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Evevident
Original paper
2019NEJMCardiology

REDUCE-IT

Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia

RCTResidual triglyceride risk / secondary prevention

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Overview

In statin-treated high-risk patients with elevated triglycerides, icosapent ethyl reduced major ischemic events.

Clinical takeaway

REDUCE-IT is the outcomes-positive purified EPA trial for selected statin-treated patients with elevated triglycerides. It does not generalize to over-the-counter fish oil mixtures.

Key result

Primary endpoint: 17.2% with icosapent ethyl vs 22.0% with placebo; HR 0.75.

Practice impact

Consider icosapent ethyl in selected high-risk statin-treated patients with persistently elevated triglycerides.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

8,179

Follow-up

Median 4.9 years.

Geography

Multinational

Clinical question

Does icosapent ethyl reduce cardiovascular events in statin-treated patients with elevated triglycerides and high cardiovascular risk?

Population

  • Statin-treated patients with established cardiovascular disease or diabetes plus additional risk factors, elevated triglycerides, and controlled LDL cholesterol.

Intervention

Icosapent ethyl 2 g twice daily.

Comparator

Mineral-oil placebo.

Primary outcome

Composite of cardiovascular death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina.

Icosapent ethyl reduced the primary composite ischemic endpoint compared with placebo.

Hazard ratio / 0.75 / CI 95% CI 0.68-0.83 / p=<0.001

Key results

  • Primary endpoint: 17.2% with icosapent ethyl vs 22.0% with placebo; HR 0.75; 95% CI 0.68-0.83; p<0.001.
  • Key secondary endpoint: 11.2% vs 14.8%; HR 0.74; 95% CI 0.65-0.83; p<0.001.
  • Cardiovascular death: 4.3% vs 5.2%; HR 0.80; 95% CI 0.66-0.98; p=0.03.
  • Hospitalization for atrial fibrillation or flutter was higher with icosapent ethyl: 3.1% vs 2.1%; p=0.004.
  • Serious bleeding was numerically higher: 2.7% vs 2.1%; p=0.06.

Harms

  • Hospitalization for atrial fibrillation or flutter was higher with icosapent ethyl.
  • Serious bleeding was numerically higher with icosapent ethyl.

Clinical Use

When to cite

  • When deciding whether to add icosapent ethyl for residual lipid risk despite statins.

Practice impact

  • Supports prescription icosapent ethyl for selected high-risk statin-treated patients with persistent hypertriglyceridemia.

Applicability

  • Most applicable to patients matching trial criteria: established ASCVD or diabetes with risk factors, on statins, with elevated triglycerides and controlled LDL.

Limitations

  • Used mineral-oil placebo, which has generated debate.
  • Does not apply to low-risk hypertriglyceridemia.
  • Does not support substituting generic fish-oil mixtures for icosapent ethyl.

Common misinterpretations

  • Do not generalize REDUCE-IT to over-the-counter omega-3 combinations.

Related evidence

STRENGTH - Contrasting Result

Citation

Bhatt DL, Steg PG, Miller M, et al. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019;380(1):11-22. doi:10.1056/NEJMoa1812792

The risk of ischemic events was significantly lower among those who received icosapent ethyl.