This is a story of two medications, with the unwritten last chapter likely to influence the global sales of a multibillion-dollar drug. With money at stake, it involves academics warring on both sides, possible conflicts of interests, and the diametrically opposed results of two expensive research studies, funded by two different pharmaceutical companies.

In the background is a decade-old argument: Does fish oil reduce the risk of having a heart attack?

It begins with a study published in the New England Journal of Medicine called REDUCE-IT, involving a prescription drug called Icosapent ethyl (Vascepa). The trial showed a 25% decrease in heart attack risk, which led to the drug’s approval by the FDA. It quickly has become widely used, well-advertised, and is costly.

A quick lesson on fish oil: It contains two omega-3 fatty acids called docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).

Vascepa is a purified form of fish oil, entirely composed of EPA, and proponents of this study believe that it is the pure EPA that is responsible for the results. The main investigator of REDUCE-IT, Deepak Bhatt, a cardiologist at Brigham and Women’s Hospital in Boston, points out that research has shown that pure EPA stabilizes cell membranes, and that DHA can actually raise LDL cholesterol levels, helping to explain why it works. His conflicts of interest include taking money from many pharma companies, including the company that funded this study.

A second study recently published in JAMA, called the STRENGTH trial, compared a similar dose of the carboxylic form of omega 3 fatty acid, called Epanova, which combines DHA and EPA. Both trials looked at a similar group of patients who all took a statin, with a mixture of coronary risk factors and known coronary artery disease, but had dramatically different results. The STRENGTH trial showed no benefit in cardiac outcome at all.

Then the academic battle began. Steven Nissen, a cardiologist at the Cleveland Clinic, chair of STRENGTH’s executive committee and a man with many conflicts of interest of his own, argued that the difference between the studies was because they used a different placebo. In most studies, the drug being tested is compared directly to a placebo. In the STRENGTH trial, this placebo was corn oil, which is inert. In the REDUCE-IT trial, the placebo was mineral oil, which Nissen argued is pro-inflammatory. In other words, it is possible that the mineral oil worsened heart disease in the placebo group, thus magnifying the beneficial effect of fish oil.

“I don’t think we can believe that fish oil is beneficial unless REDUCE-IT is repeated with a neutral control like corn oil,” Nissen said.

Whom to believe? If the beneficial effects of Vascepa are related to EPA and not because of an unfortunate choice of placebo, then Vascepa is a valuable medication and has a unique role in treating coronary artery disease. If Vascepa, as Nissen implies, is just another fish oil that may not prevent heart attacks, then it is not worth the extra cost.

Possible conflicts of interests play an important role. They are present on both sides and are ubiquitous in the field of cardiology. These conflicts are not just financial. Reputations and ego play a role.

Full disclosure: I was one of the multitude of co-investigators in the STRENGTH trial, did not receive any financial compensation, but found after four years of having my patients take either the drug or a placebo, that I could not help but root for a positive result, and was disappointed when it showed no benefit.

These trials are very expensive to run. Imagine spending hundreds of millions of dollars and getting a negative result like what happened in STRENGTH. When pharma companies gets a positive result like in REDUCE-IT, they want to recover their costs. That is one of the reasons Vascepa is so expensive. The company sponsoring STRENGTH will never recover its costs, as their drug doesn’t work and will not be prescribed.

The final chapter of this story of two different kinds of omega 3 fatty acids has not yet been written. Sadly, even if further information proves that the Vascepa effect is real, that will not solve the problem that many of my patients still cannot afford it.

In the meantime, I recommend patients still take Vascepa if they meet all of the following criteria: they have known coronary artery disease, are taking it with a statin, have high triglyceride levels, are tolerating it without side effects, and it is affordable under their health plan.

David Becker is a board-certified cardiologist with Chestnut Hill Temple Cardiology in Flourtown and a member of the Inquirer’s Health Advisory Panel.