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Published on: February 26, 2013
Cardiovascular Benefits of Icosapent Ethyl in Patients With and Without Atrial Fibrillation in REDUCE-IT
Brian Olshansky1, Deepak L Bhatt2, Michael Miller3
1Department of Medicine University of Iowa Iowa City IA USA.
Insights
Icosapent ethyl (IPE) reduced cardiovascular events but increased atrial fibrillation (AF) hospitalizations. Patients with prior AF experienced higher AF rates with IPE, yet still benefited from consistent risk reductions in major cardiovascular events.
Area of Science:
- Cardiology
- Clinical Trials
- Pharmacology
Background:
- The REDUCE-IT trial demonstrated icosapent ethyl's (IPE) efficacy in reducing cardiovascular events.
- However, IPE was associated with an increased risk of atrial fibrillation/atrial flutter (AF) hospitalization.
Purpose of the Study:
- To conduct post hoc analyses of the REDUCE-IT trial.
- To assess the efficacy and safety of IPE versus placebo in patients with and without prior AF.
- To evaluate the relationship between IPE, prior AF, in-study AF, and cardiovascular outcomes.
Main Methods:
- Post hoc analysis of REDUCE-IT trial data.
- Stratification of patients based on prior AF status and in-study AF hospitalization.
- Assessment of cardiovascular composite endpoints, stroke, and serious bleeding events.
Main Results:
- In-study AF hospitalization rates were significantly higher in patients with prior AF, particularly those randomized to IPE.
- Serious bleeding rates trended higher with IPE but were not significantly different based on prior AF or in-study AF hospitalization.
- Patients with prior AF demonstrated similar relative risk reductions for primary and key secondary composite endpoints with IPE compared to placebo.
Conclusions:
- Prior AF is associated with higher in-study AF hospitalization rates, especially with IPE treatment.
- IPE provides consistent cardiovascular risk reduction benefits across primary, key secondary, and stroke endpoints, irrespective of prior AF status or in-study AF hospitalization.
- While serious bleeding trended higher with IPE, this was not influenced by prior AF or subsequent AF events.
Abstract:
Background In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), icosapent ethyl (IPE) versus placebo) reduced cardiovascular death, myocardial infarction, stroke, coronary revascularization, or unstable angina requiring hospitalization, but was associated with increased atrial fibrillation/atrial flutter (AF) hospitalization (3.1% IPE versus 2.1% placebo; P=0.004). Methods and Results We performed post hoc efficacy and safety analyses of patients with or without prior AF (before randomization) and with or without in-study time-varying AF hospitalization to assess relationships of IPE (versus placebo) and outcomes. In-study AF hospitalization event rates were higher in patients with prior AF (12.5% versus 6.3%, IPE versus placebo; P=0.007) versus without prior AF (2.2% versus 1.6%, IPE versus placebo; P=0.09). Serious bleeding rates trended higher in patients with (7.3% versus 6.0%, IPE versus placebo; P=0.59) versus without prior AF (2.3% versus 1.7%, IPE versus placebo; P=0.08). With IPE, serious bleeding trended higher regardless of prior AF (interaction P value [Pint]=0.61) or postrandomization AF hospitalization (Pint=0.66). Patients with prior AF (n=751, 9.2%) versus without prior AF (n=7428, 90.8%) had similar relative risk reductions of the primary composite and key secondary composite end points with IPE versus placebo (Pint=0.37 and Pint=0.55, respectively). Conclusions In REDUCE-IT, in-study AF hospitalization rates were higher in patients with prior AF especially in those randomized to IPE. Although serious bleeding trended higher in those randomized to IPE versus placebo over the course of the study, serious bleeding was not different regardless of prior AF or in-study AF hospitalization. Patients with prior AF or in-study AF hospitalization had consistent relative risk reductions across primary, key secondary, and stroke end points with IPE. Registration URL: https://clinicaltrials.gov/ct2/show/NCT01492361; Unique Identifier: NCT01492361.
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