REDUCE-IT: Significant Reduction in ST-Elevation MI With Icosapent Ethyl

Presented at the ESC congress 2022 by: Prof. Deepak Bhatt, MD- Boston, MA, USA

Introduction and methods

In the REDUCE-IT trial, 70% of the enrolled patients had CVD and 30% were at high risk for CVD in a primary prevention setting (diabetes plus one additional CV risk factor). All patients had mildly elevated triglycerides (135-500 mg/dL) and well-controlled LDL-c (40-100 mg/dL [1-2.6 mmol/L]) on statin therapy. ~8000 Patients were randomized to icosapent ethyl (2 grams twice a day) or to a matching mineral oil placebo (colorless and odorless). Mean follow-up was 4.9 years.

The primary composite endpoint -time to first occurrence of CV death, non-fatal MI, non-fatal stroke, coronary revascularization or unstable angina requiring hospitalization (5-point MACE) – was reduced by 25% in the icosapent ethyl group compared with the placebo group (HR 0.75, 95%CI:0.68-0.83). A similar risk reduction was seen with icosapent ethyl for the key secondary composite endpoint of CV death, MI or stroke.

Main results

• A significant reduction in overall myocardial infarction was observed with icosapent ethyl compared with placebo (HR 0.69, 95%CI: 0.58-0.81, P=0.000005).
• This benefit was observed early, with consistent statistical significance by 26 months.
• Incidence of STEMI was 3.9% in the placebo group vs. 2.7% in the icosapent ethyl group, resulting in an HR of 0.60 (95%CI:0.44-0.81, P=0.0008) and incidences of NSTEMI were 7.8% in the placebo group and 5.9% in the icosapent ethyl group (HR 0.73, 95%CI:0.60-0.89, P=0.001).
• In patients who experienced STEMI (n=110) or NSTEMI (n=246), number of patients with at least one bleeding event appeared to be higher in the icosapent ethyl group compared with the placebo group, but this was not statistically different.
• When looking at different subtypes of MI, a consistent benefit with icosapent ethyl was observed.
• Examination of size of MIs (assessed by fold elevation in troponin) showed a consistent significant reduction in the outcome from small to large MIs (P=0.000008 for trend of greater benefit with icosapent ethyl on larger MIs).
• Overall tolerability and adverse event patterns with icosapent ethyl in patients who experienced STEMI or NSTEMI were consistent with the full study.
• AF/flutter events were more prevalent in the icosapent ethyl group compared with the placebo group, but this was not statistically significant.
• There was a relationship between on treatment levels of EPA and lower rates of MI.

Conclusion

This analysis of REDUCE-IT showed that treatment with icosapent ethyl 4 g/day significantly reduced MI overall and MI subtypes, including STEMI, NSTEMI, MI leading to cardiac arrest and resuscitated MI. There was no significant increase in serious bleeding. Furthermore, icosapent ethyl reduced all sizes of MI, also large MI types.

• Our reporting is based on the information provided at the ESC Congress -