What is the role of Vasepa (icosapent ethyl) in managing hypertriglyceridemia?

Role of Vascepa (Icosapent Ethyl) in Managing Hypertriglyceridemia

Icosapent ethyl (Vascepa) is recommended as an adjunct to diet to reduce triglyceride levels in adults with severe hypertriglyceridemia (≥500 mg/dL) and can be considered for cardiovascular risk reduction in patients with established atherosclerotic cardiovascular disease (ASCVD) or other cardiovascular risk factors who have controlled LDL-C but elevated triglycerides (135-499 mg/dL) on statin therapy. 1, 2

Indications for Use

Severe Hypertriglyceridemia (≥500 mg/dL)

• FDA-approved as an adjunct to diet to reduce triglyceride levels in adult patients with severe hypertriglyceridemia (≥500 mg/dL) 2
• Recommended dosage is 4 grams per day, taken as either four 0.5 gram capsules twice daily with food or two 1 gram capsules twice daily with food 2
• Helps reduce the risk of pancreatitis, although the FDA label notes that the effect on pancreatitis risk has not been definitively determined 2

Moderate Hypertriglyceridemia with Additional Risk Factors

• In patients with ASCVD or other cardiovascular risk factors on statin therapy with controlled LDL-C but elevated triglycerides (135-499 mg/dL), icosapent ethyl can be considered to reduce cardiovascular risk 1
• The REDUCE-IT trial demonstrated a 25% relative risk reduction in the composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina 1
• Cardiovascular death was reduced by 20% (P = 0.03) in the REDUCE-IT trial 1

Mechanism of Action and Unique Properties

• Icosapent ethyl is a high-purity ethyl ester of eicosapentaenoic acid (EPA) that is de-esterified to EPA following oral administration 3
• Unlike other omega-3 fatty acid products that contain both EPA and docosahexaenoic acid (DHA), icosapent ethyl contains ≥96% EPA ethyl ester and does not contain DHA 3
• This is clinically significant because DHA has been associated with increased LDL-C levels, whereas icosapent ethyl does not increase LDL-C 3

Clinical Evidence

REDUCE-IT Trial

• Enrolled 8,179 adults on statin therapy with moderately elevated triglycerides (135-499 mg/dL) who had either established cardiovascular disease or diabetes plus at least one other cardiovascular risk factor 1
• Demonstrated a 25% relative risk reduction for the primary composite endpoint of cardiovascular events 1
• The composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was reduced by 26% 1
• Important to note that these results should not be extrapolated to other omega-3 fatty acid products 1

ANCHOR Study

• In statin-treated patients with triglycerides 200-499 mg/dL, icosapent ethyl 4 g/day significantly reduced:
  • Triglycerides by 20% 4
  • Non-HDL cholesterol by 12.3% 4
  • Apolipoprotein B by 7.4% 4
  • Lipoprotein-associated phospholipase A2 by 19.6% 4
  • High-sensitivity C-reactive protein by 17.9% 4
• Did not increase LDL-C levels 4, 5
• Improved lipoprotein particle concentration and size 6
• Reduced markers of inflammation 7

Differentiating from Other Triglyceride-Lowering Therapies

• Unlike fibrates and niacin, which have not shown cardiovascular benefit when added to statins, icosapent ethyl has demonstrated significant cardiovascular risk reduction 1
• Guidelines specifically note that statin plus fibrate combination therapy has not been shown to improve ASCVD outcomes and is generally not recommended 1
• Similarly, statin plus niacin combination therapy has not shown additional cardiovascular benefit above statin therapy alone and may increase stroke risk 1
• Results from the REDUCE-IT trial should not be extrapolated to other omega-3 fatty acid products 1

Safety Considerations

• Common adverse reactions (incidence ≥3% and ≥1% more frequent than placebo) include musculoskeletal pain, peripheral edema, constipation, gout, and atrial fibrillation 2
• Increased risk of atrial fibrillation/flutter requiring hospitalization, particularly in patients with a previous history of these conditions 2
• Potential for allergic reactions in patients with fish allergy 2
• Increased risk of bleeding, especially in patients receiving concomitant antithrombotic medications 2

Practical Approach to Management

1. For patients with severe hypertriglyceridemia (≥500 mg/dL):

   • First address lifestyle factors, secondary causes, and medications that raise triglycerides 1
   • Consider icosapent ethyl 4 g/day as an adjunct to diet to reduce triglyceride levels 2

2. For patients with moderate hypertriglyceridemia (135-499 mg/dL):

   • Optimize statin therapy first 1
   • If patient has ASCVD or other cardiovascular risk factors and triglycerides remain elevated despite controlled LDL-C on statin therapy, consider adding icosapent ethyl 4 g/day 1

3. Administration:

   • Administer as 2 grams twice daily with food 2
   • Advise patients to swallow capsules whole and not to break, crush, dissolve, or chew them 2

Key Distinction from Other Omega-3 Products

It's critical to recognize that the cardiovascular benefits demonstrated in the REDUCE-IT trial are specific to icosapent ethyl and should not be extrapolated to other omega-3 fatty acid products 1. This distinction is important when selecting appropriate therapy for patients with hypertriglyceridemia.