Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia

Deepak L. Bhatt, P. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Steven B. Ketchum, Ralph T. Doyle, Rebecca A. Juliano, Lixia Jiao, Craig Granowitz, Jean Claude Tardif, Christie M. Ballantyne, REDUCE-IT Investigators

Research output

253 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)11-22
Number of pages12
JournalNew England Journal of Medicine
Volume380
Issue number1
DOIs
Publication statusPublished - 3 Jan 2019
Externally publishedYes

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Hypertriglyceridemia
Risk Reduction Behavior
Placebos
Triglycerides
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Confidence Intervals
Stroke
Myocardial Infarction
ethyl eicosapentaenoic acid
Atrial Flutter
Unstable Angina
Secondary Prevention
LDL Cholesterol
Atrial Fibrillation
Fasting
Cardiovascular Diseases
Hemorrhage
Mortality

Scopus subject areas

  • Medicine(all)

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Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., ... REDUCE-IT Investigators (2019). Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. New England Journal of Medicine, 380(1), 11-22. https://doi.org/10.1056/NEJMoa1812792
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. ; REDUCE-IT Investigators. / Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. In: New England Journal of Medicine. 2019 ; Vol. 380, No. 1. pp. 11-22.
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title = "Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia",
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.",
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author = "Bhatt, {Deepak L.} and Steg, {P. Gabriel} and Michael Miller and Brinton, {Eliot A.} and Jacobson, {Terry A.} and Ketchum, {Steven B.} and Doyle, {Ralph T.} and Juliano, {Rebecca A.} and Lixia Jiao and Craig Granowitz and Tardif, {Jean Claude} and Ballantyne, {Christie M.} and {REDUCE-IT Investigators}",
year = "2019",
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doi = "10.1056/NEJMoa1812792",
language = "English",
volume = "380",
pages = "11--22",
journal = "New England Journal of Medicine",
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Bhatt, DL, Steg, PG, Miller, M, Brinton, EA, Jacobson, TA, Ketchum, SB, Doyle, RT, Juliano, RA, Jiao, L, Granowitz, C, Tardif, JC, Ballantyne, CM & REDUCE-IT Investigators 2019, 'Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia', New England Journal of Medicine, vol. 380, no. 1, pp. 11-22. https://doi.org/10.1056/NEJMoa1812792

Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. / 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.; REDUCE-IT Investigators.

In: New England Journal of Medicine, Vol. 380, No. 1, 03.01.2019, p. 11-22.

Research output

TY - JOUR

T1 - Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia

AU - Bhatt, Deepak L.

AU - Steg, P. Gabriel

AU - Miller, Michael

AU - Brinton, Eliot A.

AU - Jacobson, Terry A.

AU - Ketchum, Steven B.

AU - Doyle, Ralph T.

AU - Juliano, Rebecca A.

AU - Jiao, Lixia

AU - Granowitz, Craig

AU - Tardif, Jean Claude

AU - Ballantyne, Christie M.

AU - REDUCE-IT Investigators

PY - 2019/1/3

Y1 - 2019/1/3

N2 - 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.

AB - 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.

KW - Aged

KW - Cardiovascular Diseases/mortality

KW - Double-Blind Method

KW - Drug Administration Schedule

KW - Drug Therapy, Combination

KW - Eicosapentaenoic Acid/analogs & derivatives

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use

KW - Hypertriglyceridemia/drug therapy

KW - Incidence

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Platelet Aggregation Inhibitors/therapeutic use

KW - Risk Factors

KW - Secondary Prevention

KW - Triglycerides/blood

KW - METAANALYSIS

KW - CHOLESTEROL

KW - TRIGLYCERIDES

KW - ESTER AMR101 THERAPY

KW - ATHEROSCLEROSIS

KW - INFARCTION

KW - STATIN THERAPY

KW - CORONARY-HEART-DISEASE

KW - EICOSAPENTAENOIC ACID

KW - PRIMARY PREVENTION

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UR - http://www.mendeley.com/research/trial-protocol-provided-authors-give-readers-additional-information-about-work-protocol-bhatt-dl-ste

U2 - 10.1056/NEJMoa1812792

DO - 10.1056/NEJMoa1812792

M3 - Article

C2 - 30415628

AN - SCOPUS:85058215650

VL - 380

SP - 11

EP - 22

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 1

ER -

Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. New England Journal of Medicine. 2019 Jan 3;380(1):11-22. https://doi.org/10.1056/NEJMoa1812792