In our efforts to protect people from cardiovascular events, we know that managing cholesterol is of key importance. Our primary focus is on the ‘bad’ cholesterol, called LDL. We know that another part of the cholesterol profile, called triglycerides, are also a marker of cardiovascular risk, but a treatment that successfully lowers triglycerides and reduces cardiovascular risk on top of good LDL lowering has evaded us – until now. A medication called icosapent ethyl has recently become available in Canada, which reduces triglycerides AND reduces cardiovascular events.
Icosapent ethyl (IPE), marketed under the trade name Vascepa, is a highly purified and stable EPA ester that is derived from fish oil. To dial down into what this is exactly, here’s a little backgrounder:
- Commercial fish oils are a combination of omega-3 fatty acids (good) and/or omega-6 fatty acids (bad).
- The omega-3 fatty acids are comprised of EPA and DHA.
- EPAs are the omega-3 fatty acids that are good for the lining of blood vessels, inhibiting lipid oxidation and preserving membrane structure.
- Common fish oil contains only about 21% EPA, whereas icosapent ethyl is 96% EPA ester that is chemically distinct from the EPA in commercial fish oil.
- Bonus! No fishy burps with icosapent ethyl. (this can happen with commercial fish oil)
Icosapent ethyl was approved in USA in 2012 for lowering of triglyceride levels, and was then studied to see if it could reduce cardiovascular events in the REDUCE-IT trial, published in the New England Journal of Medicine. The study enrolled 8,179 people age 45 or older who either had existing cardiovascular disease (71% of patients), or people age 50 or older who had diabetes and at least one additional risk factor for cardiovascular disease, but without known cardiovascular disease (29% of patients). Baseline triglyceride level had to be between 1.5-5.6 mmol/L to be included in the study, and all patients had to be on statin treatment (gold standard treatment for LDL lowering), with a baseline LDL between 1.06-2.59 mmol/L. The definition of cardiovascular events was a composite of: cardiovascular death, non fatal heart attack, non fatal stroke, coronary revascularization, and unstable angina.
After a median duration of 4.9 years, they found that icosapent ethyl decreased the risk of cardiovascular events by an impressive 25% compared to placebo. Cardiovascular death was reduced by 20%. Interestingly, the benefit was the same regardless of how high triglycerides were at the time of entry into the study, and also the same regardless of the triglyceride level achieved at 1 year into the study.
In terms of risks, there was a higher risk of atrial fibrillation or flutter (5.3% in the IPE group vs 3.9% in the placebo group). The reasons for this are not clear. Serious bleeding events occurred in 2.7% of the IPE group vs 2.1% of the placebo group, suggesting that part of the way this medication works may be an antithrombotic (anti-blood clotting) mechanism, but again this is not clear.
BOTTOM LINE: Icosapent ethyl markedly reduces the risk of cardiovascular events in people with known cardiovascular disease, and in people with diabetes with no known cardiovascular disease, on top of the gold standard statin treatment for reducing cholesterol-related risk. Based on the REDUCE-IT trial, treating just 21 people for 4.9 years will prevent one cardiovascular event. This benefit is seen irrespective of triglyceride levels in the range studied in the REDUCE-IT trial, suggesting that at least some of the benefit of this medication may be related to its metabolic effects other than a reduction in triglyceride levels. To be clear, this benefit has NOT been seen with commercial fish oils, and commercial fish oils are NOT a substitute for this prescription medication.
Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the makers of icosapent ethyl (HLS Therapeutics).
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