Icosapent ethyl with statin therapy for reducing the risk of cardiovascular events in people with raised triglycerides

NICE state:

Icosapent ethyl is recommended as an option for reducing the risk of cardiovascular events in adults. It is recommended if they have a high risk of cardiovascular events and raised fasting triglycerides (1.7 mmol/litre or above) and are taking statins, but only if they have:

• established cardiovascular disease (secondary prevention), defined as a history of any of the following:
  • acute coronary syndrome (such as myocardial infarction or unstable angina needing hospitalisation)
  • coronary or other arterial revascularisation procedures
  • coronary heart disease
  • ischaemic stroke
  • peripheral arterial disease, and
• low-density lipoprotein cholesterol (LDL-C) levels above 1.04 mmol/litre and below or equal to 2.60 mmol/litre.

Evidence for the use of icosapent ethyl is from the REDUCE-IT trial:

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.

• 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)
• patients were randomly assigned to receive 2 g of icosapent ethyl (icosapent ethyl or ethyl eicosapentaenoic acid is a synthetic derivative of the omega-3 fatty acid eicosapentaenoic acid) 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
  • key secondary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke
  • 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)
    • a 25% lower risk in the icosapent ethyl group
  • 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)
    
    
• study authors concluded that "..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.."

A review notes (3):

• one study of people taking a statin who had CV disease or were at high risk of CV disease, the risk of ischaemic events was 17.2% with icosapent ethyl compared with 22.0% with a placebo consisting of mineral oil.
• adverse events include bleeding, atrial flutter or fibrillation, constipation, gout, musculoskeletal pain, peripheral oedema and rash.
• t.he National Institute for Health and Care Excellence found that icosapent ethyl was not cost-effective for primary prevention but recommended it as an option for secondary prevention of CV disease

Reference:

1. NICE (July 2022). Icosapent ethyl with statin therapy for reducing the risk of cardiovascular events in people with raised triglycerides
2. Bhart DL et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia.N Engl J Med. 2018 Nov 10.
3. Icosapent ethyl for CV risk reductionDrug and Therapeutics Bulletin 2024;62:135-140