Is it appropriate to add Vascepa (icosapent ethyl) to the treatment regimen?

Should You Add Vascepa (Icosapent Ethyl)?

Yes, add Vascepa (icosapent ethyl) 4 g/day if your patient has established cardiovascular disease OR diabetes with additional risk factors, is on statin therapy with controlled LDL-C (41-100 mg/dL), and has persistently elevated triglycerides (≥135 mg/dL). 1

Patient Eligibility Criteria

You should add Vascepa if ALL of the following are met:

• Patient has established ASCVD (secondary prevention) OR diabetes mellitus plus ≥1 additional cardiovascular risk factor (primary prevention) 1, 2
• Currently on statin therapy with LDL-C controlled between 41-100 mg/dL 1
• Fasting triglycerides remain elevated at 135-499 mg/dL despite statin therapy 1
• Patient has optimized lifestyle modifications (diet, weight loss, alcohol reduction) 1

The American Heart Association specifically states that icosapent ethyl should be considered first-line therapy for patients with type 2 diabetes and coronary artery disease whose triglycerides remain elevated (>135 mg/dL) despite maximally tolerated statin and lifestyle changes. 1

Evidence for Cardiovascular Benefit

The REDUCE-IT trial demonstrated robust cardiovascular outcomes that prioritize mortality and morbidity:

• 25% relative risk reduction in the primary composite endpoint (cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina) with number needed to treat of 21 1
• 26% reduction in the key secondary endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke 1
• 20% reduction in cardiovascular mortality specifically 1
• Benefits were consistent in patients with diabetes (HR 0.77) and without diabetes (HR 0.73) 1

The American Diabetes Association and American College of Cardiology have incorporated these findings into their guidelines, recommending icosapent ethyl for cardiovascular risk reduction in this population. 1

Dosing and Administration

Prescribe icosapent ethyl 2 g twice daily (total 4 g/day) with food. 1, 2 This is the FDA-approved dose that demonstrated cardiovascular benefit in REDUCE-IT. 3, 2

Expected Effects on Lipid Parameters

With icosapent ethyl 4 g/day, expect:

• Median triglyceride reduction of approximately 19-20% 1
• No increase in LDL-C (critical advantage over other omega-3 products) 1, 4
• Reduction in non-HDL-C by approximately 13% 1
• Reduction in inflammatory markers including hs-CRP 1, 4
• Increase in EPA levels from ~26 to ~144 μg/mL 1

Critical Safety Considerations and Monitoring

Monitor for atrial fibrillation/flutter: The risk increased from 2.1% with placebo to 3.1% with icosapent ethyl (P=0.004). 1 Screen patients with symptoms of palpitations, irregular heartbeat, or lightheadedness.

Monitor for bleeding: Serious bleeding events occurred in 2.7% versus 2.1% with placebo (P=0.06), though no fatal bleeding occurred. 1, 2 Use caution in patients on anticoagulation or with bleeding disorders.

Assess for fish/shellfish allergy before prescribing, as this is a contraindication. 3

Important Distinctions from Other Omega-3 Products

Do NOT extrapolate REDUCE-IT results to other omega-3 fatty acid products. 1 The STRENGTH trial using a different omega-3 carboxylic acid formulation (containing both EPA and DHA) showed NO cardiovascular benefit (HR 0.99, P=0.84). 1 Icosapent ethyl is a high-purity EPA ethyl ester (≥96% EPA) without DHA, which distinguishes it from mixed omega-3 products. 5, 6

When NOT to Use Vascepa

Do not add Vascepa if:

• Triglycerides are <135 mg/dL (no evidence of benefit) 1
• LDL-C is not controlled on statin therapy (optimize LDL-lowering first) 1
• Patient has severe hypertriglyceridemia ≥500 mg/dL requiring acute pancreatitis prevention (consider fibrates instead) 1, 7
• Known hypersensitivity to icosapent ethyl or fish/shellfish 3

Combination Therapy Considerations

Vascepa can be safely combined with statins and has a similar safety profile to placebo when added to background statin therapy. 1, 2 Unlike fibrate-statin combinations, which increase myopathy risk and have not shown cardiovascular benefit, icosapent ethyl demonstrated clear cardiovascular mortality reduction. 1

Avoid combining statins with fibrates or niacin for cardiovascular risk reduction, as these combinations have not shown cardiovascular benefit and may increase adverse effects. 1