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Hypertriglyceridemia: HELP
Articles by Christie M. Ballantyne
Based on 25 articles published since 2010
(Why 25 articles?)
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Between 2010 and 2020, Christie Ballantyne wrote the following 25 articles about Hypertriglyceridemia.
 
+ Citations + Abstracts
1 Guideline Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. 2011

Miller, Michael / Stone, Neil J / Ballantyne, Christie / Bittner, Vera / Criqui, Michael H / Ginsberg, Henry N / Goldberg, Anne Carol / Howard, William James / Jacobson, Marc S / Kris-Etherton, Penny M / Lennie, Terry A / Levi, Moshe / Mazzone, Theodore / Pennathur, Subramanian / Anonymous3190692 / Anonymous3200692 / Anonymous3210692 / Anonymous3220692. ·University of Maryland, MD, USA. ·Circulation · Pubmed #21502576.

ABSTRACT: -- No abstract --

2 Editorial The editor's roundtable: hypertriglyceridemia. 2013

Friedewald, Vincent E / Ballantyne, Christie M / Bays, Harold E / Jones, Peter H. ·Associate Editor, The American Journal of Cardiology, and Clinical Professor of Medicine, University of Texas Health Science Center, Houston, Texas. Electronic address: vef@argus1.com. ·Am J Cardiol · Pubmed #24079443.

ABSTRACT: -- No abstract --

3 Review Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial. 2018

Nicholls, Stephen J / Lincoff, A Michael / Bash, Dianna / Ballantyne, Christie M / Barter, Philip J / Davidson, Michael H / Kastelein, John J P / Koenig, Wolfgang / McGuire, Darren K / Mozaffarian, Dariush / Pedersen, Terje R / Ridker, Paul M / Ray, Kausik / Karlson, Björn W / Lundström, Torbjörn / Wolski, Kathy / Nissen, Steven E. ·South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia. · Department of Cardiovascular Medicine and Cleveland Clinic Coordinating Center for Clinical Research, Cleveland Clinic, Cleveland, Ohio. · Baylor College of Medicine, Houston, Texas. · University of New South Wales, Sydney, Australia. · University of Chicago, Chicago, Illinois. · Academic Medical Center, Amsterdam, The Netherlands. · Deutsches Herzzentrum München, Technische Universität München, and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany. · Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas. · Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts. · Oslo University Hospital, Oslo, Norway. · Harvard Medical School, Boston, Massachusetts. · Imperial College of London, London, UK. · Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · AstraZeneca Pharmaceuticals, Gothenburg, Sweden. ·Clin Cardiol · Pubmed #30125052.

ABSTRACT: It is uncertain whether omega-3 fatty acids are beneficial in statin-treated patients. Epanova is a mix of omega-3 free fatty acids, not requiring co-ingestion with food, which can lower triglycerides by up to 31%. STRENGTH will examine whether Epanova 4 g daily reduces the rate of cardiovascular events in statin-treated patients with hypertriglyceridemia and low levels of HDL-C at high risk for developing cardiovascular events. STRENGTH is a randomized, double-blind, placebo-controlled trial. Patients had a triglyceride level ≥ 180 to <500 mg/dL and HDL-C < 42 mg/dL (men) or < 47 mg/dL (women) in the presence of either (1) established atherosclerotic cardiovascular disease, (2) diabetes with one additional risk factor, or (3) were other high-risk primary prevention patients, based on age and risk factor assessment. Patients should be treated with a statin, for >4 weeks, and have LDL-C < 100 mg/dL, but were also eligible if LDL-C was ≥100 mg/dL while on maximum tolerated statin therapy. The study will extend from October 30, 2014 to October 30, 2019. 13 086 patients were randomized to Epanova 4 g or placebo daily in addition to standard medical therapy. The primary efficacy outcome is time to first event of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The trial will continue until 1600 patients reach the primary endpoint, with a median duration of therapy of 3 years. STRENGTH will determine whether Epanova 4 g daily will reduce cardiovascular events in statin-treated high-risk patients with hypertriglyceridemia and low HDL-C levels.

4 Clinical Trial Effects of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) on Atherogenic Lipid/Lipoprotein, Apolipoprotein, and Inflammatory Parameters in Patients With Elevated High-Sensitivity C-Reactive Protein (from the ANCHOR Study). 2019

Miller, Michael / Ballantyne, Christie M / Bays, Harold E / Granowitz, Craig / Doyle, Ralph T / Juliano, Rebecca A / Philip, Sephy. ·Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland. Electronic address: mmiller@som.umaryland.edu. · Department of Medicine, Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas. · Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky. · Amarin Pharma Inc, Bedminster, New Jersey. ·Am J Cardiol · Pubmed #31277790.

ABSTRACT: Icosapent ethyl is pure prescription eicosapentaenoic acid approved at 4 g/day as an adjunct to diet to reduce triglycerides (TG) in adults with TG ≥500 mg/dl. Elevated high-sensitivity C-reactive protein (hsCRP) is associated with increased cardiovascular risk. The 12-week ANCHOR study randomized 702 statin-treated patients at increased cardiovascular risk with TG 200 to 499 mg/dl despite low-density lipoprotein cholesterol (LDL-C) control (40 to 99 mg/dl). This post hoc analysis assessed 246 ANCHOR patients with baseline hsCRP ≥ 2.0 mg/L randomized to icosapent ethyl 4 g/day (n = 126; approved dose) or placebo (n = 120). Without increasing LDL-C, icosapent ethyl significantly reduced median TG (-20%; p < 0.0001), non-high-density lipoprotein cholesterol (-12.3%; p < 0.0001), total cholesterol (-11.1%; p < 0.0001), high-density lipoprotein cholesterol (-5.2%; p = 0.0042), very LDL-C (-21.0%; p < 0.0001), very low-density lipoprotein TG (-22.9%; p < 0.0001), remnant lipoprotein cholesterol (-23.0%; p = 0.0125), apolipoprotein B (-7.4%; p = 0.0021), apolipoprotein C-III (-16%; p < 0.0001), oxidized LDL (-13.7%; p = 0.0020), lipoprotein-associated phospholipase A

5 Clinical Trial Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. 2019

Bhatt, Deepak L / Steg, P Gabriel / Miller, Michael / Brinton, Eliot A / Jacobson, Terry A / Ketchum, Steven B / Doyle, Ralph T / Juliano, Rebecca A / Jiao, Lixia / Granowitz, Craig / Tardif, Jean-Claude / Ballantyne, Christie M / Anonymous2730968. ·From Brigham and Women's Hospital Heart and Vascular Center and Harvard Medical School, Boston (D.L.B.) · FACT (French Alliance for Cardiovascular Trials), Département Hospitalo-Universitaire FIRE (Fibrose, Inflammation, and Remodeling), Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, Université Paris-Diderot, INSERM Unité 1148, Paris (P.G.S.) · National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London (P.G.S.) · the Department of Medicine, University of Maryland School of Medicine, Baltimore (M.M.) · the Utah Lipid Center, Salt Lake City (E.A.B.) · the Office of Health Promotion and Disease Prevention, Department of Medicine, Emory University School of Medicine, Atlanta (T.A.J.) · Amarin Pharma, Bedminster, NJ (S.B.K., R.T.D.J., R.A.J., L.J., C.G.) · Montreal Heart Institute, Université de Montréal, Montreal (J.-C.T.) · and the Department of Medicine, Baylor College of Medicine, and the Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston (C.M.B.). ·N Engl J Med · Pubmed #30415628.

ABSTRACT: BACKGROUND: Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, a highly purified eicosapentaenoic acid ethyl ester, lowers triglyceride levels, but data are needed to determine its effects on ischemic events. METHODS: We performed a multicenter, randomized, double-blind, placebo-controlled trial involving patients with established cardiovascular disease or with diabetes and other risk factors, who had been receiving statin therapy and who had a fasting triglyceride level of 135 to 499 mg per deciliter (1.52 to 5.63 mmol per liter) and a low-density lipoprotein cholesterol level of 41 to 100 mg per deciliter (1.06 to 2.59 mmol per liter). The patients were randomly assigned to receive 2 g of icosapent ethyl twice daily (total daily dose, 4 g) or placebo. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. RESULTS: A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.68 to 0.83; P<0.001); the corresponding rates of the key secondary end point were 11.2% and 14.8% (hazard ratio, 0.74; 95% CI, 0.65 to 0.83; P<0.001). The rates of additional ischemic end points, as assessed according to a prespecified hierarchical schema, were significantly lower in the icosapent ethyl group than in the placebo group, including the rate of cardiovascular death (4.3% vs. 5.2%; hazard ratio, 0.80; 95% CI, 0.66 to 0.98; P=0.03). A larger percentage of patients in the icosapent ethyl group than in the placebo group were hospitalized for atrial fibrillation or flutter (3.1% vs. 2.1%, P=0.004). Serious bleeding events occurred in 2.7% of the patients in the icosapent ethyl group and in 2.1% in the placebo group (P=0.06). CONCLUSIONS: Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo. (Funded by Amarin Pharma; REDUCE-IT ClinicalTrials.gov number, NCT01492361 .).

6 Clinical Trial Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on remnant-like particle cholesterol from the MARINE and ANCHOR studies. 2016

Ballantyne, Christie M / Bays, Harold E / Philip, Sephy / Doyle, Ralph T / Braeckman, Rene A / Stirtan, William G / Soni, Paresh N / Juliano, Rebecca A. ·Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, 6565 Fannin St. MSA 601, Houston, TX 77030, USA. Electronic address: cmb@bcm.tmc.edu. · Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA. · Amarin Pharma Inc., Bedminster, NJ, USA. ·Atherosclerosis · Pubmed #27596132.

ABSTRACT: BACKGROUND AND AIMS: Remnant-like particle cholesterol (RLP-C) is atherogenic and may increase atherosclerotic cardiovascular disease risk. Icosapent ethyl is a high-purity prescription eicosapentaenoic acid ethyl ester (approved as an adjunct to diet to reduce triglyceride [TG] levels in adult patients with TGs ≥500 mg/dL [≥5.65 mmol/L] at 4 g/day). In the MARINE and ANCHOR studies, icosapent ethyl reduced TG and other atherogenic lipid parameter levels without increasing low-density lipoprotein cholesterol (LDL-C) levels. This exploratory analysis evaluated the effects of icosapent ethyl on calculated and directly measured RLP-C. METHODS: MARINE (TGs ≥500 and ≤2000 mg/dL [≥5.65 mmol/L and ≤22.6 mmol/L]) and ANCHOR (TGs ≥200 and <500 mg/dL [≥2.26 and <5.65 mmol/L] despite statin-controlled LDL-C) were phase 3, 12-week, double-blind studies that randomized adult patients to icosapent ethyl 4 g/day, 2 g/day, or placebo. This analysis assessed median percent change from baseline to study end in directly measured (immunoseparation assay) RLP-C levels (MARINE, n = 218; ANCHOR, n = 252) and calculated RLP-C levels in the full populations. RESULTS: Icosapent ethyl 4 g/day significantly reduced directly measured RLP-C levels -29.8% (p = 0.004) in MARINE and -25.8% (p = 0.0001) in ANCHOR versus placebo, and also reduced directly measured RLP-C levels to a greater extent in subgroups with higher versus lower baseline TG levels, in patients receiving statins versus no statins (MARINE), and in patients receiving medium/higher-intensity versus lower-intensity statins (ANCHOR). Strong correlations were found between calculated and directly measured RLP-C for baseline, end-of-treatment, and percent change values in ANCHOR and MARINE (0.73-0.92; p < 0.0001 for all). CONCLUSIONS: Icosapent ethyl 4 g/day significantly reduced calculated and directly measured RLP-C levels versus placebo in patients with elevated TG levels from the MARINE and ANCHOR studies.

7 Clinical Trial Effects of icosapent ethyl on lipoprotein particle concentration and size in statin-treated patients with persistent high triglycerides (the ANCHOR Study). 2015

Ballantyne, Christie M / Braeckman, Rene A / Bays, Harold E / Kastelein, John J / Otvos, James D / Stirtan, William G / Doyle, Ralph T / Soni, Paresh N / Juliano, Rebecca A. ·Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. Electronic address: cmb@bcm.tmc.edu. · Amarin Pharma Inc., Bedminster, NJ, USA. · Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA. · Academic Medical Center, Amsterdam, The Netherlands. · LipoScience, Raleigh, NC, USA. ·J Clin Lipidol · Pubmed #26073397.

ABSTRACT: BACKGROUND: Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved at a dose of 4 g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe hypertriglyceridemia (TG ≥ 500 mg/dL). OBJECTIVE: In this prespecified exploratory analysis from the ANCHOR study of patients at high cardiovascular risk with TG ≥ 200 and <500 mg/dL despite statin control of low-density lipoprotein cholesterol, we assessed the effects of IPE on lipoprotein particle concentration and size and examined correlations of atherogenic particles with apolipoprotein B (ApoB). METHODS: Nuclear magnetic resonance spectroscopy was used to measure lipoprotein particle concentration and size. RESULTS: Compared with placebo (n = 211), IPE 4 g/day (n = 216) significantly reduced concentrations of: total (12.2%, P = .0002), large (46.4%, P < .0001), and medium (12.1%, P = .0068) very-low-density lipoprotein (VLDL) particles; total (7.7%, P = .0017) and small (13.5%, P < .0001) LDL particles; and total (7.4%, P < .0001) and large (31.0%, P < .0001) high-density lipoprotein particles. Atherogenic lipoprotein particles (total VLDL and total LDL) correlated with ApoB at baseline (R(2) = 0.57) and week 12 (R(2) = 0.65) as did total LDL particle concentration at baseline (R(2) = 0.53) and week 12 (R(2) = 0.59). Compared with placebo, IPE 4 g/day significantly reduced VLDL (7.7%, P < .0001) and high-density lipoprotein (1.2%, P = .0014) particle sizes with a modest but significant increase in LDL particle size (0.5%, P = .0031). CONCLUSIONS: Compared with placebo, treatment with IPE 4 g/day for 12 weeks reduced key atherogenic lipoprotein particle concentrations. At both baseline and end of study, atherogenic lipoprotein concentrations correlated with ApoB.

8 Clinical Trial Icosapent ethyl, a pure ethyl ester of eicosapentaenoic acid: effects on circulating markers of inflammation from the MARINE and ANCHOR studies. 2013

Bays, Harold E / Ballantyne, Christie M / Braeckman, Rene A / Stirtan, William G / Soni, Paresh N. ·Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA. HBaysMD@aol.com ·Am J Cardiovasc Drugs · Pubmed #23325450.

ABSTRACT: BACKGROUND: Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved by the US Food and Drug Administration as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. In addition to TG-lowering effects, IPE also reduces non-high-density lipoprotein cholesterol and apolipoprotein B levels without significantly increasing low-density lipoprotein cholesterol (LDL-C) in patients with very high TG levels ≥500 mg/dL (MARINE study) and in patients with well-controlled LDL-C and residually high TG levels 200-500 mg/dL (ANCHOR study). This analysis examined the effect of IPE on inflammatory markers in patients from MARINE and ANCHOR. METHODS: MARINE (N = 229) and ANCHOR (N = 702) were Phase III, double-blind studies that randomized hypertriglyceridemic patients to IPE 4 g/day, 2 g/day, or placebo. This analysis assessed the median placebo-adjusted percentage change from baseline in markers representing various stages of atherosclerotic inflammation such as intercellular adhesion molecule-1 (ICAM-1), oxidized low-density lipoprotein (Ox-LDL), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP). RESULTS: Compared to placebo, IPE 4 g/day significantly decreased Ox-LDL (13 %, p < 0.0001, ANCHOR), Lp-PLA(2) (14 %, p < 0.001, MARINE; 19 %, p < 0.0001, ANCHOR), and hsCRP levels (36 %, p < 0.01, MARINE; 22 %, p < 0.001, ANCHOR), but did not significantly change ICAM-1 and IL-6 levels. In the MARINE study, IPE 2 g/day did not significantly change ICAM-1, Ox-LDL, Lp-PLA(2), IL-6, or hsCRP levels. Also, compared to placebo in the ANCHOR study, IPE 2 g/day significantly decreased Lp-PLA(2) levels (8 %, p < 0.0001), but did not significantly change levels of other assessed inflammatory markers. CONCLUSION: Compared to placebo, in hypertriglyceridemic patients, IPE 4 g/day significantly decreased Ox-LDL, Lp-PLA(2), and hsCRP levels.

9 Clinical Trial Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study). 2012

Bays, Harold E / Braeckman, Rene A / Ballantyne, Christie M / Kastelein, John J / Otvos, James D / Stirtan, William G / Soni, Paresh N. ·Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, USA. hbaysmd@aol.com ·J Clin Lipidol · Pubmed #23312052.

ABSTRACT: BACKGROUND: Icosapent ethyl (IPE; formerly AMR101) is a high-purity prescription form of eicosapentaenoic acid ethyl ester. In the MARINE study we evaluated the efficacy and safety of IPE in patients with very high triglycerides (TG; ≥500 mg/dL) and previously demonstrated significant reductions in TG levels with no significant increases in low-density lipoprotein (LDL) cholesterol levels. OBJECTIVES: In this follow-up, exploratory analysis, we report the effects of IPE on lipoprotein particle concentration and size. METHODS: MARINE was a phase 3, multicenter, placebo-controlled, randomized, double-blind, 12-week study. Hypertriglyceridemic patients (N = 229) were randomized to three treatment groups: IPE 4 g/day, IPE 2 g/day, or placebo. Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy. RESULTS: Compared with placebo, IPE 4 g/day significantly reduced median concentrations of large very-low-density lipoprotein (VLDL; -27.9%; P = .0211), total LDL (-16.3%; P = .0006), small LDL (-25.6%; P < .0001), and total high-density lipoprotein (HDL; -7.4%; P = .0063) particles and reduced VLDL particle size (-8.6%; P = .0017). In this patient population with TG ≥500 mg/dL, IPE did not significantly change the overall sizes of LDL or HDL particles. CONCLUSION: IPE 4 g/day significantly reduced large VLDL, total LDL, small LDL, and total HDL particle concentrations and VLDL particle size in patients with TG ≥500 mg/dL. Changes in VLDL particle concentration and size reflect the TG-lowering effects of eicosapentaenoic acid. The reduction in LDL particle concentration with IPE is novel among ω-3 therapies and is consistent with the previously reported reduction in apolipoprotein B and lack of LDL-C increase with IPE in patients with very high TG levels. CLINICAL TRIAL REGISTRATION NUMBER: NCT01047683.

10 Clinical Trial Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). 2012

Ballantyne, Christie M / Bays, Harold E / Kastelein, John J / Stein, Evan / Isaacsohn, Jonathan L / Braeckman, Rene A / Soni, Paresh N. ·Baylor College of Medicine and the Methodist DeBakey Heart and Vascular Center, Houston, Texas, USA. cmb@bcm.tmc.edu ·Am J Cardiol · Pubmed #22819432.

ABSTRACT: AMR101 is an ω-3 fatty acid agent containing ≥96% pure icosapent-ethyl, the ethyl ester of eicosapentaenoic acid. The efficacy and safety of AMR101 were evaluated in this phase 3, multicenter, placebo-controlled, randomized, double-blinded, 12-week clinical trial (ANCHOR) in high-risk statin-treated patients with residually high triglyceride (TG) levels (≥200 and <500 mg/dl) despite low-density lipoprotein (LDL) cholesterol control (≥40 and <100 mg/dl). Patients (n = 702) on a stable diet were randomized to AMR101 4 or 2 g/day or placebo. The primary end point was median percent change in TG levels from baseline versus placebo at 12 weeks. AMR101 4 and 2 g/day significantly decreased TG levels by 21.5% (p <0.0001) and 10.1% (p = 0.0005), respectively, and non-high-density lipoprotein (non-HDL) cholesterol by 13.6% (p <0.0001) and 5.5% (p = 0.0054), respectively. AMR101 4 g/day produced greater TG and non-HDL cholesterol decreases in patients with higher-efficacy statin regimens and greater TG decreases in patients with higher baseline TG levels. AMR101 4 g/day decreased LDL cholesterol by 6.2% (p = 0.0067) and decreased apolipoprotein B (9.3%), total cholesterol (12.0%), very-low-density lipoprotein cholesterol (24.4%), lipoprotein-associated phospholipase A(2) (19.0%), and high-sensitivity C-reactive protein (22.0%) versus placebo (p <0.001 for all comparisons). AMR101 was generally well tolerated, with safety profiles similar to placebo. In conclusion, AMR101 4 g/day significantly decreased median placebo-adjusted TG, non-HDL cholesterol, LDL cholesterol, apolipoprotein B, total cholesterol, very-low-density lipoprotein cholesterol, lipoprotein-associated phospholipase A(2), and high-sensitivity C-reactive protein in statin-treated patients with residual TG elevations.

11 Clinical Trial 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). 2011

Bays, Harold E / Ballantyne, Christie M / Kastelein, John J / Isaacsohn, Jonathan L / Braeckman, Rene A / Soni, Paresh N. ·Louisville Metabolic and Atherosclerosis Research Center, Kentucky, USA. hbaysmd@aol.com ·Am J Cardiol · Pubmed #21683321.

ABSTRACT: AMR101 is an omega-3 fatty acid agent containing ≥96% eicosapentaenoic acid ethyl ester and no docosahexaenoic acid. Previous smaller studies suggested that highly purified eicosapentaenoic acid lowered triglyceride (TG) levels without increasing low-density lipoprotein (LDL) cholesterol levels. TG-lowering therapies such as fibrates, and fish oils containing both eicosapentaenoic acid and docosahexaenoic acid, can substantially increase LDL cholesterol levels when administered to patients with very high TG levels (≥500 mg/dl). The present double-blind study randomized 229 diet-stable patients with fasting TG ≥500 mg/dl and ≤2,000 mg/dl (with or without background statin therapy) to AMR101 4 g/day, AMR101 2 g/day, or placebo. The primary end point was the placebo-corrected median percentage of change in TG from baseline to week 12. The baseline TG level was 680, 657, and 703 mg/dl for AMR101 4 g/day, AMR101 2 g/day, and placebo. AMR101 4 g/day reduced the placebo-corrected TG levels by 33.1% (n = 76, p <0.0001) and AMR101 2 g/day by 19.7% (n = 73, p = 0.0051). For a baseline TG level >750 mg/dl, AMR101 4 g/day reduced the placebo-corrected TG levels by 45.4% (n = 28, p = 0.0001) and AMR101 2 g/day by 32.9% (n = 28, p = 0.0016). AMR101 did not significantly increase the placebo-corrected median LDL cholesterol levels at 4 g/day (-2.3%) or 2 g/day (+5.2%; both p = NS). AMR101 significantly reduced non-high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein-associated phospholipase A(2), very low-density lipoprotein cholesterol, and total cholesterol. AMR101 was generally well tolerated, with a safety profile similar to that of the placebo. In conclusion, the present randomized, double-blind trial of patients with very high TG levels demonstrated that AMR101 significantly reduced the TG levels and improved other lipid parameters without significantly increasing the LDL cholesterol levels.

12 Clinical Trial Long-term efficacy of adding fenofibric acid to moderate-dose statin therapy in patients with persistent elevated triglycerides. 2011

Ballantyne, Christie M / Jones, Peter H / Kelly, Maureen T / Setze, Carolyn M / Lele, Aditya / Thakker, Kamlesh M / Stolzenbach, James C. ·Baylor College of Medicine, Methodist DeBakey Heart and Vascular Center, Houston, TX 77030, USA. cmb@bcm.tmc.edu ·Cardiovasc Drugs Ther · Pubmed #21416219.

ABSTRACT: OBJECTIVE: The objective of this study was to evaluate the long-term efficacy of adding fenofibric acid to moderate-dose statin therapy in patients at goal for low-density lipoprotein cholesterol (LDL-C) but with persistent hypertriglyceridemia. METHODS: This is a post hoc analysis of a subset of patients (N = 92) with mixed dyslipidemia treated with moderate-dose statin (rosuvastatin 20 mg, simvastatin 40 mg, or atorvastatin 40 mg) for 12 weeks in three controlled trials who had achieved LDL-C <100 mg/dL but whose triglycerides remained >200 mg/dL, and had fenofibric acid 135 mg added to the moderate-dose statin in a 52-week open-label extension study. Lipid and apolipoprotein (Apo) values and the proportion of patients meeting individual and combined treatment targets with combination therapy were determined at scheduled visits during the 52-week study and compared with baseline (start of extension study). RESULTS: Addition of fenofibric acid to moderate-dose statin for 52 weeks resulted in significant (P < 0.001) improvements in non-high-density lipoprotein cholesterol (non-HDL-C; -9.0%), ApoB (-9.8%), HDL-C (14.9%), and triglycerides (-37.6%) compared with baseline. At final visit, greater proportions of patients achieved optimal levels of individual parameters as well as combined targets of LDL-C + non-HDL-C (60.0% vs 52.2%), LDL-C + non-HDL-C + ApoB (53.3% vs 37.8%, P = 0.007), and LDL-C + non-HDL-C + ApoB + HDL-C + triglycerides (25.6% vs 0.0%) than at baseline. CONCLUSIONS: The addition of fenofibric acid to moderate-dose statin in patients whose LDL-C was optimal but whose triglycerides remained >200 mg/dL led to additional improvements in non-HDL-C, ApoB, HDL-C, and triglycerides that resulted in greater proportions of patients attaining optimal levels of the individual parameters as well as simultaneously achieving optimal levels of these parameters and LDL-C.

13 Article Icosapent ethyl reduces atherogenic markers in high-risk statin-treated patients with stage 3 chronic kidney disease and high triglycerides. 2019

Vijayaraghavan, Krishnaswami / Szerlip, Harold M / Ballantyne, Christie M / Bays, Harold E / Philip, Sephy / Doyle, Ralph T / Juliano, Rebecca A / Granowitz, Craig. ·a Institute of Congestive Heart Failure, Abrazo Arizona Heart Hospital , Phoenix , AZ , USA. · b Nephrology Division and Nephrology Fellowship Program, Baylor University Medical Center , Dallas , TX , USA. · c Department of Medicine, Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center , Houston , TX , USA. · d Louisville Metabolic and Atherosclerosis Research Center , Louisville , KY , USA. · e Medical Affairs, Amarin Pharma Inc ., Bedminster , NJ , USA. · f Clinical Development, Amarin Pharma Inc ., Bedminster , NJ , USA. ·Postgrad Med · Pubmed #31306043.

ABSTRACT:

14 Article Effects of Icosapent Ethyl on Total Ischemic Events: From REDUCE-IT. 2019

Bhatt, Deepak L / Steg, Ph Gabriel / Miller, Michael / Brinton, Eliot A / Jacobson, Terry A / Ketchum, Steven B / Doyle, Ralph T / Juliano, Rebecca A / Jiao, Lixia / Granowitz, Craig / Tardif, Jean-Claude / Gregson, John / Pocock, Stuart J / Ballantyne, Christie M / Anonymous321188. ·Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, Massachusetts. Electronic address: dlbhattmd@post.harvard.edu. · FACT (French Alliance for Cardiovascular Trials), an F-CRIN network, Département Hospitalo-Universitaire FIRE, AP-HP, Hôpital Bichat, Université Paris-Diderot, INSERM U-1148, Paris, France; National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, London, United Kingdom. · Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland. · Utah Lipid Center, Salt Lake City, Utah. · Office of Health Promotion and Disease Prevention, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia. · Amarin Pharma, Inc. (Amarin), Bedminster, New Jersey. · Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada. · Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, United Kingdom. · Department of Medicine, Baylor College of Medicine; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, Texas. ·J Am Coll Cardiol · Pubmed #30898607.

ABSTRACT: BACKGROUND: In time-to-first-event analyses, icosapent ethyl significantly reduced the risk of ischemic events, including cardiovascular death, among patients with elevated triglycerides receiving statins. These patients are at risk for not only first but also subsequent ischemic events. OBJECTIVES: Pre-specified analyses determined the extent to which icosapent ethyl reduced total ischemic events. METHODS: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) randomized 8,179 statin-treated patients with triglycerides ≥135 and <500 mg/dl (median baseline of 216 mg/dl) and low-density lipoprotein cholesterol >40 and ≤100 mg/dl (median baseline of 75 mg/dl), and a history of atherosclerosis (71% patients) or diabetes (29% patients) to icosapent ethyl 4 g/day or placebo. The main outcomes were total (first and subsequent) primary composite endpoint events (cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) and total key secondary composite endpoint events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). As a pre-specified statistical method, we determined differences in total events using negative binomial regression. We also determined differences in total events using other statistical models, including Andersen-Gill, Wei-Lin-Weissfeld (Li and Lagakos modification), both pre-specified, and a post hoc joint frailty analysis. RESULTS: In 8,179 patients, followed for a median of 4.9 years, 1,606 (55.2%) first primary endpoint events and 1,303 (44.8%) subsequent primary endpoint events occurred (which included 762 second events, and 541 third or more events). Overall, icosapent ethyl reduced total primary endpoint events (61 vs. 89 per 1,000 patient-years for icosapent ethyl versus placebo, respectively; rate ratio: 0.70; 95% confidence interval: 0.62 to 0.78; p < 0.0001). Icosapent ethyl also reduced totals for each component of the primary composite endpoint, as well as the total key secondary endpoint events (32 vs. 44 per 1,000 patient-years for icosapent ethyl versus placebo, respectively; rate ratio: 0.72; 95% confidence interval: 0.63 to 0.82; p < 0.0001). CONCLUSIONS: Among statin-treated patients with elevated triglycerides and cardiovascular disease or diabetes, multiple statistical models demonstrate that icosapent ethyl substantially reduces the burden of first, subsequent, and total ischemic events. (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial [REDUCE-IT]; NCT01492361).

15 Article Icosapent Ethyl Effects on Fatty Acid Profiles in Statin-Treated Patients With High Triglycerides: The Randomized, Placebo-controlled ANCHOR Study. 2019

Ballantyne, Christie M / Manku, Mehar S / Bays, Harold E / Philip, Sephy / Granowitz, Craig / Doyle, Ralph T / Juliano, Rebecca A. ·Department of Medicine, Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. cmb@bcm.tmc.edu. · Amarin Pharma Inc, Bedminster, NJ, USA. · Clinical Research, Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA. · Medical Affairs, Amarin Pharma Inc, Bedminster, NJ, USA. · Research and Development, Amarin Pharma Inc, Bedminster, NJ, USA. ·Cardiol Ther · Pubmed #30788718.

ABSTRACT: INTRODUCTION: Fatty acid content in plasma and red blood cells (RBCs) may provide insight into potential physiologic benefits of omega-3 fatty acids. Icosapent ethyl is a pure prescription form of eicosapentaenoic acid (EPA) ethyl ester approved by the US Food and Drug Administration at a dose of 4 g/day as an adjunct to diet to reduce triglyceride levels in adults with severe (≥ 500 mg/dl) hypertriglyceridemia. METHODS: This was a prespecified exploratory subset analysis of the ANCHOR study, which randomized 702 statin-treated patients at increased cardiovascular risk with triglycerides 200-499 mg/dl and controlled low-density lipoprotein cholesterol (40-99 mg/dl). This analysis examined effects of icosapent ethyl 4 g/day versus placebo on fatty acid levels in plasma and RBCs using a gas chromatograph assay method with flame ionization detector. RESULTS: In plasma, treatment with icosapent ethyl 4 g/day resulted in significant increases versus placebo in the mean concentrations of EPA (+ 635%; P < 0.0001) and its metabolite, docosapentaenoic acid n-3 (+ 143%; P < 0.0001) with no significant change in docosahexaenoic acid. Treatment with icosapent ethyl 4 g/day versus placebo also resulted in significant decreases in the omega-6 fatty acids linoleic acid (- 25%) and arachidonic acid (AA; - 31%), as well as the AA/EPA ratio (- 91%). Icosapent ethyl 4 g/day also decreased the omega-9 fatty acid oleic acid (- 29%) and the saturated fatty acids palmitic acid (- 23%) and stearic acid (- 16%) (all P < 0.0001). Results were similar for RBCs. CONCLUSIONS: Icosapent ethyl 4 g/day significantly increased EPA and produced other potentially beneficial shifts in fatty acids in plasma and RBCs versus placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01047501 FUNDING: Amarin Pharma Inc. Plain language summary available for this article.

16 Article Lipid Effects of Icosapent Ethyl in Women with Diabetes Mellitus and Persistent High Triglycerides on Statin Treatment: ANCHOR Trial Subanalysis. 2018

Brinton, Eliot A / Ballantyne, Christie M / Guyton, John R / Philip, Sephy / Doyle, Ralph T / Juliano, Rebecca A / Mosca, Lori. ·1 Utah Lipid Center , Salt Lake City, Utah. · 2 Department of Medicine, Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center , Houston, Texas. · 3 Department of Endocrinology, Metabolism, and Nutrition, Duke University School of Medicine , Durham, North Carolina. · 4 Medical Affairs, Amarin Pharma, Inc. , Bedminster, New Jersey. · 5 Clinical Development, Amarin Pharma, Inc. , Bedminster, New Jersey. · 6 Department of Medicine, Columbia University Medical Center , New York, New York. ·J Womens Health (Larchmt) · Pubmed #29583081.

ABSTRACT: BACKGROUND: High triglycerides (TG) and diabetes mellitus type 2 (DM2) are stronger predictors of cardiovascular disease (CVD) in women than in men, but few randomized, controlled clinical trials have investigated lipid-lowering interventions in women and none have reported results specifically in women with high TG and DM2. Icosapent ethyl (Vascepa) is pure prescription eicosapentaenoic acid (EPA) ethyl ester approved at 4 g/day as an adjunct to diet to reduce TG ≥500 mg/dL. METHODS: The 12-week ANCHOR trial randomized 702 statin-treated patients (73% with DM; 39% women) at increased CVD risk with TG 200-499 mg/dL despite controlled low-density lipoprotein cholesterol (LDL-C; 40-99 mg/dL) to receive icosapent ethyl 2 g/day, 4 g/day, or placebo. This post hoc analysis included 146 women with DM2 (97% white, mean age 62 years) randomized to icosapent ethyl 4 g/day (n = 74) or placebo (n = 72). RESULTS: Icosapent ethyl significantly reduced TG (-21.5%; p < 0.0001) without increasing LDL-C and lowered other potentially atherogenic lipid/lipoprotein, apolipoprotein, and inflammatory parameters versus placebo. Icosapent ethyl increased EPA levels in plasma (+639%; p < 0.0001; n = 49) and red blood cells (+599%; p < 0.0001; n = 47) versus placebo. Safety and tolerability of icosapent ethyl were generally similar to placebo. CONCLUSION: In women with DM2 at high CVD risk with persistently high TG on statins, icosapent ethyl 4 g/day reduced potentially atherogenic parameters with safety and tolerability comparable to placebo. Potential CVD benefits of icosapent ethyl are being tested in ∼8000 men and women at high CVD risk with high TG on statins in the ongoing Reduction of Cardiovascular Events with Icosapent Ethyl - Intervention Trial (REDUCE-IT) cardiovascular (CV) outcome trial.

17 Article Usefulness of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) in Women to Lower Triglyceride Levels (Results from the MARINE and ANCHOR Trials). 2017

Mosca, Lori / Ballantyne, Christie M / Bays, Harold E / Guyton, John R / Philip, Sephy / Doyle, Ralph T / Juliano, Rebecca A. ·Columbia University Medical Center, New York, New York. Electronic address: ljm10@columbia.edu. · Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas. · Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky. · Duke University School of Medicine, Durham, North Carolina. · Amarin Pharma Inc., Bedminster, New Jersey. ·Am J Cardiol · Pubmed #27939227.

ABSTRACT: There are limited data on the efficacy and safety of triglyceride (TG)-lowering agents in women. We conducted subgroup analyses of the effects of icosapent ethyl (a high-purity prescription form of the ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid) on TG levels (primary efficacy variable) and other atherogenic and inflammatory parameters in a total of 215 women with a broad range of TG levels (200-2000 mg/dl) enrolled in two 12-week placebo-controlled trials: MARINE (n = 18; placebo, n = 18) and ANCHOR (n = 91; placebo, n = 88). Icosapent ethyl 4 g/day significantly reduced TG levels from baseline to week 12 versus placebo in both MARINE (-22.7%; p = 0.0327) and ANCHOR (-21.5%; p <0.0001) without increasing low-density lipoprotein cholesterol levels. Significant improvements were also observed in non-high-density lipoprotein cholesterol levels in MARINE (-15.7%; p = 0.0082) and ANCHOR (-14.2%; p <0.0001) and total cholesterol levels in MARINE (-14.9%; p = 0.0023) and ANCHOR (-12.1%; p <0.0001), along with significant increases of >500% in eicosapentaenoic acid levels in plasma and red blood cells (all p <0.001). Icosapent ethyl was well tolerated, with adverse-event profiles comparable with findings in the overall studies. In conclusion, icosapent ethyl 4 g/day significantly reduced TG levels and other atherogenic parameters in women without increasing low-density lipoprotein cholesterol levels compared with placebo; the clinical implications of these findings are being evaluated in the REDUCtion of Cardiovascular Events With Eicosapentaenoic Acid [EPA]-Intervention Trial (REDUCE-IT) cardiovascular outcomes study.

18 Article Icosapent ethyl: Eicosapentaenoic acid concentration and triglyceride-lowering effects across clinical studies. 2016

Bays, Harold E / Ballantyne, Christie M / Doyle, Ralph T / Juliano, Rebecca A / Philip, Sephy. ·Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA. Electronic address: hbaysmd@aol.com. · Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, 6565 Fannin, M.S. A-601, Houston, TX 77030, USA. Electronic address: cmb@bcm.tmc.edu. · Amarin Pharma Inc., 1430 Route 206, Suite 200, Bedminster, NJ 07921, USA. Electronic address: ralph.doyle@amarincorp.com. · Amarin Pharma Inc., 1430 Route 206, Suite 200, Bedminster, NJ 07921, USA. Electronic address: rebecca.juliano@amarincorp.com. · Amarin Pharma Inc., 1430 Route 206, Suite 200, Bedminster, NJ 07921, USA. Electronic address: sephy.philip@amarincorp.com. ·Prostaglandins Other Lipid Mediat · Pubmed #27418543.

ABSTRACT: Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved at a dose of 4g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500mg/dL) hypertriglyceridemia. This post-hoc exploratory analysis examined the relationship of icosapent ethyl dose with EPA concentrations in plasma and red blood cells (RBCs) across 3 clinical studies-a phase 1 pharmacokinetic study in healthy adult volunteers and 2 pivotal phase 3 studies (MARINE and ANCHOR) in adult patients with hypertriglyceridemia-and examined the relationship between EPA levels and TG-lowering effects in MARINE and ANCHOR. In all 3 studies, icosapent ethyl produced dose-dependent increases in the concentrations of EPA in plasma and RBCs. In both MARINE and ANCHOR, these dose-dependent EPA increases correlated with the degree of TG level lowering (all P<0.01). In patients with high TG levels (≥200mg/dL) and treated with icosapent ethyl 4g/day, the end-of-treatment plasma and RBC EPA concentrations were >170μg/mL and>70μg/mL, respectively. These studies support icosapent ethyl as producing predictable dose-dependent pharmacokinetics/pharmacodynamics, with TG level lowering dependent upon icosapent ethyl dose and EPA concentrations in plasma and RBCs.

19 Article Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on plasma apolipoprotein C-III levels in patients from the MARINE and ANCHOR studies. 2016

Ballantyne, Christie M / Bays, Harold E / Braeckman, Rene A / Philip, Sephy / Stirtan, William G / Doyle, Ralph T / Soni, Paresh N / Juliano, Rebecca A. ·Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. Electronic address: cmb@bcm.tmc.edu. · Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA. · Doylestown, PA, USA. · Amarin Pharma Inc., Bedminster, NJ, USA. · East Lyme, CT, USA. · Mystic, CT, USA. ·J Clin Lipidol · Pubmed #27206952.

ABSTRACT: BACKGROUND: Apolipoprotein C-III (ApoC-III) regulates lipoprotein and triglyceride (TG) metabolism and may have a causal role in cardiovascular disease. In the Multi-Center, Placebo-Controlled, Randomized, Double-Blind, 12-Week Study With an Open-Label Extension (MARINE) and ANCHOR studies, icosapent ethyl, a high-purity prescription eicosapentaenoic acid ethyl ester, reduced TG, and other atherogenic lipid parameters without increasing low-density lipoprotein cholesterol (LDL-C) compared with placebo. OBJECTIVE: To evaluate the effects of icosapent ethyl on plasma ApoC-III levels in patients from 2 phase 3 studies. METHODS: MARINE and ANCHOR were 12-week double-blind studies of icosapent ethyl in adult patients. Patients in MARINE had very high TG levels (≥500 and ≤2000 mg/dL) and patients in ANCHOR had high TG levels (≥200 and <500 mg/dL) despite statin control of LDL-C. This post hoc analysis of MARINE and ANCHOR assessed the median percent change from baseline in plasma ApoC-III levels vs placebo and includes subgroup analyses by statin use/efficacy and median ApoC-III levels. RESULTS: We assessed ApoC-III levels in 148 and 612 patients in the MARINE and ANCHOR studies, respectively. In MARINE, the approved prescription dose of icosapent ethyl (4 g/day) significantly reduced ApoC-III levels by 25.1% (P < .0001) vs placebo. In ANCHOR, icosapent ethyl 4 g/day significantly reduced ApoC-III levels by 19.2% (P < .0001) vs placebo; subanalysis by statin efficacy revealed significant reductions vs placebo in the higher-efficacy and medium-efficacy groups (24.6% and 17.2%, respectively; both P < .0001). CONCLUSION: Icosapent ethyl 4 g/day significantly reduced plasma ApoC-III levels in patients with elevated TGs from the MARINE and ANCHOR studies.

20 Article Effects of fenofibric acid on carotid intima-media thickness in patients with mixed dyslipidemia on atorvastatin therapy: randomized, placebo-controlled study (FIRST). 2014

Davidson, Michael H / Rosenson, Robert S / Maki, Kevin C / Nicholls, Stephen J / Ballantyne, Christie M / Mazzone, Theodore / Carlson, Dawn M / Williams, Laura A / Kelly, Maureen T / Camp, Heidi S / Lele, Aditya / Stolzenbach, James C. ·From the Department of Medicine, University of Chicago, IL (M.H.D.) · Icahn School of Medicine at Mount Sinai, New York, NY (R.S.R.) · Biofortis Clinical Research, Addison, IL (K.C.M.) · Cardiology, University of Adelaide, Adelaide, Australia (S.J.N.) · Consultant Cardiologist, Royal Adelaide Hospital, Adelaide, Australia (S.J.N.) · Section of Cardiology, Section of Atherosclerosis and Vascular Medicine, and Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart Center, Houston, TX (C.M.B.) · the Maria and Alando J. Ballantyne, MD, Atherosclerosis Laboratory, and Lipid Metabolism and Atherosclerosis Clinic, The Methodist Hospital, Houston, TX (C.M.B.) · Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago (T.M.) · and Global Pharmaceutical Research and Development (D.M.C., L.A.W., M.T.K., H.S.C., J.C.S), and Data and Statistical Sciences (A.L.), AbbVie Inc, North Chicago, IL. ·Arterioscler Thromb Vasc Biol · Pubmed #24743431.

ABSTRACT: OBJECTIVE: To assess whether adding a fibrate to statin therapy reduces residual cardiovascular risk associated with elevated triglycerides and low high-density lipoprotein cholesterol, The Evaluation of Choline Fenofibrate (ABT-335) on Carotid Intima-Media Thickness (cIMT) in Subjects with Type IIb Dyslipidemia with Residual Risk in Addition to Atorvastatin Therapy (FIRST) trial evaluated the effects of fenofibric acid (FA) treatment on cIMT in patients with mixed dyslipidemia on atorvastatin. APPROACH AND RESULTS: This multicenter, double-blind, placebo-controlled study was performed in patients with mixed dyslipidemia (fasting triglycerides, ≥150 mg/dL; high-density lipoprotein cholesterol, ≤45 [men] or 55 mg/dL [women]; low-density lipoprotein cholesterol, ≤100 mg/dL once and averaging ≤105 mg/dL) and a history of coronary heart disease or risk equivalent. Patients on background atorvastatin (continued on starting dose or titrated to 40 mg, if needed) were randomized to FA 135 mg or placebo. The primary end point was rate of change from baseline through week 104 of the mean posterior-wall cIMT, measured by ultrasound. In patients with controlled low-density lipoprotein cholesterol while on atorvastatin background therapy, rate of change in posterior-wall cIMT was similar with FA plus atorvastatin (-0.006 mm/y) versus atorvastatin monotherapy (0.000 mm/y; P=0.22). FA plus atorvastatin was favored (P<0.05) in 5 of 24 prespecified subgroups: age ≥60 years, history of coronary artery disease, cIMT >0.795 mm, triglycerides 170 to 235 mg/dL, and statin use at entry. Adverse events were consistent with the known safety profiles of both drugs; however, FA plus atorvastatin was associated with a greater incidence of renal-related adverse events compared with atorvastatin monotherapy (6.5% versus 0.9%). CONCLUSIONS: Compared with atorvastatin monotherapy, FA plus atorvastatin did not further decrease cIMT progression in high-risk patients with mixed dyslipidemia.

21 Article Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency. 2014

Khan, Ilvira M / Dai Perrard, Xiao-Yuan / Perrard, Jerry L / Mansoori, Amir / Smith, C Wayne / Wu, Huaizhu / Ballantyne, Christie M. ·Division of Atherosclerosis and Vascular Medicine, Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA. · Division of Atherosclerosis and Vascular Medicine, Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA. · Section of Leukocyte Biology, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. · Division of Atherosclerosis and Vascular Medicine, Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Section of Leukocyte Biology, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. · Division of Atherosclerosis and Vascular Medicine, Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Section of Leukocyte Biology, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. Electronic address: cmb@bcm.tmc.edu. ·Atherosclerosis · Pubmed #24530773.

ABSTRACT: OBJECTIVES: High-fat diet (HFD) feeding in mice is characterized by accumulation of αβ T cells in adipose tissue. However, the contribution of αβ T cells to obesity-induced inflammation of skeletal muscle, a major organ of glucose uptake, is unknown. This study was undertaken to evaluate the effect of αβ T cells on insulin sensitivity and inflammatory state of skeletal muscle and adipose tissue in obesity. Furthermore, we investigated whether CD4+IFNγ+ (TH1) cells are involved in skeletal muscle and adipose tissue metabolic dysfunction that accompanies obesity. METHODS: Mice lacking αβ T cells (T cell receptor beta chain-deficient [TCRb-/-] mice) were fed HFD for 12 weeks. Obesity-induced skeletal muscle and adipose tissue inflammation was assessed by flow cytometry and quantitative RT-PCR. To investigate the effect of TH1 cells on skeletal muscle and adipose tissue inflammation and metabolic functions, we injected 5×10(5) TH1 cells or PBS weekly over 12 weeks into HFD-fed TCRb-/- mice. We also cultured C2C12 myofibers and 3T3-L1 adipocytes with TH1-conditioned medium. RESULTS: We showed that similar to adipose tissue, skeletal muscle of obese mice have higher αβ T cell content, including TH1 cells. TCRb-/- mice were protected against obesity-induced hyperglycemia and insulin resistance. We also demonstrated suppressed macrophage infiltration and reduced inflammatory cytokine expression in skeletal muscle and adipose tissue of TCRb-/- mice on HFD compared to wild-type obese controls. Adoptive transfer of TH1 cells into HFD-fed TCRb-/- mice resulted in increased skeletal muscle and adipose tissue inflammation and impaired glucose metabolism. TH1 cells directly impaired functions of C2C12 myotubes and 3T3-L1 adipocytes in vitro. CONCLUSIONS: We conclude that reduced adipose tissue and skeletal muscle inflammation in obese TCRb-/- mice is partially attributable to the absence of TH1 cells. Our results suggest an important role of TH1 cells in regulating inflammation and insulin resistance in obesity.

22 Article Icosapent ethyl for the treatment of hypertriglyceridemia. 2013

Ballantyne, Christie M / Braeckman, Rene A / Soni, Paresh N. ·Baylor College of Medicine and Methodist DeBakey Heart and Vascular Center, 6565 Fannin, M.S. A-601, Houston, TX 77030, USA. cmb@bcm.tmc.edu ·Expert Opin Pharmacother · Pubmed #23701295.

ABSTRACT: INTRODUCTION: Icosapent ethyl (IPE; Vascepa) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester recently approved in 2012 to reduce triglyceride (TG) levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia. Elevated TG levels are associated with increased risk for coronary heart disease. Currently available TG-lowering agents (fibrates, niacins, omega-3 fatty acid products containing both EPA and docosahexaenoic acid [DHA]) may be associated with adverse effects such as flushing, hepatotoxicity, myopathy, elevated glucose levels, and/or increases in low-density lipoprotein cholesterol (LDL-C). AREAS COVERED: This review describes IPE chemistry, pharmacokinetics, and clinical studies. In two Phase III randomized, placebo-controlled trials, one in patients with very high TG levels (≥ 500 mg/dL; MARINE) and the other in statin-treated patients at high cardiovascular risk with well-controlled LDL-C and residual high TG levels (≥ 200 to < 500 mg/dL; ANCHOR), IPE lowered levels of TG, non-high-density lipoprotein cholesterol, and other atherogenic lipoproteins without increasing LDL-C levels. EXPERT OPINION: IPE is safe and effective for managing high TG levels, and it offers a new alternative with potential benefits over currently available treatments for dyslipidemia. The ongoing cardiovascular outcomes REDUCE-IT trial will provide valuable information on the efficacy of IPE to prevent cardiovascular events in high-risk patients already taking statins.

23 Article Intensive lifestyle modification reduces Lp-PLA2 in dyslipidemic HIV/HAART patients. 2013

Wooten, Joshua S / Nambi, Preethi / Gillard, Baiba K / Pownall, Henry J / Coraza, Ivonne / Scott, Lynne W / Nambi, Vijay / Ballantyne, Christie M / Balasubramanyam, Ashok. ·Division of Atherosclerosis and Vascular Biology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. ·Med Sci Sports Exerc · Pubmed #23299761.

ABSTRACT: PURPOSE: Patients with dyslipidemia associated with HIV-1 infection and highly active antiretroviral therapy (HAART) have elevated levels of Lp-PLA2 and CCL5/regulated on activation, normal T-cell expressed and secreted (RANTES), which may increase the risk of cardiovascular disease. PURPOSE: This study aimed to determine whether an intensive diet and exercise (D/E) program, independently or combined with fenofibrate or niacin, could reduce Lp-PLA2 or RANTES. METHODS: Patients with hypertriglyceridemic HIV on stable HAART (n = 107) were randomized to one of five interventions: 1) usual care, 2) D/E with placebos, 3) D/E with fenofibrate and placebo, 4) D/E with niacin and placebo, or 5) D/E with fenofibrate and niacin for 24 wk. Lp-PLA2 and RANTES concentrations were measured in fasting plasma samples at baseline and postintervention. General linear models were used to compare Lp-PLA2 and RANTES levels between the five groups postintervention, controlling for baseline levels, age, body mass index, CD4 T-cell count, viral load, duration of infection, and HAART. RESULTS: At baseline, fasting plasma Lp-PLA2 (388.5 ± 127.5 ng·mL) and RANTES (43.8 ± 25.5 ng·mL) levels were elevated when compared with healthy controls. Posttreatment Lp-PLA2 mass was lower in patients who received D/E only (323.0 ± 27.2 ng·mL), D/E plus fenofibrate (327.2 ± 25.9 ng·mL), and D/E plus niacin (311.1 ± 27.8 ng·mL) when compared with patients receiving usual care (402.2 ± 25.3 ng·mL). RANTES concentrations were not significantly affected by any intervention. CONCLUSIONS: Elevated plasma Lp-PLA2 mass can be reduced by an intensive D/E program in patients with HIV/HAART-associated dyslipidemia. RANTES is elevated but is not reduced by lifestyle modification, fenofibrate, or niacin.

24 Article CD11c/CD18 expression is upregulated on blood monocytes during hypertriglyceridemia and enhances adhesion to vascular cell adhesion molecule-1. 2011

Gower, R Michael / Wu, Huaizhu / Foster, Greg A / Devaraj, Sridevi / Jialal, Ishwarlal / Ballantyne, Christie M / Knowlton, Anne A / Simon, Scott I. ·Department of Biomedical Engineering, University of California, Davis, CA 95616, USA. ·Arterioscler Thromb Vasc Biol · Pubmed #21030716.

ABSTRACT: OBJECTIVE: Atherosclerosis is associated with monocyte adhesion to the arterial wall that involves integrin activation and emigration across inflamed endothelium. Involvement of β(2)-integrin CD11c/CD18 in atherogenesis was recently shown in dyslipidemic mice, which motivates our study of its inflammatory function during hypertriglyceridemia in humans. METHODS AND RESULTS: Flow cytometry of blood from healthy subjects fed a standardized high-fat meal revealed that at 3.5 hours postprandial, monocyte CD11c surface expression was elevated, and the extent of upregulation correlated with blood triglycerides. Monocytes from postprandial blood exhibited an increased light scatter profile, which correlated with elevated CD11c expression and uptake of lipid particles. Purified monocytes internalized triglyceride-rich lipoproteins isolated from postprandial blood through low-density lipoprotein-receptor-related protein-1, and this also elicited CD11c upregulation. Laboratory-on-a-chip analysis of whole blood showed that monocyte arrest on a vascular cell adhesion molecule-1 (VCAM-1) substrate under shear flow was elevated at 3.5 hours and correlated with blood triglyceride and CD11c expression. At 7 hours postprandial, blood triglycerides decreased and monocyte CD11c expression and arrest on VCAM-1 returned to fasting levels. CONCLUSIONS: During hypertriglyceridemia, monocytes internalize lipids, upregulate CD11c, and increase adhesion to VCAM-1. These data suggest that analysis of monocyte inflammation may provide an additional framework for evaluating individual susceptibility to cardiovascular disease.

25 Minor Authors' reply. 2013

Ballantyne, Christie M / Bays, Harold E / Braeckman, Rene A / Soni, Paresh N. · ·Am J Cardiol · Pubmed #23317532.

ABSTRACT: -- No abstract --