Icosapent ethyl reduces first and total stroke in patients with or high risk of CVD

Reduction in Ischemic Stroke With Icosapent Ethyl - Insights From REDUCE-IT

Presented at the International Stroke Conference 2021 by Deepak Bhatt (Boston, MA, USA)

Introduction and methods

In the REDUCE-IT trial, >8000 patients were enrolled of whom ~70% were secondary prevention patients and ~30% diabetes patients with at least one CV risk factor. Patients were randomized to icosapent ethyl 4 gr/day or placebo. Triglyceride levels had to be between 150-500 mg/dL and LDL-c between 40 and 100 mg/dL and patients were required be treated with a statin. Mean follow-up was ~5 years. Primary endpoint of the trial was time to first occurrence of composite of CV death, non-fatal MI, non-fatal stroke, coronary revascularization or unstable angina requiring hospitalization (5p MACE). Results of the main trial showed a 25% reduction of the primary outcome with icosapent ethyl compared to placebo. The key secondary composite endpoint of CV death, MI and stroke was also reduced by icosapent ethyl compared to placebo. Prespecified hierarchical testing showed that several endpoints were reduced, including first event of fatal or nonfatal stroke (a 28% reduction). Furthermore, analysis of total events (first and subsequent) showed a reduction of 31% in total events in the icosapent ethyl group compared to the placebo group.

In this analysis, additional prespecified and post hoc stroke endpoints in the REDUCE-IT trial were examined.

Main results

• Rate of first fatal or nonfatal stroke was 2.9% in the icosapent ethyl group and 4.3% in the placebo group (HR 0.72, 95%CI: 0.55-0.93, P=0.01), resulting in relative risk reduction of 28%, absolute risk reduction of 0.9% and NNT of 114.
• Icosapent ethyl also reduced total strokes; event rate was 3.5% in the icosapent ethyl group and 5.1% in the placebo group (RR 0.68, 95%CI: 0.52-0.91, P=0.008).
• Consistent reductions by icosapent ethyl were observed for nonfatal and fatal stroke.
• Event rates for ischemic stroke were 2.0% in the icosapent ethyl group and 3.0% in the placebo group (HR 0.64, 95%CI: 0.49-0.85, P=0.002). No difference in rates for hemorrhagic stroke were observed (0.3% for icosapent ethyl vs. 0.2% for placebo).
• Icosapent ethyl reduced total ischemic strokes (event rate was 2.9% in the icosapent ethyl group and 4.5% in the placebo group, RR 0.64, 95%CI: 0.47-0.86, P=0.003).
• Subgroup analysis for total ischemic strokes showed a consistent benefit with icosapent ethyl across all groups, independent of risk stratum, region, statin use, demographics, disease characteristics, or biomarker levels.
• In the main trial, no differences were seen between icosapent ethyl and placebo in overall tolerability or adverse events. More bleeding was observed with icosapent ethyl vs. placebo, but no significant difference in hemorrhagic stroke. More AF/flutter was seen with icosapent ethyl compared to placebo.

Conclusion

Icosapent ethyl 4 g/day reduces first and total strokes compared to placebo in patients with or at high risk of CVD, who are treated with statins. Moreover, icosapent ethyl reduced first and total ischemic strokes compared to placebo, without an increase in hemorrhagic stroke. The authors suggest that EPA-based therapy with icosapent ethyl represents a novel approach to reduce stroke.

- Our reporting is based on the information provided during ISC 2021 –