Deborah Brauser

March 17, 2015

SAN DIEGO, CA — Although lively debate has raged about whether fish-oil supplementation (FOS) really is beneficial for preventing cardiovascular events, new research suggests that it may reduce the "overall atherothrombotic risk profile" in patients with suspected CAD[1].

Results from the Multi-Analyte, Thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA) study, presented in a poster here at the American College of Cardiology (ACC) 2015 Scientific Sessions, showed a significant association between FOS and decreased inflammation, thrombogenicity, and lipid markers. The effect was especially strong for those who were not taking lipid-lowering medications vs those who were, with significantly lower LDL-C, total VLDL-C, and triglycerides.

"In clinical-trial data, there's a lot of controversy about whether these supplements really affect outcomes," lead author Dr Paul A Gurbel (Sinai Center for Thrombosis Research, Baltimore, MD), told heartwire from Medscape.

"But if we personalize therapy with the fish oil to assess response based on fairly validated biomarkers, then I think there's hope for fish oil as a beneficial antithrombotic strategy—and maybe a competitor for statins," added Gurbel.

Although past research has shown that omega-3 polyunsaturated fatty acids (PUFAs) from fish oil are associated with cardiovascular benefits, how FOS affects thrombosis is "incompletely understood," note the investigators.

For the current study, they sought to measure lipid profile, inflammation, and thrombogenicity markers by using thromboelastography, aggregation, and "urinary 11-dehydrothromoxane B2 immediately prior to elective coronary angiography." Vertical density-gradient ultracentrifugation and AtherOx tests were also used.

A total of 600 patients with suspected CAD were enrolled in MAGMA. Of these, 128 were on FOS (67.2% men; mean age 64.4 years; body-mass index [BMI] 30.7) vs 472 who were not (61.7% mean; mean age also 64.4 years; BMI 30.9). In addition, 70.3% of the FOS group was on lipid-lowering therapy (including statins, nonstatins, or both) vs 71.2% of the non-FOS group.

Significant Results

"This is a study we've been doing in our hospital of patients who have come to our cath laboratory. And we found some interesting results," reported Gurbel.

In the entire patient population as a whole, taking FOS was significantly associated with lower total VLDL-C (P=0.002), intermediate-density-lipoprotein cholesterol (P=0.02), triglycerides (P=0.04), and AtherOx-tested levels (P=0.02) vs not taking FOS. They also had significantly lower urinary 11-dehydrothromboxane B2 levels (P=0.0007).

Patients who took FOS and were not on lipid-lowering medications also showed significantly lower levels of these measures, as well as lower LDL-C, remnant lipoproteins, and collagen-induced platelet aggregation. On the thrombogenicity profile, they also had lower thrombin-induced platelet fibrin clot strength (P=0.01) and "G," signifying clot firmness (P=0.0003).

FOS was not significantly associated with an influence on any of these measures in patients who also took statins.

Overall, the findings suggest that FOS "may have its most potent antiatherothrombotic effects in patients not on lipid-lowering therapy," write the investigators, adding that future studies should actually compare effects from FOS vs statins.

"We really need to look at how these biomarkers in response to fish oil correlate with clinical outcomes. For example, if there's an anti-inflammatory response to fish oil, maybe that's a reason to keep a patient on fish oil. That's the kind of personalization that we're interested in," said Gurbel.

"Good News," but Outcomes Trials Needed

Dr Norman E Lepor (Cedars Sinai Medical Center, Los Angeles, CA) echoed Gurbel's comments to heartwire that the issue of using FOS "has been quite controversial" because of the lack of prospective, randomized outcome studies.

"At this moment, we don't really know whether fish oil prevents cardiovascular events. What's interesting is that this study looked at its effect on a variety of specific indicators of the propensity to clot and for the development of inflammation," said Lepor, who is not involved with this research.

"We can't necessarily correlate that benefits with either one or both of these will lead to a reduction in heart attacks, stroke, and death, which is what we're really concerned about," he noted. "However, these data show that patients who take [FOS] seem less predisposed to blood clotting, their platelets seemed less sticky, and at least the components of inflammation that were measured in the trial were reduced."

So, there is evidence that FOS provides some benefits, he said, adding that this is good news for cardiologists.

"But we're still waiting for clinical data that answer, at the end of the day: if we give these to patients, will they live longer? Are they less likely to have a heart attack? It's really the outcomes that's going to drive cardiologists to prescribe these medications."

Lepor noted that FOS is readily accepted now by the public and is often used by cardiologists to treat high triglyceride levels. However, "you'll see me prescribe more fish oils once we have the outcome data showing that there is a reduction in actual events."

The study was support by Sinai Center for Thrombosis Research. Gurbel reports receiving consultant fees and honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi-Sankyo, Lilly, and Merck and receiving research grants from AstraZeneca, the National Institutes of Health, Daiichi-Sankyo, CSL, Harvard Clinical Research Institute, Haemonetics, and Duke Clinical Research. Lepor reports being an investigator on the ongoing REDUCE-IT trial, which is examining effects of FOS.

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