We spoke with Robert Busch, MD, an endocrinologist at Albany Medical Center about the REDUCE-IT cardiovascular risk reduction clinical trial in which 40 of his patients participated. This large, multi-year trial was the first to show a meaningful reduction in cardiovascular risk — 25% reduction compared to placebo.

Vascepa® is Amarin’s brand name for icosapent ethyl, a prescription form of eicosapentaenoic acid ethyl ester (EPA) isolated from all other components of fish oil.  Vascepa is already approved by the FDA for treatment of people with very high triglycerides, The REDUCE-IT trial was sponsored by Amarin to determine if additional indications were appropriate for icosapent ethyl.

Other cardiovascular risk studies failed to show meaningful results while the REDUCE-IT study clearly demonstrated risk reduction.  I now have hundreds of my diabetes patients using Vascepa, said Robert Busch, MD

Background

The connection between cardiovascular disease (CVD) and type 2 diabetes (T2D) has long been established, with CVD being the #1 cause of death in people with diabetes globally. More than a third of U.S. adults with diabetes, or approximately 10 million people, have high triglycerides and are at elevated risk for CVD.

The new cholesterol guidelines from the American College of Cardiology and American Heart Association advise that people aged 40 to 75 with diabetes, be on “moderate-intensity” statin therapy. Yet a recent analysis found that despite statin use, high triglycerides and diabetes were significant predictors of worse cardiovascular and health economic outcomes.

The Japanese study JELIS, published in 2007, showed that adding 1.8 grams per day of EPA to the fish-rich Japanese diet meaningfully reduced cardiovascular risk. The REDUCE-IT study tested at higher doses —  4 grams per day — of EPA on people in the US and Europe who do not consume fish at the same levels of Japanese.

Cardiovascular Risk Studies

Positive Results: REDUCE-IT

Background

Patients with elevated triglyceride levels are at increased risk for ischemic events. Icosapent ethyl, an isolated form of the omega-3 eicosapentaenoic acid, lowers triglyceride levels, but data are needed to determine its effects on ischemic events.

Results

A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary end-point event occurred in 17.2% of the patients in the icosapent ethyl group, as compared with 22.0% of the patients in the placebo group (hazard ratio, 0.75; 95% confidence interval).

Key Findings

• Cardiovascular Death Reduced by 20%
• Fatal or Nonfatal Heart Attacks Reduced by 31% 
• Fatal or Nonfatal Stroke Reduced by 28%
• Urgent or Emergent Coronary Revascularization Reduced by 35%
• Hospitalization for Unstable Angina Reduced by 32%

Conclusions

Among patients with elevated triglyceride levels despite the use of statins, the risk of ischemic events, including cardiovascular death, was significantly lower among those who received 2 g of icosapent ethyl twice daily than among those who received placebo.  The potential mechanisms behind this reduction in risk are discussed in the New England Journal paper by Bhatt, et al. and include TG reduction, anti-thrombotic effects, antiplatelet or anticoagulant effects, membrane-stabilizing effects, effects on stabilization and/regression of coronary plaque and inflammation reduction.  

Resources

• See study published in New England Journal of Medicine
• Amarin Infographic of results

Disappointing Results: VITAL — Vitamin D3 or omega-3 fatty acids

Background

VITAL is an ongoing research study in 25,871 men and women across the U.S. investigating whether taking daily dietary supplements of vitamin D3 (2000 IU) or omega-3 fatty acids (called Lovaza® in the US and Omacor® in the EU) fish oil, 1 gram reduces the risk for developing cancer, heart disease, and stroke in people who do not have a prior history of these illnesses.

Key Findings

Vitamin D supplementation

• Did not reduce the risk of cancer
• Did not reduce the risk of major cardiovascular events (heart attack, stroke, or cardiovascular death considered together)
• Appeared to reduce the risk of cancer-related death

Omega-3 fatty acid supplementation

• Did not reduce the risk of cancer
• Did not reduce the risk of major cardiovascular events in the overall study population, but did reduce the risk of these events by 19% in people with low fish intake
• Reduced risk of heart attack by 28%, when a heart attack was considered separately from other cardiovascular events; the benefit appeared strongest in African Americans

Disappointing Results: ORIGIN — Sufficient Basal Insulin may Reduce Cardiovascular Events

Background

The study involved 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes. Participants received insulin glargine or standard care plus n–3 fatty acids or placebo with the use of a 2-by-2 factorial design.

The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups.

Conclusions

When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers.

Disappointing Results: ASCEND — Aspirin for Primary Prevention in Persons with Diabetes Mellitus

Background

Diabetes mellitus is associated with an increased risk of cardiovascular events. Aspirin use reduces the risk of occlusive vascular events but increases the risk of bleeding; the balance of benefits and hazards for the prevention of first cardiovascular events in patients with diabetes is unclear.

Conclusions

Aspirin use prevented serious vascular events in persons who had diabetes and no evident cardiovascular disease at trial entry, but it also caused major bleeding events. The absolute benefits were largely counterbalanced by the bleeding hazard.