients with hyperlipidemia demonstrated that switching patients from OM3EE to IPE resulted in reductions in TG, LDL-C, TC, and non–HDL-C levels, with mixed results for HDL-C levels. These results are consistent with the previously reported ANCHOR trial and 2 recently reported cases of patients switching from EPA-plus-DHA formulations to IPE. The reductions in LDL-C observed in patients in this analysis may suggest a potential beneficial effect of IPE.
Acknowledgments
Editorial and writing assistance was provided by Peloton Advantage, Parsippany, NJ and funded by Amarin Pharma Inc., Bedminster, NJ.
Conflict of Interest Statement
Richard S. Castaldo, MD, is a remunerated consultant for Amarin Pharma Inc.
References 1. Research Center for Stroke and Heart Disease. Jacobs Neurological Institute. Statistics and Facts: Stroke and Heart Disease Facts and Statistics for Western New York. http://www.strokeheart.org/stats.html. Accessed March 31, 2014.
© Postgraduate Medicine, Volume 126, Issue 3, May 2014, ISSN – 0032-5481, e-ISSN – 1941-9260 ResearchSHARE®: www.research-share.com • Permissions: [email protected] • Reprints: [email protected] Warning: No duplication rights exist for this journal. Only JTE Multimedia, LLC holds rights to this publication. Please contact the publisher directly with any queries.
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Lipid Effects of Switching From OM3EE to IPE 2. Baigent C, Keech A, Kearney PM, et al; Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–1278. 3. Murad MH, Hazem A, Coto-Yglesias F, et al. The association of hypertriglyceridemia with cardiovascular events and pancreatitis: a systematic review and meta-analysis. BMC Endocr Disord. 2012;12:2. 4. Miller M, Stone NJ, Ballantyne C, et al; American Heart Association Clinical Lipidology, Thrombosis, and Prevention Committee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Nursing; Council on the Kidney in Cardiovascular Disease. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123:2292–2333. 5. Vascepa [package insert]. Bedminster, NJ: Amarin Pharma Inc.; 2013. 6. Lovaza [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2013. 7. Havel RJ, Rapaport E. Management of primary hyperlipidemia. N Engl J Med. 1995;332:1491–1498. 8. Davidson MH, Stein EA, Bays HE, et al. COMBination of prescription Omega-3 with Simvastatin (COMBOS) Investigators. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29:1354–1367. 9. 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. 10. Hilleman DE, Malesker MA. Potential benefits of icosapent ethyl on the lipid profile: case studies. Clin Med Insights Cardiol. 2014;8:13–15. 11. Wei MY, Jacobson TA. Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. Curr Atheroscler Rep. 2011;13:474–483. 12. Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–2267. 13. HPS2-THRIVE Collaborative Group. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013;34:1279–1291.
14. Armitage J. HPS2-THRIVE: randomized placebo-controlled trial of ER niacin and laropiprant in 25,673 patients with pre-existing cardiovascular disease. Paper presented at: Annual Scientific Session of the American College of Cardiology; March 9–11, 2013; San Francisco, CA. 15. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN. 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). Am J Cardiol. 2011;108:682–690. 16. 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. Lancet. 2007;369:1090–1098. 17. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines [published online ahead of print November 12, 2013]. Circulation. doi:10.1016/j.jacc.2013.11.002. 18. An International Atherosclerosis Society Position Paper: Global Recommendations for the Management of Dyslipidemia. Full Report. International Atherosclerosis Society. http://www.athero.org/aboutias. asp. Accessed January 10, 2014. 19. European Association for Cardiovascular Prevention and Rehabilitation, Reiner Z, Catapano AL, et al; ESC Committee for Practice Guidelines (CPG) 2008–2010 and 2010–2012 Committees. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32:1769–1818. 20. American Diabetes Association. Standards of medical care in diabetes—2014. Diabetes Care. 2014;37(Suppl 1):S14–S80. 21. Jellinger PS, Smith DA, Mehta AE, et al; AACE Task Force for Management of Dyslipidemia and Prevention of Atherosclerosis. American Association of Clinical Endocrinologists’ Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis. Endocr Pract. 2012;18(Suppl 1):1–78.
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