REDUCE-IT PAD: Icosapent Ethyl Provides Consistent Benefit in PAD Patients

Conference | <b>American Heart Association</b>

Deepak Bhatt, MD, MPH, provides perspective on the results of the REDUCE-IT PAD analysis he presented at the American Heart Association 2021 Scientific Sessions.

New research from the American Heart Association (AHA) 2021 Scientific Sessions is providing insight into the effects of icosapent ethyl (Vascepa) on cardiovascular outcomes based on whether or not a patient had a diagnosis of peripheral artery disease (PAD).

After a contentious AHA 2020 that saw some leverage the results of STRENGTH to hurl criticisms toward REDUCE-IT and the effects of icosapent ethyl, the latest REDUCE-IT analysis presented at AHA 2021 build on the results of previous analyses and suggest patients with PAD using the EPA-based agent lowered their risk of suffering a primary outcome event by 22% compared to placebo therapy.

"With this analysis, we see icosapent ethyl reduced total end points in terms of MACE by 32% and, again, this is consistent with the overall trial findings but does provide, I believe, a new option for patients with PAD that did not exist before," said Deepak Bhatt, MD, MPH, executive director of interventional cardiovascular programs at Brigham and Women’s Hospital, in an interview with Practical Cardiology.

An 8179-patient trial comparing icosapent ethyl against placebo therapy in statin-treated patients aged 45 years and older with elevated triglycerides, the trial, which was originally presented at AHA 2018 and published in the New England Journal of Medicine, was designed with a primary composite cardiovascular end point that included time to cardiovascular death, myocardial infarction (MI), stroke, coronary revascularization, or hospitalization for unstable angina. With a median follow-up of 4.9 years, results indicated use of icosapent ethyl was associated with a 25% reduction in risk of the primary end point.

Since these results were published, numerous REDUCE-IT analyses assessing the effects of icosapent ethyl in subgroups, including based on diagnosis of diabetes and increased BMI. The REDUCE-IT PAD analysis examined the effects of icosapent ethyl among the subgroup of patients with PAD. Of the 5785 REDUCE-IT patients with a history of cardiovascular disease at baseline, 688 had a diagnosis of PAD.

Upon analysis, results indicated use of icosapent ethyl provided a statistically similar risk reduction for first (P=.58) and total (P=.78) primary end point events in those with established cardiovascular disease with or without PAD. Among patients with PAD, the primary end point event rate was 26.2% with icosapent ethyl and 32.8% with placebo therapy (HR, 0.78 [95% CI, 0.59-1.03]; P=.08). For total events, the event rates among those using icosapent ethyl was 112.8 per 1000 patient-years with icosapent ethyl and 162.3 per 1000 patient-years with placebo therapy (RR, 0.68 [95% CI, 0.48-0.95]; P=.03).

Analyses assessing absolute risk reductions and NNT indicate icosapent ethyl provided benefit for patients with and without PAD. Additionally, results of safety analyses did not differ substantially based on PAD history and was generally consistent with the overall REDUCE-IT trial.

For more insight into how the results of the latest REDUCE-IT analysis add to our understanding of the agent, Practical Cardiology reached out to Bhatt and that conversation is the subject of the following AHA 2021 House Call.

This study, “Benefits of Icosapent Ethyl in Patients with Prior Peripheral Artery Disease: REDUCE-IT PAD,” were presented at AHA 2021.