Icosapent ethyl decreases CVD risk after MI

Introduction and methods

Background

Despite the variety of treatment options to lower LDL-c and triglyceride levels, it has proven difficult to fully eliminate CVD risk. However, this is of great importance in patients with prior MI, who have an increased risk of recurrent ischemic events [1]. Recently, icosapent ethyl (IPE) has emerged as an additive agent to further reduce CVD risk. This ethyl ester of eicosapentaenoic acid (an omega-3 fatty acid) reduces plaque volume and mitigates inflammation, among others [2-8].

Aim of the study

The authors assessed the effect of IPE on ischemic events in statin-treated patients with prior MI and hypertriglyceridemia.

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Methods

This was a post-hoc analysis of REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl – Intervention Trial), a multinational, double-blind, phase 3b RCT in which 8179 statin-treated patients with established CVD or diabetes mellitus plus other risk factors were randomized to IPE (2 g twice daily) or placebo [9]. Patients had to have controlled LDL-c levels and moderately elevated triglyceride levels at baseline. Of the 8179 patients in REDUCE-IT, 3693 (45%) had a history of MI, of whom 1870 had received IPE and 1823 placebo. Their median follow-up time was 4.8 years (IQR: 3.2–5.3).

Outcomes

The primary endpoint was defined as a composite outcome of CV death, nonfatal MI, nonfatal stroke, coronary revascularization, and unstable angina requiring hospitalization. The key secondary endpoint was the composite of CV death, nonfatal MI, and nonfatal stroke. Additional prespecified, blindly adjudicated endpoints included some of the individual component of the primary endpoint, as well as sudden cardiac death and cardiac arrest.

Main results

Primary endpoint

• In patients with prior MI, IPE treatment significantly reduced the incidence of the primary composite endpoint from 26.1% to 20.2% compared with placebo (hazard ratio (HR): 0.74; 95% CI: 0.65–0.85; P = 0.00001), equating to a relative risk reduction (RRR) of 26%.
• The absolute risk reduction (ARR) in the primary endpoint was 5.9%.
• History of coronary revascularization had no effect on the primary endpoint.

Key secondary endpoint

• IPE also significantly reduced the incidence of the key secondary composite endpoint from 18.0% to 13.3% compared with placebo (HR: 0.71; 95% CI: 0.61–0.84; P = 0.00006), indicating an RRR of 29%.
• The ARR in the key secondary endpoint was 4.7%.
• Similar reductions in the key secondary endpoint were observed upon stratification by history of coronary revascularization.

Additional endpoints

• Significant RRRs for IPE versus placebo were also seen in cardiac arrest (56%), sudden cardiac death (40%), total ischemic events (35%), fatal or nonfatal MI (34%) and CV death (30%). The RRR for all-cause mortality was 20%(P = 0.054).

Safety

• The incidence of hospitalization for atrial fibrillation was significantly higher in IPE-treated patients than in the placebo group (3.6% vs. 2.2%; log-rank P = 0.01).
• The bleeding rate was significantly higher in IPE-treated than in placebo-treated patients (10.6% vs. 8.7%; Fisher’s exactP = 0.05), but there was no significant difference in the frequency of serious bleeding (2.7% vs 2.2%; Fisher exact’s P = 0.46).

Conclusion

References

Find this article online at J Am Coll Cardiol.