REDUCE-IT

Clinical Trial Details

Evaluation of the Effect of AMR101 on Cardiovascular Health and Mortality in Hypertriglyceridemic Patients With Cardiovascular Disease or at High Risk for Cardiovascular Disease: REDUCE-IT (Reduction of Cardiovascular Events With EPA - Intervention Trial)

The purpose of this study is To evaluate whether icosapent ethyl + statin is superior to statin therapy alone to prevent/reduce long-term CV events in high-risk mixed dyslipidemia patients.

Key Findings

High-dose icosapent ethyl vs. placebo in at-risk patients significantly reduced the composite CVD endpoint: risk of CV death, MI, stroke, coronary revascularization, and unstable angina.

Principal Investigator Deepak Bhatt on REDUCE-IT

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Deepak Bhatt, MD, MPH, discussed the REDUCE-IT results after presenting the trial at #AHA18, the Scientific Sessions 2018 meeting in Chicago, Illinois.

REDUCE-IT Commentary

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Don Lloyd-Jones, MD, ScM, vice chair of the program committee for Scientific Sessions 2018, comments on the results of the REDUCE-IT trial and what further study may come of this trial.

Purpose: to evaluate whether high-dose icosapent ethyl lowers ischemic event rates beyond statin therapy in at-risk patients

Trial Design: Phase 3b, randomized, double-blinded, placebo-controlled; median follow-up 4.5 years; . >8000 patients on statin therapy treated with icosapent ethyl 4g/day or placebo; fasting triglycerides ≥150 mg/dL and <500 mg/dL; LDL-C >40 mg/dL and ≤100 mg/dL; prior CV event or other risk factors.

Primary Endpoints: composite CVD endpoint: CV death, MI, stroke, coronary revascularization, unstable angina.

Secondary Endpoints: composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke

REDUCE-IT Trial Data
Prespecified Hierarchical
Testing Results
isocapent euthyl placebo  
Composite Primary Endpoint 17.2% 22.0% 25% reduction
HR=0.75
P<0.001
Composite Secondary Endpoint 11.2% 14.8% HR=0.74
P<0.001
Coronary Revascularization 5.3% 7.8% HR=0.65
p<0.001
MI - fatal or non-fatal 6.1% 8.7% 31% reduction
HR=0.69 p=0.01
Stroke - fatal or non-fatal 2.4% 3.3% 28% reduction
HR=0.72 p=0.01
CV Death 4.3% 5.2% 20% reduction
HR=0.80 p=0.30
Total Mortality 6.7% 7.6% 13% reduction
HR=0.87 p=0.09

Results: High-dose icosapent ethyl vs. placebo in at-risk patients significantly reduced the composite CVD endpoint: risk of CV death, non-fatal MI, stroke, coronary revascularization, and unstable angina needing hospitalization.

Detailed Results

Primary endpoint: Prespecified Hierarchical Testing

  1. MACE Composite:
    Icosapent Ethyl: 17.2%; placebo: 22.0%; HR=0.75; p<0.001
     
  2. Secondary endpoints: Prespecified Hierarchical Testing
    • Secondary composite: Icosapent Ethyl: 11.2 %; placebo: 14.8%; HR=0.75; p<0.001
       
    • Coronary revascularization:
      Icosapent Ethyl: 5.3 %; placebo: 7.8%; HR=0.65; p<0.001
       
    • CV death:
      Icosapent Ethyl: 4.3 %; placebo: 5.2%; HR=0.80; p<0.03
  • Secondary Endpoints, cont.
    • Fatal or non-fatal stroke : Icosapent Ethyl: 2.4 %; placebo: 3.3%; HR=0.72; p<0.01
       
    • Hospitalization for unstable angina: Icosapent Ethyl:2.6%; placebo3.8%; HR=0.68; p=0.002
       
    • Total mortality, non-fatal MI or stroke:
      Icosapent Ethyl: 13.4 %; placebo: 16.9%; HR=0.77; p<0.001
       
    • Total mortality:
      Icosapent Ethyl: 6.7 %; placebo: 7.6%; HR=0.87; p=0.09

Background

Trial Design — median 4.5-year follow-up. Phase 3b double-blinded, parallel, placebo-controlled, randomized trial of icosapent ethyl vs placebo.

Trial Population — Phase 3; 8179 patients 45 years and older on stable statin therapy with:

  1. fasting triglycerides ≥150 mg/dL and <500 mg/dL and
  2. LDL-C >40 mg/dL and ≤100 mg/dL and
  3. a prior cardiovascular event or diabetes and other cardiovascular risk factors

Primary Endpoint

  • Composite of CV death, non-fatal MI or stroke, coronary revascularization, and hospitalization for unstable angina.

Secondary Endpoints

  • Composite of cardiovascular death, non-fatal myocardial infarction or stroke
  • Non-fatal MI
  • Coronary revascularization
  • CV death
  • Fatal or non-fatal stroke
  • Total mortality, non-fatal MI or stroke
  • Total mortality

Sponsor— Sponsor: Amarin Pharma Inc.

References

Key Words

Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Disease
Acute Coronary Syndrome
Cardiovascular Disease
Arteriosclerosis
Vascular Disease
Angina Pectoris
Chest Pain
Anticholesteremic Agents
Hypolipidemic Agents
Lipid Regulating Agents
hypertriglyceridemia
dyslipidemia
omega-3 fatty acids
statin
triglycerides
EPA
docosahexaenoic acid
fish
fatty acids
fibrates
niacin
lipids
lipoprotein
atorvastatin
simvastatin
lovastatin
Related Clinical Topics

atherosclerosis, drug discovery, cholesterol, stroke, heart failure, vascular health, diabetes, metabolic syndrome, prevention