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

Potential effects of icosapent ethyl on cardiovascular outcomes in cigarette smokers: REDUCE-IT smoking

Literature - Miller M, Bhatt DL, Steg PG, et al. - Eur Heart J Cardiovasc Pharmacother. 2022 Aug 11;pvac045. doi: 10.1093/ehjcvp/pvac045.

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

This post hoc analysis of data from REDUCE-IT shows that in high-risk hypertriglyceridemic patients already receiving statin therapy, treatment with IPE is associated with a similar reduction in the risk of ischemic events among current, former and never smokers, compared with placebo.

References

1. Bhatt DL, Steg PG, Miller M, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380:11-22.

Find this article online at Eur Heart J Cardiovasc Pharmacother.

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