Icosapent ethyl: safely reducing cardiovascular risk in adults with elevated triglycerides

Figures & data

Figure 1. Distinct membrane interactions and tissue distributions of eicosapentaenoic acid and docosahexaenoic acid.

Abbreviations: DHA = docosahexaenoic acid, EPA = eicosapentaenoic acid.

Table 1. Treatment-emergent adverse events in Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) [100]

	Icosapent ethyl (N = 4089)	Placebo (N = 4090)	P-value for difference
Subjects with ≥1 TEAE	3343 (81.8%)	3326 (81.3%)	0.63
TEAE leading to study drug withdrawal	321 (7.9%)	335 (8.2%)	0.60
Serious TEAE	1252 (30.6%)	1254 (30.7%)	0.98
Serious TEAE leading to study drug withdrawal	88 (2.2%)	88 (2.2%)	1.00
Serious TEAE leading to death	94 (2.3%)	102 (2.5%)	0.61

Abbreviation: TEAE = treatment-emergent adverse event.

Table 2. Key completed randomized controlled trials of eicosapentaenoic acid

Study	Main Inclusion Criteria	Intervention	Control	Sample Size	Primary Endpoint	Primary Follow-Up Duration
JELIS [91]	Age 50–75 years (men) or postmenopausal to 75 years (women) + With or without coronary artery disease + TC ≥6.5 mmol/l (LDL-C ≥4.4 mmol/l)	EPA ethyl ester 600 mg thrice daily + pravastatin ≥10 mg daily or simvastatin ≥5 mg daily	Pravastatin ≥10 mg daily or simvastatin ≥5 mg daily	18,645	A composite of any major coronary event, including sudden cardiac death, fatal and non-fatal myocardial infarction, and other non-fatal events including unstable angina pectoris, angioplasty, stenting, or coronary artery bypass grafting	4.6 years
CHERRY [95]	Age ≥20 years + Stable angina pectoris or Acute coronary syndrome + TC ≥220 mg/dl or LDL-C ≥140 mg/dl or Cholesterol-lowering deemed necessary when LDL-C ≥100 mg/dl or TC ≥180 mg/dl + Coronary plaque Successful percutaneous coronary intervention with intravascular ultrasound guidance	EPA 1800 mg daily + pitavastatin 4 mg daily	Pitavastatin 4 mg daily	193	Change in coronary plaque tissue characteristics as evaluated by integrated backscatter intravascular ultrasound	6–8 months
MARINE [96]	Age ≥18 years + TG 500–2000 mg/dl	Icosapent ethyl 1 gram twice daily or 2 grams twice daily	Placebo	229	Placebo-corrected median percentage of change in TG from baseline	12 weeks
ANCHOR [97]	Age ≥18 years + High risk for coronary heart disease On statin therapy + TG 200–499 mg/dl LDL-C 40–99 mg/dl	Icosapent ethyl 1 gram twice daily or 2 grams twice daily	Placebo	702	Placebo-corrected median percentage of change in TG from baseline	12 weeks
REDUCE-IT [100]	Age ≥45 years (established cardiovascular disease) or Age ≥50 years (diabetes and an additional risk factor) + TG 135–499 mg/dl LDL-C 41–100 mg/dl On statin therapy	Icosapent ethyl 2 grams twice daily	Placebo	8179	A composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or unstable angina	4.9 years

Abbreviations: EPA = eicosapentaenoic acid, LDL-C = low-density lipoprotein cholesterol concentration, TC = total cholesterol concentration, TG = triglyceride concentration.

Table 3. Additional randomized controlled trials of triglyceride lowering medications

Study	Main Inclusion Criteria	Intervention	Control	Sample Size	Primary Endpoint	(Expected) Primary Follow-Up Duration
EVAPORATE [113]	Age 30–85 years + TG 200–499 mg/dl LDL‐C ≥40 and ≤115 mg/dl on statin therapy + Stenosis of ≥20% in one coronary artery by invasive angiography or MDCTA	Icosapent ethyl 2 grams twice daily	Placebo	80	Rate of change in low‐attenuation plaque volume from baseline to final assessment as measured by MDCTA	18 months
RESPECT-EPA [116]	Age 20–79 years + On statin therapy + Established coronary artery disease	EPA 1800 mg once daily	None	3900	A composite of cardiovascular death, non-fatal myocardial infarction, non-fatal cerebral infarction, unstable angina requiring emergent hospitalization and coronary revascularization, or coronary revascularization	5 years
STRENGTH [117]	Age ≥18 years (established cardiovascular disease) or Age ≥40 years (men) or ≥50 years (women) (diabetes with an additional risk factor) or Age >50 years (men) or >60 years (women) (with an additional risk factor) + LDL-C <100 mg/dl or LDL-C ≥100 if treated with high-intensity or maximally tolerated statin TG 180–500 mg/dl and HDL-C < 42 mg/dl (men) or <47 mg/dl (women)	EPA + DHA carboxylic acids 4 grams once daily	Placebo	13,078	A composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina	3.5 years
OMEMI [121]	Age 70–82 years + Type 1, 2, or 4 myocardial infarction within 2–8 weeks	EPA+DHA 600 mg thrice daily	Placebo	1027	A composite of total mortality, first non-fatal recurring myocardial infarction, stroke, or revascularization	2 years
PROMINENT [120]	Age ≥18 years (established cardiovascular disease) or Age ≥50 years (men) or ≥55 years (women) (no established cardiovascular disease) + Type 2 diabetes TG level 200–499 mg/dl HDL-C level ≤40 mg/dl + On moderate-to-high intensity statin therapy or LDL-C ≤70 mg/dl or Statin intolerant and LDL-C ≤100 mg/dl	Pemafibrate 0.2 mg twice daily	Placebo	10,391	A composite of non-fatal myocardial infarction, non-fatal ischemic stroke, hospitalization for unstable angina requiring urgent coronary revascularization, or cardiovascular death	5 years

Abbreviations: DHA = docosahexaenoic acid, EPA = eicosapentaenoic acid, HDL-C = high-density lipoprotein cholesterol concentration, LDL-C = low-density lipoprotein cholesterol concentration, MDCTA = multi‐detector computed tomography angiography, TG = triglyceride concentration.

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