‘Possible’ benefit with highly purified EPA to reduce CV risk in CAD with statin therapy
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CHICAGO — In Japanese adults with chronic CAD already treated with statin therapy, highly purified eicosapentaenoic acid showed borderline statistical significance in reducing risk for adverse CV events, researchers reported.
Data from the RESPECT-EPA trial, presented at the American Heart Association Scientific Sessions indicate a “possible prognostic benefit” of daily eicosapentaenoic acid (EPA), particularly in adults with chronic CAD whose EPA/arachidonic acid (AA) ratio is low, Hiroyuki Daida, MD, PhD, FACC, of Juntendo University School of Medicine, Tokyo, said during a late-breaking science presentation.
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High-intensity statin therapy has become the standard of care for people with CAD; however, patients are still at substantially high residual risk for events, Daida said.
“Despite evidence from the JELIS trial, conflicting results in recent omega-3 fatty acid trials have led to intense controversy regarding the relevance of EPA intervention on top of background statin therapy,” Daida said. “Our objective was to determine the benefit of highly purified EPA on CV events in Japanese chronic CAD patients with a low EPA:AA ratio who received statins.”
EPA with statin therapy
Daida and colleagues analyzed data from 3,844 adults with chronic CAD receiving statins for at least 1 month before study inclusion. Researchers randomly assigned participants to 1,800 mg daily EPA in the form of icosapent ethyl (marketed in the U.S. as Vascepa by Amarin; n = 1,249) or a control group (n = 1,257); additionally, 1,338 patients were included in a high-EPA:AA group. The median age of participants was 68 years, 82.7% were men, about 45% had diabetes and the majority had hypertension and a history of CVD.
The primary endpoint was a composite of CV death, nonfatal MI, nonfatal cerebral infarction, unstable angina requiring emergency hospitalization and coronary revascularization procedure, and revascularization procedure based on clinical findings. The secondary endpoint was a composite of CAD events, composite stroke events and events related to death.
At 4 years, researchers observed a slight variation numerically in the primary endpoint in favor of EPA (8.6% vs. 8.8%; HR = 0.785; 95% CI, 0.616-1.001; P = .0547), which continued to grow and favor EPA at 6 years (10.9% vs. 14.9%), Daida said.
The secondary endpoint occurred less often at 4 years in the EPA group than in the control group (6.6% vs. 7.6%; HR = 0.734; 95% CI, 0.554-0.973; P = .0306), and the difference grew at 6 years (8% in the EPA group vs. 11.3% in the control group), according to the researchers.
There was no difference between the groups in all-cause mortality or CV mortality at 4 years, but CV mortality favored the EPA group at 6 years (2% vs. 3%), Daida said.
“There was a trend of lower revascularization in the EPA group,” he said.
Safety data; post hoc analysis
Assessing safety, Daida noted that a “small but significant increase” in new-onset atrial fibrillation was more common in the EPA group compared with controls (3.1% vs. 1.6%; P = .017), as were gastrointestinal disorders (3.4% vs. 1.2%; P < .001).
In a post hoc analysis that excluded participants whose EPA increased by more than 30 µg/mL from the control group (n = 1,053) and excluded participants in the EPA group whose EPA did not increase by more than 30 µg/mL (n = 966), the primary endpoint reached statistical significance, with an HR of 0.725 (95% CI, 0.553-0.951; P = .0202).
“Although this is post hoc, we think this is important information,” Daida said.
Daida noted that the actual event rate in the study was lower than estimated and the study was likely underpowered. Additionally, most participants were Japanese, whose baseline EPA level is considered to be higher than in most individuals from Western countries.
Consider EPA for residual risk
Discussing the RESPECT-EPA findings, Pam R. Taub, MD, FACC, FASPC, professor of medicine at the University of California, San Diego, said the topic of EPA is “very polarizing” in cardiology; however, the data reflect that EPA shows benefit in decreasing composite coronary events, despite being an underpowered trial.
“There is benefit with EPA, but the magnitude of benefit is uncertain,” Taub said.
Taub said more mechanistic and clinical data are needed to better determine which patients will derive the most benefit, such as those with elevated high-sensitivity C-reactive protein or the highest change in delta EPA level.
“One thing that is consistent across all of these [EPA] studies is the risk for AF,” Taub said. “Though it is rather small, it is something that we need to pay attention to and understand better mechanistically. In terms of our patients with residual risk, we should still consider EPA as a molecule to institute for these patients.”
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Daida H, et al. LBS.05: Changing How We Prevent Cardiovascular and Renal Disease. Presented at: American Heart Association Scientific Sessions; Nov. 5-7, 2022; Chicago (hybrid meeting).
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