Cardiovascular Benefits of Icosapent Ethyl in Patients With and Without Atrial Fibrillation in REDUCE-IT.
Level 2 - randomized trial
Post hoc subgroup analysis of an individual randomized controlled trial
PubMed 36802845 · doi:10.1161/JAHA.121.026756
What was done
Post hoc efficacy and safety subgroup analysis of the REDUCE-IT randomized controlled trial evaluating icosapent ethyl (IPE) versus placebo in patients with prior atrial fibrillation/flutter (AF, n = 751) and without prior AF (n = 7,428), as well as by in-study time-varying AF hospitalization.
What was found
In-study AF hospitalization was higher with IPE than placebo, especially in patients with prior AF (12.5% vs 6.3%, P = 0.007) compared to those without prior AF (2.2% vs 1.6%, P = 0.09). Serious bleeding rates trended higher in patients with prior AF (7.3% vs 6.0%, P = 0.59) versus without (2.3% vs 1.7%, P = 0.08), with no significant interaction between IPE and prior AF (interaction P = 0.61) or postrandomization AF hospitalization (interaction P = 0.66). Relative risk reductions for primary and key secondary composite cardiovascular endpoints with IPE were similar between patients with and without prior AF (interaction P = 0.37 and interaction P = 0.55, respectively).
Why it matters
Although icosapent ethyl increases the risk of AF hospitalization—particularly in patients with prior AF—its cardiovascular benefits remain consistent irrespective of AF history or in-study AF events.
Limits
This is a post hoc subgroup analysis, which increases the risk of type I error. The abstract does not report point estimates, hazard ratios, or absolute event rates for the primary composite, key secondary, or stroke endpoints. Only 9.2% of the trial population had preexisting AF at baseline.
Cited by
- supports Both the REDUCE-IT and STRENGTH clinical trials demonstrated a small but statistically significant increase in atrial fibrillation.
- supports Despite the observed increase in atrial fibrillation with high-dose omega-3, there is no increased risk for stroke, and instead there is a decreased risk for stroke.