A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins

Watanabe, Tetsu; Ando, Kaoru; Daidoji, Hyuma; Otaki, Yoichiro; Sugawara, Satoshi; Matsui, Motoyuki; Ikeno, Eiichiro; Hirono, Osamu; Mikami, Hiroshi; Yashiro, Yoshinori; Nishiyama, Satoshi; Arimoto, Takanori; Takahashi, Hiroki; Shishido, Tetsuro; Miyashita, Takehiko; Miyamoto, Takuya; Kubota, Isao; investigators, Cherry study

doi:10.1016/j.jjcc.2017.07.007

Cited by 147 publications

(112 citation statements)

References 35 publications

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“…Nonetheless, patient background (including mean LDL cholesterol and triglyceride concentrations), except for EPA/arachidonic acid ratio, was not statistically different between the two groups ( P = 0.803, Table ). Watanabe et al showed that lipid volume and plaque volume reductions with EPA therapy were independent of decreases in LDL cholesterol and triglyceride concentrations, which is consistent with our results.…”

Section: Discussionsupporting

confidence: 93%

“…Several intravascular ultrasound or computed tomography studies have shown that EPA therapy attenuates plaque instability . In the present study, multiple regression analyses indicated that previous EPA administration was one of the independent predictors of the characteristics of unstable plaques (Tables ).…”

Section: Discussionsupporting

confidence: 60%

“…Several coronary computed tomography studies have shown that coronary plaques had lower plaque burden in patients receiving EPA therapy than in those not receiving EPA therapy . Furthermore, intravascular ultrasound studies have indicated smaller coronary atherosclerotic plaque or lipid volume in patients on EPA therapy than in those not on EPA therapy . However, no study has comprehensively examined whether EPA therapy is associated with decreased plaque instability in patients undergoing percutaneous coronary intervention (PCI) using OFDI.…”

Section: Introductionmentioning

confidence: 99%

“…15,16 Furthermore, intravascular ultrasound studies have indicated smaller coronary atherosclerotic plaque or lipid volume in patients on EPA therapy than in those not on EPA therapy. 17,18 However, no study has comprehensively examined whether EPA therapy is associated with decreased plaque instability in patients undergoing percutaneous coronary intervention (PCI) using OFDI. This study aimed to investigate the association between EPA therapy and coronary plaque instability in patients undergoing PCI using OFDI.…”

Section: Introductionmentioning

confidence: 99%

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Eicosapentaenoic acid therapy is associated with decreased coronary plaque instability assessed using optical frequency domain imaging

Konishi

Sunaga

Funayama

et al. 2019

Clinical Cardiology

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Background The relationship between eicosapentaenoic acid (EPA) therapy and coronary plaque stability assessed by optical frequency domain imaging (OFDI) has not been thoroughly described. Hypothesis EPA therapy is associated with decreased plaque instability in patients undergoing percutaneous coronary intervention (PCI) using OFDI. Methods Data on coronary artery plaques from 121 patients who consecutively underwent PCI between October 2015 and July 2018 were retrospectively analyzed. Of these patients, 109 were untreated (no‐EPA group), whereas 12 were treated with EPA (EPA group). Each plaque's morphological characteristics were analyzed using OFDI. Results We used 1:4 propensity score matching for patients who received or did not receive EPA therapy before PCI. Baseline characteristics were balanced between both groups (age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, smoking, previous PCI or coronary artery bypass grafting, previous myocardial infarction, prior statin use, acute coronary syndrome, hemoglobin A1c level, low‐density lipoprotein cholesterol concentration, triglyceride concentration, and high‐density lipoprotein cholesterol concentration). OFDI data from 60 patients were analyzed in this study. The EPA group had significantly lower mean lipid index (818 ± 806 vs 1574 ± 891) and macrophage grade (13.5 ± 5.9 vs 19.3 ± 7.4) but higher mean minimum fibrous cap thickness (109.2 ± 55.7 vs 81.6 ± 36.4 μm) than the no‐EPA group ( P = 0.010, 0.019, and 0.040, respectively). Multiple logistic regression analyses showed that prior EPA use was independently associated with lower lipid index and macrophage grade ( P = 0.043 and 0.024, respectively). Conclusion This OFDI analysis suggests that EPA therapy is associated with decreased plaque instability in patients undergoing PCI.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Eicosapentaenoic acid therapy is associated with decreased coronary plaque instability assessed using optical frequency domain imaging

Konishi

Sunaga

Funayama

et al. 2019

Clinical Cardiology

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“…After 3.2‐year follow‐up, those with phospholipid DHA levels above the median had less atherosclerosis progression as measured with coronary angiography. Two studies in Japanese patients have shown a significant additional benefit of EPA (1800 mg/day) added to statin therapy compared with statin alone on coronary plaque volume, as measured with integrated backscatter intravascular ultrasound 44, 45. In a post‐hoc analysis of 50 diabetics who were randomized to pravastatin or pitavastatin after percutaneous intervention and followed for 8 months, only low DHA levels remained significantly associated with atheroma progression measured by intravascular ultrasound after multivariate regression analysis 46.…”

Section: Discussionmentioning

confidence: 99%

Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial

Alfaddagh

Elajami

Ashfaque

et al. 2017

JAHA

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BackgroundAlthough statins reduce cardiovascular events, residual risk remains. Therefore, additional modalities are needed to reduce risk. We evaluated the effect of eicosapentaenoic acid and docosahexaenoic acid in pharmacologic doses added to statin treatment on coronary artery plaque volume.Methods and ResultsA total of 285 subjects with stable coronary artery disease on statins were randomized to omega‐3 ethyl‐ester (1.86 g of eicosapentaenoic acid and 1.5 g of docosahexaenoic acid daily) or no omega‐3 (control) for 30 months. Coronary plaque volume was assessed by coronary computed tomographic angiography. Mean (SD) age was 63.0 (7.7) years; mean low‐density lipoprotein cholesterol ≤80 mg/dL. In the intention‐to‐treat analysis, our primary endpoint, noncalcified plaque volume, was not different between groups (P=0.14) but approached significance in the per protocol analysis (P=0.07). When stratified by age in the intention‐to‐treat analysis, younger omega‐3 subjects had significantly less progression of the primary endpoint, noncalcified plaque (P=0.013), and fibrous, calcified and total plaque. In plaque subtype analysis, controls had significant progression of fibrous plaque compared to no change in the omega‐3 ethyl‐ester group (median % change [interquartile range], 5.0% [−5.7, 20.0] versus −0.1% [−12.3, 14.5], respectively; P=0.018). Among those on low‐intensity statins, omega‐3 ethyl‐ester subjects had attenuation of fibrous plaque progression compared to controls (median % change [interquartile range], 0.3% [−12.8, 9.0] versus 4.8% [−5.1, 19.0], respectively; P=0.032). In contrast, those on high‐intensity statins had no difference in plaque change in either treatment arm.ConclusionsHigh‐dose eicosapentaenoic acid and docosahexaenoic acid provided additional benefit to statins in preventing progression of fibrous coronary plaque in subjects adherent to therapy with well‐controlled low‐density lipoprotein cholesterol levels. The benefit on low‐intensity statin, but not high‐intensity statin, suggests that statin intensity affects plaque volume.Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01624727.

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Omega-3 Fatty Acids Effect on Major Cardiovascular Events in Patients at High Cardiovascular Risk

Olshansky

Bhatt

Chung

2021

JAMA

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A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins

Cited by 147 publications

References 35 publications

Eicosapentaenoic acid therapy is associated with decreased coronary plaque instability assessed using optical frequency domain imaging

Eicosapentaenoic acid therapy is associated with decreased coronary plaque instability assessed using optical frequency domain imaging

Effect of Eicosapentaenoic and Docosahexaenoic Acids Added to Statin Therapy on Coronary Artery Plaque in Patients With Coronary Artery Disease: A Randomized Clinical Trial

Omega-3 Fatty Acids Effect on Major Cardiovascular Events in Patients at High Cardiovascular Risk

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