Icosapent ethyl may REDUCE ischaemic stroke risk

Icosapent ethyl may reduce the risk of ischaemic stroke in statin-treated patients who have or are at risk of atherosclerosis, according to post hoc findings of the REDUCE-IT* trial presented at ISC 2021.

“Icosapent ethyl is a new way to further reduce the risk of stroke in patients with atherosclerosis or who are at high risk of stroke, who have elevated triglyceride levels and are already taking statins,” said lead author Professor Deepak Bhatt from the Brigham and Women’s Hospital Heart & Vascular Center and Harvard Medical School in Boston, Massachusetts, US.

Participants in this multinational, double-blind trial were 8,179 individuals with controlled low-density lipoprotein cholesterol (1.06–2.59 mmol/L) and elevated triglycerides (1.52–5.63 mmol/L [fasting]) who had or were at risk for atherosclerosis and were being treated with statins. They were randomized to receive icosapent ethyl (4 g/day) or placebo.

A significant 28 percent reduction in the time to first fatal or nonfatal stroke was noted with icosapent ethyl vs placebo (2.4 percent vs 3.3 percent; hazard ratio [HR], 0.72, 95 percent confidence interval [CI], 0.55–0.93; p=0.01), with an absolute risk reduction of 0.9 percent, and number needed to treat of 114. [ISC 2021, presentation 57]

Approximately 14 fatal or nonfatal strokes were prevented for every 1,000 patients treated with icosapent ethyl for 5 years (rate ratio, 0.68, 95 percent CI, 0.52–0.91; p=0.008). 

This significant reduced risk of first stroke with icosapent ethyl vs placebo was evident for ischaemic stroke (2.0 percent vs 3.0 percent; HR, 0.64, 95 percent CI, 0.49–0.85; p=0.002).

The incidence of haemorrhagic strokes was low and did not significantly differ between the icosapent ethyl and placebo groups (0.3 percent vs 0.2 percent; p=0.55).

These findings add to the previously published primary outcome results of the REDUCE-IT trial which showed a 25 percent reduced risk of a composite of cardiovascular (CV) death, nonfatal myocardial infarction (MI), nonfatal stroke, coronary revascularization, or unstable angina with icosapent ethyl vs placebo after a median follow-up of 4.9 years (17.2 percent vs 22.0 percent; HR, 0.75, 95 percent CI, 0.68–0.83; p<0.001). [N Engl J Med 2019;380:11-22]

This analysis also demonstrated a 26 percent reduced risk of the secondary outcome – a composite of CV death, nonfatal MI, or nonfatal stroke – with icosapent ethyl vs placebo (11.2 percent vs 14.8 percent; HR, 0.74, 95 percent CI, 0.65–0.83; p<0.001).

Bhatt and co-authors pointed out that the icosapent ethyl formulation used in REDUCE-IT is a highly purified form of the stable ethyl ester of eicosapentaenoic acid. “It is very different in terms of purity compared to omega-3 fatty acid supplements available over-the-counter, and these results do not apply to supplements,” Bhatt stressed. He also cautioned that icosapent ethyl may increase the risk of minor bleeding.

“Physicians need to be aware that this agent has efficacy for primary stroke prevention,” said Professor Karen Furie, volunteer expert from the American Stroke Association who was not affiliated with the trial.

“It should be considered in patients who are on a statin and have been counselled on the importance of lifestyle modifications but continue to have elevated levels of triglycerides. It should be one of the considerations in any patient who’s at high risk for stroke,” she added.