Icosapent ethyl reduces MACE in ASCVD, irrespective of baseline CVD risk

In an analysis of REDUCE-IT among patients with ASCVD, icosapent ethyl reduced the risk of MACE across all baseline CVD risk quartiles compared with placebo.

This summary is based on the publication of Burger PM, Bhatt DL, Dorresteijn JAN, et al. - Effects of icosapent ethyl according to baseline residual risk in patients with atherosclerotic cardiovascular disease: results from REDUCE-IT. Eur Heart J Cardiovasc Pharmacother. 2024 Apr 27:pvae030. doi: 10.1093/ehjcvp/pvae030.

Introduction and methods

Background

In REDUCE-IT, treatment with icosapent ethyl versus placebo reduced the risk of MACE in statin-treated patients with elevated triglyceride levels and established CVD or elevated CVD risk [1]. According to clinical guidelines, icosapent ethyl may be considered to reduce CVD risk in high-risk patients with ASCVD and elevated triglycerides despite optimal statin treatment [2-5]. It remains unclear whether there is heterogeneity in the treatment effect of icosapent ethyl across individuals with ASCVD.

Aim of the study

The aim of this study was to evaluate the relative and absolute treatment effects of icosapent ethyl on MACE according to individual baseline CVD risk in patients with ASCVD.

Methods

The REDUCE-IT trial was an international, double-blind, placebo-controlled trial in which 8179 statin-treated patients with established CVD or with diabetes and at least one additional risk factor, elevated triglycerides (150-499 mg/dL [1.69-5.63 mmol/L]) and controlled LDL-c levels (41-100 mg/dL [1.06-2.59 mmol/L]) were randomized to IPE 4 g/day or placebo. The current analysis included all participants of REDUCE-IT with established ASCVD (n=5785). The authors used the ESC-guideline recommended SMART2 and SMART-REACH risk models to predict 5-year and lifetime CVD risk, respectively, in patients with ASCVD [2, 6-7]. The study population was divided into quartiles depending on the predicted baseline 5-year risk of 3-point MACE (mean predicted risk was 9.0%, 13.7%, 19.3% and 33.7% in risk quartile 1 to 4, respectively). The median follow-up period was 4.8 years (IQR: 3.2-5.3).

Outcomes

The primary outcome was 3-point MACE, a composite of CV death, non-fatal MI or non-fatal stroke. The secondary outcome was 5-point MACE, a composite of CV death, non-fatal MI, non-fatal stroke, coronary revascularization, or unstable angina.

Main results

• In patients with ASCVD, icosapent ethyl versus placebo reduced the risk of 3-point MACE (HR: 0.72; 95%CI: 0.63-0.82; absolute risk reduction (ARR): 4.4%; NNT: 23) and 5-point MACE (HR: 0.73; 95%CI: 0.65-0.81; ARR: 6.2%; NNT: 16).
• There was no difference in the relative treatment effects of icosapent ethyl across CVD risk quartiles (P for interaction=0.106 for 3-point MACE; and P for interaction=0.133 for 5-point MACE).
• The absolute treatment effects of icosapent ethyl on 3-point MACE increased across risk quartiles (ARR: 3.9% and NNT: 26 for risk quartile 1; ARR: 4.3% and NNT: 24 for risk quartile 2; ARR: 5.1% and NNT: 20 for risk quartile 3; and ARR: 5.6% and NNT: 18 for risk quartile 4).
• The absolute risk reductions with icosapent ethyl on 5-point MACE across risk quartiles were 6.3%, 7.9%, 4.9% and 6.5%, respectively.
• The absolute lifetime benefit (gains in MACE-free survival) from treatment with icosapent ethyl ranged from 3.9 years (IQR: 3.4-4.4) in the lowest quartile to 1.9 years (IQR: 1.5-2.2) in the highest quartile for 3-point MACE.

Conclusion

In this analysis of REDUCE-IT among ASCVD patients with elevated triglycerides, icosapent ethyl reduced the risk of MACE irrespective of baseline CVD risk. The absolute treatment benefit increased with increasing CVD risk, but was already substantial in patients in the lowest risk quartile. The expected lifetime benefit of icosapent ethyl was the greatest in lower-risk patients. The authors highlight that “[t]hese results may support a broader use of icosapent ethyl than currently recommended by the ESC and AHA/ACC guidelines, and expert consensus documents.”

Find this article online at Eur Heart J Cardiovasc Pharmacother.

References

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