Similar benefit of icosapent ethyl in subgroups of patients based on smoking status

Introduction and methods

Background

REDUCE-IT showed that icosapent ethyl (IPE), a highly purified ethyl ester of the omega-3 fatty acid eicosapentaenoic acid with antithrombotic properties, lowers the risk of ischemic events by 25% in high-risk patients with hypertriglyceridemia already receiving statin therapy [1]. It is unclear whether IPE can reduce the risk of ischemic events attributable to smoking in this patient group.

Aim of the study

This post hoc analysis of data from REDUCE-IT investigated whether IPE can reduce the risk of ischemic events attributable to smoking in high-risk patients with hypertriglyceridemia already receiving statin therapy.

Methods

The researchers conducted a post hoc analysis of data from REDUCE-IT. In this multicenter, double-blind, placebo-controlled phase 3b study, 8179 adults ≥45 years with CVD or ≥50 years with diabetes and 1 or more additional cardiovascular risk factors were randomized to twice-daily IPE 2 g or placebo. Inclusion criteria were a fasting triglyceride level of 1.52-5.63 mmol/l, an LDL-c level of 1.06-2.59 mmol/l and stable statin therapy for at least 4 weeks before study entry. The median follow-up period was 4.9 years. In this post-hoc analysis, patients were stratified by smoking status, defined as ‘current smokers’ (i.e., within the past 30 days), ‘former smokers’ or ‘never smokers’.

Outcomes

The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization and hospitalization for unstable angina. The key secondary outcome was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke. The investigators were also interested in time to first ischemic event and total number of ischemic events (i.e., first and subsequent events).

Main results

Primary outcome

• Compared with placebo, treatment with IPE resulted in a reduction in time to first ischemic event of the primary composite endpoint among current smokers (n=1241; HR: 0.79; 95%CI: 0.62-1.00; P=0.05; ARR: 4.7; NNT: 21), former smokers (n=3672; HR: 0.76; 95%CI: 0.68-0.88; P=0.0002) and never smokers (n=3264; HR: 0.72; 95%CI: 0.61-0.85; P<0.0001) (P-interaction=0.79).
• Compared with placebo, treatment with IPE resulted in a reduction in total number of events of the primary composite endpoint among current smokers (n=1241; rate ratio: 0.74; 95%CI: 0.55-0.99; P=0.04) and never smokers (n=3264; rate ratio: 0.65; 95%CI: 0.53-0.80; P<0.0001).
• Among current and former smokers combined (n=4913), treatment with IPE resulted in a reduction in time to first ischemic event (HR: 0.77; 95%CI: 0.68-0.87; P<0.0001; ARR: 4.9; NNT: 20) and total number of events (rate ratio: 0.71; 95%CI: 0.61-0.82; P<0.0001) of the primary composite endpoint, compared with placebo.
• The cumulative incidence rates of ischemic events of the primary composite endpoint were similar in the IPE-treated current smokers (23.8%) and former smokers (23.0%) as in placebo-treated never smokers (25.7%).

Key secondary outcome

• Compared with placebo, treatment with IPE resulted in a reduction in time to first ischemic event of the key secondary composite endpoint among current smokers (n=1241; HR: 0.74; 95%CI: 0.56-0.99; P=0.04), former smokers (n=3672; HR: 0.77; 95%CI: 0.64-0.92; P=0.005) and never smokers (n=3264; HR: 0.69; 95%CI: 0.56-0.84; P=0.0002) (P-interaction=0.65).
• Among current and former smokers combined (n=4913), treatment with IPE resulted in a reduction in time to first ischemic event (HR: 0.77; 95%CI: 0.66-0.89; P=0.0006) and total number of events (rate ratio: 0.74; 95%CI: 0.62-0.88; P=0.0006) of the key secondary composite endpoint, compared with placebo.

Conclusion

References

Find this article online at Eur Heart J Cardiovasc Pharmacother.