Cardiologists may one day have a new tool to help prevent heart attacks and strokes in some high-risk patients: a prescription drug that contains large doses of EPA, an omega-3 fatty acid contained in fish oil.
A large clinical trial found that the drug, called Vascepa, sharply reduced the rate of cardiovascular events in people with a history of heart disease or Type 2 diabetes, according to early results that were announced on Monday.
The findings were particularly relevant for people with high triglycerides, a type of fat in the blood that has been linked to an increased risk of heart disease. The new trial, called Reduce-IT, focused on people whose cholesterol levels were well controlled with statins but whose triglyceride levels remained very high. Many cardiovascular experts were doubtful that adding fish oil on top of statins would produce much if any benefit because a number of smaller and less rigorous studies over the years had failed.
But the new trial showed that statin-treated adults with elevated triglycerides who were prescribed high doses of the purified EPA had a 25 percent reduction in their relative risk of heart attacks, strokes and other cardiac events compared to a control group of patients who received placebo.
“I’m very surprised by the magnitude of the results, which quite frankly are large,” said Dr. Michael J. Blaha, the director of clinical research at the Ciccarone Center for the Prevention of Heart Disease at Johns Hopkins Medical School, who was not involved in the study. “My expectations were very low. A lot of people are legitimately surprised by this.”
Fish oil has long been a popular supplement to protect against heart disease. It contains high levels of omega-3 fatty acids, primarily EPA and DHA, which reduce inflammation and lower triglyceride levels. Omega-3 fatty acids also have blood-thinning effects similar to those of aspirin.
But until now most of the clinical trials that have looked at fish oil in heart patients had not found convincing evidence that it helps. Some argued that the trials were deeply flawed, saying they relied on doses that were too small or that they failed to recruit the patients who were most likely to benefit, like those with high triglycerides. Some of the studies were observational, which are less rigorous than clinical trials, in which different groups of patients receive different treatments. They also used various types of fish oil.
The new trial differed from previous ones in a number of ways. It focused specifically on two groups of high-risk patients: People with a history of cardiovascular events, such as heart attacks, strokes and angina; and those with Type 2 diabetes and other risk factors like high blood pressure. The patients also had to have high triglycerides. The median baseline level of triglycerides among the subjects was 216 milligrams per deciliter — well above the cutoff for what is considered a normal level, which is 150 milligrams per deciliter. In addition, all of the patients were on statins, which lower cholesterol.
The intervention in this trial, which was sponsored by Amarin, was not the typical fish oil supplement that can be purchased at any supermarket or pharmacy. Vascepa is a prescription drug that contains highly purified EPA. Fish oil supplements, on the other hand, often contain a mixture of both EPA and DHA and in some cases other oils as well. EPA and DHA are similar but have slightly different effects. Both can lower triglycerides, for example, but DHA also tends to raise LDL cholesterol, the so-called bad kind associated with heart disease.
The trial enrolled 8,179 adults and followed them on average for about five years. In addition to lowering cardiovascular events, the trial found that Vascepa was safe and well tolerated. Amarin announced the findings on Monday and is expected to present the full results and data at an annual American Heart Association conference in November.
Dr. Ethan Weiss, a cardiologist and associate professor at the University of California, San Francisco, who was not involved in the study, said that the findings confirm the role that high triglycerides play in heart disease but that they nonetheless came as a shock because so many earlier trials of fish oil found little or no benefits. He pointed to several caveats: He and others need to see all of the data, and the patient population that is likely to benefit from Vascepa is very specific. Diet and exercise can also lower triglycerides — especially very low carbohydrate diets — and whether the outcome on heart risk might be similar to the effect produced by Vascepa should be studied, he said.
“Lots of questions remain,” he said. “But the takeaway is that this is really big and I was wrong. And I am happy I was wrong and am excited we have a new pathway and set of tools to explore for our patients.”
Some experts cautioned that Vascepa is not for everyone who has heart disease or risk factors for it. The drug is currently approved for certain patients with unusually high triglyceride levels.
“The worried well shouldn’t run out and take fish oil,” said Dr. Michael Shapiro, a site investigator for the Reduce-IT trial and the director of Oregon Health and Science University’s Atherosclerosis Imaging Program. But the group that is likely to benefit includes a large proportion of patients in heart clinics.
“The amount of people around the world who have atherosclerotic disease or diabetes who take a statin and still have elevated triglycerides is enormous,” he said. “This has huge implications.”
