Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia.
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled trial
PubMed 30415628 · doi:10.1056/NEJMoa1812792
What was done
In a multicenter, double-blind trial (REDUCE-IT), 8,179 patients with established cardiovascular disease (70.7%) or diabetes with additional risk factors who were receiving statin therapy (fasting triglycerides 135–499 mg/dL, LDL-C 41–100 mg/dL) were randomized to receive icosapent ethyl (2 g twice daily, 4 g/day) or placebo. Patients were followed for a median of 4.9 years. The primary composite endpoint was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina.
What was found
The primary composite endpoint occurred in 17.2% of the icosapent ethyl group compared to 22.0% in the placebo group (HR 0.75; 95% CI, 0.68 to 0.83; P<0.001). The key secondary endpoint (CV death, nonfatal MI, or nonfatal stroke) occurred in 11.2% versus 14.8% (HR 0.74; 95% CI, 0.65 to 0.83; P<0.001). Cardiovascular death was significantly reduced (4.3% vs. 5.2%; HR 0.80; 95% CI, 0.66 to 0.98; P=0.03). Hospitalization for atrial fibrillation or flutter was significantly higher with icosapent ethyl (3.1% vs. 2.1%, P=0.004), while serious bleeding occurred in 2.7% versus 2.1% (P=0.06).
Why it matters
This trial established that high-dose purified EPA (icosapent ethyl) provides substantial residual cardiovascular risk reduction in statin-treated patients with elevated triglycerides and high cardiovascular risk.
Limits
The study was restricted to high-risk individuals on statin therapy with mild-to-moderate hypertriglyceridemia (70.7% secondary prevention), limiting generalizability to primary prevention or lower-risk cohorts. Icosapent ethyl treatment was associated with a statistically significant increase in hospitalizations for atrial fibrillation or flutter, and a numerically higher rate of serious bleeding events.
Cited by
- supports In the REDUCE-IT trial, participants taking 4 grams of Vascepa per day had approximately a 25% lower risk of cardiovascular events, death, and ischemic events over 5 years.