REDUCE-IT (secondary analysis, high 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
29.0% female
71.0% male
N = 7117
7117 patients (2091 female, 5026 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=3537 icosapent ethyl (at a dose of 2 g BID).
N=3580 placebo (matching placebo BID).
Primary outcome
CV death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina
17.4%
21.9%
21.9 %
16.4 %
10.9 %
5.5 %
0.0 %
Icosapent
ethyl
Placebo
Significant
decrease ▼
NNT = 22
Significant decrease in CV death, nonfatal MI, nonfatal stroke, coronary revascularization, or unstable angina (17.4% vs. 21.9%; HR 0.76, 95% CI 0.69 to 0.85).
Secondary outcomes
Significant decrease in CV death, nonfatal MI, or nonfatal stroke (11.5% vs. 14.7%; HR 0.76, 95% CI 0.67 to 0.87).
Significant decrease in CV death or nonfatal MI (9.8% vs. 12.3%; HR 0.78, 95% CI 0.68 to 0.9).
No significant difference in CV death (4.4% vs. 5.1%; HR 0.85, 95% CI 0.69 to 1.06).
Safety outcomes
No significant difference in severe and drug-related treatment-emergent adverse events.
Significant differences in AF/flutter (5.6% vs. 4.4%), any bleeding treatment-emergent adverse event or hemorrhagic stroke (11.9% vs. 9.9%).
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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