Vascepa Trial (Omega 3 Fatty acids) - EVAPORATE

Vascepa Trial (EVAPORATE Trial) along with the three other major trials have proved the efficacy of omega-3 fatty acids in the reduction of cardiovascular mortality. Vascepa is a high dose of omega 3 fatty acids containing 4000 mg of Eicosapentaenoic acid (EPA).
In contrast to the commonly available over the counter omega 3 fatty acids formulations that contain DHA and Eicosapentaenoic acid, Vascepa is a highly purified form of Eicosapentaenoic acid.
DHA increases LDL levels while Eicosapentaenoic acid does not affect the LDL levels.

Why Lower triglyceride levels:

Despite the use of statins and other therapies, the rates of cardiovascular events remain high. In such patients, elevated triglycerides have been blamed for high mortality and cardiovascular events. However, Niacin, fibrates, and gemfibrozil have not shown to reduce cardiovascular risks despite optimal medical therapy. So, let's discuss the three important clinical trials before we start prescribing omega 3 fatty acids.

The JELIS trial:

One study in Japan (the JELIS trial) evaluated more than 18600 patients to receive either a statin or a statin plus 1.8 gms of Eicosapentaenoic acid (Omega 3 fatty acid - fish oil) daily. The study concluded that the risk of major cardiovascular events was reduced by 19% in patients receiving Eicosapentaenoic acid plus a statin. The JELIS trial along with the presumed anti-inflammatory, antioxidative, plaque-stabilizing, and membrane-stabilizing properties of omega 3 fatty acids encouraged to carry out the REDUCE-IT trial.

Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT):

It was a randomized double-blind, placebo-controlled trial that compared icosapent ethyl at a dose of 2 gm two times a day with a placebo that contained mineral oil to mimic the color and consistency of icosapent ethyl.
Patients who were enrolled in the study:
  • were equal to or older than 45 years of age and had established cardiovascular disease or
  • were 50 years of age or older and had diabetes mellitus plus at least one additional risk factor.
  • had a fasting triglyceride level of 150 - 499 mg per deciliter (1.69 to 5.63 mmol per liter) and
  • a low-density lipoprotein (LDL) cholesterol level of 41 - 100 mg per deciliter (1.06 to 2.59 mmol per liter) and
  • had been receiving a stable dose of a statin for at least 4 weeks.
Patients were excluded if:
  • they had severe heart failure,
  • active severe liver disease,
  • a glycated hemoglobin level greater than 10.0%,
  • a planned coronary intervention or surgery,
  • a history of acute or chronic pancreatitis, or
  • known hypersensitivity to the drug, placebo, fish, or shellfish.
The primary efficacy endpoints were a composite of:
  • cardiovascular death,
  • nonfatal myocardial infarction (including silent myocardial infarction),
  • nonfatal stroke,
  • coronary revascularization, or
  • unstable angina in a time-to-event analysis.
Among the 8179 patients who were enrolled, 70.7% were enrolled on the basis of secondary prevention and 29.3% on the basis of primary prevention. The patients were followed for about 5 years. After one year, a reduction in the triglyceride levels was seen in 18.3% in the icosapent ethyl group and an increase of 2.2% in the placebo group. 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. The risk of the primary (and secondary) composite endpoint of:
  • cardiovascular death,
  • nonfatal myocardial infarction,
  • nonfatal stroke,
  • coronary revascularization, or
  • unstable angina,
was significantly (25%) lower among the patients who received 2 g of icosapent ethyl two times a day than among those who received a placebo. In conclusion, the risk of major ischemic cardiovascular events was significantly lower with 2 g of icosapent ethyl two times a day than with placebo among patients with elevated triglyceride levels who were already receiving statin therapy,


Effect of Vascepa on Improving Coronary Atherosclerosis in People With High Triglycerides Taking Statin Therapy Trial:

Icosapent ethyl (Vascepa; Amarin Pharma Inc., Bedminster, NJ) is a prescription drug used as an adjunct to diet for the reduction of triglyceride levels in adults with triglyceride levels of 500 mg/dl or more. The EVAPORATE Vascepa trial is an ongoing trial that is evaluating the effects of icosapent ethyl 4 g/d on low‐attenuation plaque volume via multidetector computed tomography angiography (MDCTA) in a North American population of statin‐treated patients with elevated triglyceride levels (200–499 mg/dl). It is a randomized, double‐blind, placebo‐controlled trial.
The key inclusion and exclusion criteria of the EVAPORATE (Vacepa trial) are:
Inclusion Criteria
Exclusion Criteria
Age 30–85 y Use of dietary supplements or medications that may alter plasma lipids
Elevated TG (200–499 mg/dL) BMI > 40 kg/m2
LDL‐C ≥40 and ≤115 mg/dL on statin therapy History of known MI, stroke, life-threatening arrhythmia, or HF
Stable diet and exercise Pregnancy
Stable treatment with a statin ± ezetimibe Known genetic mutations/ polymorphisms that affect plasma lipids
Patients with narrowing of ≥20% in 1 coronary artery by invasive angiography or MDCTA
Written informed consent

The primary endpoint of the Vascepa trial (EVAPORATE) is the rate of change in low‐attenuation plaque volume (defined as −50 to 50 Hounsfield units [HU]

Secondary endpoints of the Vascepa trial (EVAPORATE) include:
Incident plaque rates quantitative changes in different plaque types and morphology
Changes in markers of inflammation including Lp‐PLA2 and hsCRP
Changes in lipids and lipoproteins including a standard lipid panel, lipoproteins, remnants, Apo‐A1/remnant ratio, EPA, AA, and EPA/AA ratio
Relationship between noncalcified coronary plaque burden and changes in the above and/or plaque‐vulnerability features

Principal Findings of the Vascepa trial (EVPORATE) to date:

The primary outcome (the percentage change in low attenuation plaque volume, for icosapent ethyl vs. placebo), was: 94% vs. 74% (p = 0.47). Secondary outcomes for icosapent ethyl vs. placebo:
  • Change in fibrofatty plaque volume: 25% vs. 87% (p = 0.65)
  • Change in total plaque volume: 26% vs. 15% (p = 0.0004)
Although the primary outcome has not been achieved, the change in total plaque volume has significantly reduced with its use.

Vascepa Trial and other omega 3 fatty acids trials Summary:

Omega 3 fatty acids, Eicosapentaenoic acid, in particular, are gaining importance again after the three trials (JELIS, REDUCE-IT, and the EVAPORATE). The JELIS trial set the ground, the REDUCE-IT trial followed it showing a reduction in cardiovascular mortality by 25%. The EVAPORATE trial is an ongoing trial to see the effect of VASCEPA (Eicosapentaenoic acid) on plaque regression. To date, the results of the study after 9 months of Eicosapentaenoic acid are promising. However, the results of the Vascepa after a total of 18 months are yet to be declared.