REDUCE-IT (secondary analysis, optimal baseline LDL-C)
Trial question
What is the effect of icosapent ethyl in statin-treated patients with elevated triglycerides and high cardiovascular risk?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
25.0% female
75.0% male
N = 1058
1058 patients (265 female, 793 male).
Inclusion criteria: statin-treated patients with elevated triglycerides, high cardiovascular risk, and a baseline LDL-C < 55 mg/dL.
Key exclusion criteria: severe HF; life-threatening disease other than CVD; active severe liver disease; HbA1c > 10%; poorly controlled hypertension; planned coronary intervention or any non-cardiac major surgical procedure; history of acute or chronic pancreatitis.
Interventions
N=549 icosapent ethyl (at a dose of 2 g BID).
N=509 placebo (matching placebo BID).
Primary outcome
CV death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina
16.2%
22.8%
22.8 %
17.1 %
11.4 %
5.7 %
0.0 %
Icosapent
ethyl
Placebo
Significant
decrease ▼
NNT = 15
Significant decrease in CV death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina (16.2% vs. 22.8%; HR 0.66, 95% CI 0.5 to 0.87).
Secondary outcomes
Significant decrease in CV death, nonfatal MI, or nonfatal stroke (9.5% vs. 15.9%; HR 0.55, 95% CI 0.39 to 0.78).
Significant decrease in CV death or nonfatal MI (8.2% vs. 13.4%; HR 0.57, 95% CI 0.39 to 0.83).
Significant decrease in CV death (3.3% vs. 5.9%; HR 0.52, 95% CI 0.29 to 0.94).
Safety outcomes
No significant differences in severe and drug-related treatment-emergent adverse events, AF/flutter, any bleeding treatment-emergent adverse event or hemorrhagic stroke.
Significant difference in serious treatment-emergent adverse event leading to withdrawal of study drug (1.5% vs. 3.9%).
Conclusion
In statin-treated patients with elevated triglycerides, high cardiovascular risk, and a baseline LDL-C < 55 mg/dL, icosapent ethyl was superior to placebo with respect to CV death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina.
Reference
Rahul Aggarwal, Deepak L Bhatt, Ph Gabriel Steg et al. Cardiovascular Outcomes With Icosapent Ethyl by Baseline Low-Density Lipoprotein Cholesterol: A Secondary Analysis of the REDUCE-IT Randomized Trial. J Am Heart Assoc. 2025 Mar 4;14(5):e038656.
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