Icosapent Ethyl Benefits Regardless of Baseline LDL-c
Icosapent Ethyl Benefits Regardless of Baseline LDL-c
Source: Journal of the American Heart Association. 2025 (Published).
Key Points:
1. Study Background:
• The REDUCE-IT trial previously showed that icosapent ethyl reduces cardiovascular (CV) events in high-risk patients(i.e., those with established vascular disease or its equivalents) with elevated triglycerides and LDL-c ≤100 mg/dL who are on statins.
• This secondary analysis explored whether baseline LDL-c level (<55 mg/dL vs. ≥55 mg/dL) impacts the treatment’s benefit.
2. Study Population and Design:
• 8179 patients with high CV risk, triglycerides 135–499 mg/dL, and LDL-c 41–100 mg/dL.
• Randomized to icosapent ethyl 2 g BID vs. placebo.
• 1058 patients (12.9%) had LDL-c <55 mg/dL, 7117 (87.1%) had LDL-c ≥55 mg/dL.
3. Primary Outcome:
• Composite of CV death, nonfatal MI, stroke, revascularization, or unstable angina.
• Icosapent ethyl reduced risk in both LDL-c subgroups:
• LDL-c <55 mg/dL: HR 0.66; ARR: 6.6%; NNT: 15; P=0.003
• LDL-c ≥55 mg/dL: HR 0.76; ARR: 4.5%; NNT: 22; P<0.0001
• No interaction by LDL-c level (P=0.40), suggesting consistent benefit.
4. Secondary Outcome (CV death, MI, or stroke):
• LDL-c <55 mg/dL: HR 0.55; ARR: 6.4%; NNT: 16; P=0.0007
• LDL-c ≥55 mg/dL: HR 0.76; ARR: 3.2%; NNT: 32; P<0.0001
• Again, no significant interaction (P=0.11).
5. Safety Findings:
• Similar rates of serious adverse events (19.7% vs. 20.0%) and drug-related adverse events (12.6% vs. 12.2%) between groups.
• Slightly higher atrial fibrillation/flutter with icosapent ethyl (5.8% vs. 4.5%; P=0.008).
• Trend toward increased serious bleeding (2.7% vs. 2.1%; P=0.06).
• No significant differences by LDL-c levels.
6. Conclusion: the study supports the following clinical principle: “Treat elevated hypertriglyceridemia in high-risk patients regardless of baseline LDL-c levels.
• Icosapent ethyl significantly reduces CV events in statin-treated patients at high CV risk with elevated triglycerides, regardless of baseline LDL-c levels.
• Patients with optimal LDL-c (<55 mg/dL) still benefit substantially.
