Without full data, Vascepa trial results still a little bit fishy

By Judith Garber | October 1, 2018

You may have heard the conventional wisdom that fish oil is healthy for the heart (or that it gives your hair more shine, as teen magazines used to tout). But does taking omega-3 fatty acid supplements help prevent cardiovascular events in patients at high risk of heart attack or stroke?

Fish oil and heart health

The theory linking these supplements to better cardiovascular outcomes has been challenged by recent evidence, including two studies published this year. A meta-analysis in JAMA Cardiology published in March looked at 10 trials of omega-3 fatty acid usage in patients with high cardiovascular risk, and found no significant reduction in heart attack, stroke, or coronary heart disease events. And a Cochrane review published in July looked at more than two dozen trials and found little or no effect of omega-3 supplements on cardiovascular mortality, cardiovascular events, stroke, or arrhythmia for patients at varying risk of cardiovascular events.

However, a new trial from drug company Amarin has reopened the conversation. The REDUCE-IT trial included more than 8,000 patients with high risk of cardiovascular events who were already taking statins. Patients were randomized to take Vascepa, a new prescription omega-3 supplement, or a placebo and followed for five years. Unlike over-the-counter fish oil supplements, Vascepa contains a purified version of just one omega-3 fatty acid and is prescribed at a higher dose than other supplements.

Patients taking Vascepa had a 25% relative reduction in the primary endpoint, a much greater outcome than expected. Unsurprisingly, share prices of Amarin’s stock more than tripled the day after the press release was published.

Unanswered questions

Does this study mean we should start prescribing omega-3 supplements for all cardiovascular patients? Not just yet, some doctors say. Amarin has only released their “topline results,” not the detailed data, so there are still critical pieces of information we don’t know about the trial and its results. For example, as Andrew Holtz, MPH, Kathleen Fairfield, MD, DrPH, and Kevin Lomangino write in Health News Review, a 25% decrease in cardiovascular events does not give any information on the absolute reduction in negative outcomes.

Further, the primary endpoint of the study was a composite of 5 outcomes: cardiovascular death, non-fatal heart attack, non-fatal stroke, coronary revascularization, or unstable angina requiring hospitalization. However, the topline results provided by Amarin don’t distinguish between how much of the 25% reduction is from reductions in death or hospitalization for chest pain. If all of the 25% is reduced mortality, that’s a gamechanger; but it it’s mostly or all from unstable angina (a measurement that is susceptible to bias), that’s less impressive. We won’t know until we get the full data next month.

Are topline reports necessary?

Amarin’s press release has generated a lot of hype, and some doctors are already gearing up to prescribe Vascepa for their patients with cardiovascular disease. “These [REDUCE-IT] results will definitely change my practice and the way I treat patients,” said cardiologist Dr. Norman Lepor, quoted in STAT.

Other doctors have questioned the appropriateness of early press releases like this one. As Dr. John Mandrola pointed out on Twitter, it’s hard for doctors and patients to let go of first impressions:

— John Mandrola, MD (@drjohnm) September 25, 2018

Dr. David M. Becker put it even more bluntly in an op-ed in the Philadelphia Inquirer:

“The study results, when released, may show people will benefit from Vascepa, and potentially help some people live longer. But the process of releasing partial results via a ‘topline’ report is inherently flawed, self-serving, can cause misleading headlines, and is ripe for abuse,” he wrote.

If the Vascepa proves to be as beneficial as the initial results show, that will be a boon for cardiovascular care. But it’s far too soon to hail omega-3s as the “new paradigm in treatment,” as Amarin’s CEO is anticipating.

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