Convincing evidence of the role of icosapent in reducing subsequent CV events

A recent analysis of the REDUCE-IT trial has demonstrated that icosapent ethyl 2 g twice daily was superior to placebo in reducing triglycerides (TGs), cardiovascular (CV) events, and CV death among patients with high TGs and high cardiovascular risk [1].

Previous results from the REDUCE-IT showed that icosapent ethyl reduced the risk of a first ischaemic event by 25% (i.e. the primary composite endpoint of CV death, myocardial infarction, stroke, coronary revascularisation, or hospitalisation for unstable angina) [2]. The current REDUCE-IT analysis presented by Prof. Deepak Bhatt (Brigham and Women’s Hospital, USA) examined total ischaemic events.

The aim of the multicentre, randomised, double-blind REDUCE-IT trail was to assess the safety and benefit of icosapent ethyl compared with placebo in reducing total CV events among patients with high triglycerides. The study was set up by randomising 8,179 eligible patients 1:1 to either icosapent ethyl (2 g twice daily with food) (n=4,089) or matching placebo (n=4,090). Patients needed to be aged >45 years with established CV disease or age >50 years with diabetes and ≥1 additional risk factor, fasting TG level between 135-499 mg/dL, low-density lipoprotein (LDL) cholesterol level between 41 and 100 mg/dL, and stable dose of statin for ≥4 weeks in order to be eligible for inclusion. Mean patient age was 64.0 years and 28% was female. Median baseline TG was 216 mg/dL, and median baseline LDL-cholesterol was 75 mg/dL); 71% had a history of atherosclerosis and 29% had diabetes mellitus.

After a median follow-up of 4.9 years, 55.2% first primary endpoint events and 44.8% of subsequent primary endpoint events occurred. The total number of primary endpoint events was reduced with icosapent ethyl: this was 61 vs 89 per 1,000 patient years for icosapent ethyl vs placebo, respectively (RR 0.70; 95% CI, 0.62-0.78; P<0.0001). For second events, a further 32% reduction was seen as well as a 31% reduction of third events and a 48% reduction in fourth or subsequent events (total events reduction 30% when compared to placebo).

Each component of the primary composite endpoint was also reduced with icosapent ethyl as well as the total key secondary endpoint events (32 vs 44 per 1,000 patient years for icosapent ethyl vs placebo, respectively; RR 0.72; 95% CI, 0.63-0.82; P<0.0001). This provides further evidence of the significant benefit observed in the top line results reported late last year, and arguably provides a greater understanding of the magnitude of benefit.

1. Bhatt DL, et al. J Am Coll Cardiol 2019;Mar 18. Epub ahead of print.
2. Bhatt DL, et al. N Engl J Med 2019;380:11-22.

 



Posted on 6 June 201927 March 2024