Cholesterol-lowering drugs may one day gain a sidekick in the battle against heart disease. Taking a potent drug derived from fish oil along with a statin lowers the risk of heart attack and stroke in some high-risk people, researchers report.
A clinical trial called REDUCE-IT tested the approach in more than 8,000 participants who either had cardiovascular disease or were at high risk for it. These people were already on statins to lower their cholesterol, and also had high levels of fats called triglycerides in their blood. Elevated triglycerides can increase one’s risk of heart attack and stroke.
People took either a two-gram pill of a highly purified omega-3 fatty acid — the oil found in fatty fish — twice daily or a placebo, and were followed up to six years. Of the omega-3 group, 17.2 percent had a fatal or nonfatal heart attack or stroke, compared with 22 percent in the placebo group.
Overall, the omega-3 drug, called Vascepa, reduced the risk of heart attack or stroke by 25 percent, researchers announced November 10 at the American Heart Association’s annual scientific sessions in Chicago and in a study published online the same day in the New England Journal of Medicine.
The results are “strikingly positive,” says cardiologist Carl Orringer of the University of Miami Miller School of Medicine who was not involved in the study. For people taking statins and working to combat high levels of triglycerides with healthy diet and exercise, the new drug appears to provide additional benefit, he says.
But it’s possible that benefit may not be as large as it seems. That’s because the placebo that the researchers used was made of mineral oil, which can interfere with the absorption of statins, thereby lowering the statin dose, says cardiologist Steven Nissen at the Cleveland Clinic who was not involved in the study. He wonders if the drug’s positive effect may be partly due to people on the placebo being somewhat worse off. Nissen is leading a clinical trial of a different omega-3 drug that is using corn oil for the placebo.
People take statins primarily to reduce the amount of “bad” cholesterol, called LDL cholesterol, in the blood. Both groups in the trial did have a small increase in LDL cholesterol, with the placebo group’s increase higher than the omega-3 group’s. But, the researchers say, this small difference isn’t likely to account for the 25 percent reduction in risk between the groups.
Orringer agrees. “Even if there was a slight effect of mineral oil, it would be so minimal that I don’t believe there is any way that this could account for the striking difference seen” between those on the omega-3 drug and those not, he says.
Cardiovascular disease is the leading cause of death for both men and women in the United States and accounts for approximately 800,000 deaths each year. High LDL cholesterol is one risk factor for the disease. Excess LDL cholesterol contributes to the buildup of plaques in artery walls, and it’s considered high when it’s at or above 160 milligrams of cholesterol per deciliter of blood.
For some patients taking statins, doctors also monitor triglycerides in the blood, because high levels of the fats can increase the risk of heart attack and stroke. Conditions like obesity and diabetes can lead to high triglyceride levels — those at or above 200 milligrams per deciliter of blood.
Vascepa has already been approved by the U.S. Food and Drug Administration to lower triglycerides in people with very high levels (500 milligrams per deciliter of blood or higher). In the new Phase III clinical trial — conducted to gain approval for the drug’s use in a different group of people — preventive cardiologist Christie Ballantyne and colleagues tested whether the drug could help prevent heart attacks and strokes in heart disease patients and in those with risk factors like diabetes. Study participants’ triglyceride levels were mostly borderline high or high, from 150 to 499 milligrams per deciliter; this is lower than the level for which Vascepa is already approved.
The resulting drop in heart-related health risk is “very encouraging,” says Ballantyne, of Baylor College of Medicine in Houston. Diet and exercise are important for reducing triglycerides, Ballantyne says. But if a patient with heart disease on statins is making lifestyle changes and his or her triglyceride levels are still high, “this treatment could be of benefit,” he says.
Surprisingly, while the drug did lower triglyceride levels, the change probably wasn’t enough to fully explain the reduced heart attack and stroke risk, Ballantyne says, so Vascepa may have additional effects.
Still, the finding that a particular omega-3 drug helped some high-risk patients doesn’t mean that popular, but less potent, supplements containing omega-3 fatty acids have a similar effect, says Orringer. “We don’t want people to go running out to the drugstore to buy a fish oil pill. It won’t help them.”
A number of studies of less potent fish oil pills and other triglyceride-lowering drugs haven’t shown similar cardiovascular benefits. For example, a clinical trial called VITAL found that taking an omega-3 supplement didn’t help lower heart disease risk in a broader and more generally healthy population than that studied in the REDUCE-IT trial. That finding was presented November 10 at the American Heart Association’s meeting.