Early initiation of eicosapentaenoic acid and statin treatment is associated with better clinical outcomes than statin alone in patients with acute coronary syndromes: 1-year outcomes of a randomized controlled study

Nosaka, Kisato; Miyoshi, Toru; Iwamoto, Mutsumi; Kajiya, Masahito; Okawa, Keisuke; Tsukuda, Saori; Yokohama, Fumi; Sogo, Masahiro; Nakamura, Tomoyuki; Matsuo, Noriyuki; Hirohata, Satoshi; Ito, Hiroshi; Doi, Masayuki

doi:10.1016/j.ijcard.2016.11.105

Cited by 71 publications

(51 citation statements)

References 38 publications

(42 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, TG reduction lowers several inflammatory markers associated with CV risk, and subgroup and post hoc analyses of outcome studies suggest possible reductions in major CV events with TG‐lowering therapy 3, 4, 5, 6, 7, 8, 9, 10, 11. Finally, studies administering higher‐dose EPA suggest additional beneficial effects beyond lipid‐lowering that may be unique to EPA relative to other TG‐lowering therapies, such as beneficial changes in coronary plaque characteristics, which may lead to reductions in major CV events 4, 16, 25, 26, 27, 28, 29, 30, 31, 32, 33…”

Section: Discussionmentioning

confidence: 99%

“…In addition to beneficial changes to TG‐rich lipoproteins and other plasma lipid markers, some clinical studies with higher‐dose EPA also suggest beneficial effects on markers of oxidation and inflammation, coronary plaque characteristics, and major CV events 16, 25, 26, 29, 31, 32, 33. For example, in contrast to the fenofibrate and niacin studies, JELIS found a 19% relative risk reduction in CV events in statin‐treated patients with relatively normal TG but a more pronounced 53% reduction in the subgroup with mixed dyslipidemia, specifically TG ≥150 mg/dL and HDL‐C <40 mg/dL 4, 16.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rationale and design of REDUCE‐IT: Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial

Bhatt

Steg

Brinton

et al. 2017

Clinical Cardiology

171

129

View full text Add to dashboard Cite

Residual cardiovascular risk persists despite statins, yet outcome studies of lipid‐targeted therapies beyond low‐density lipoprotein cholesterol (LDL‐C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High‐dose eicosapentaenoic acid (EPA) reduces triglyceride‐rich lipoproteins without raising LDL‐C. Omega‐3s have postulated pleiotropic cardioprotective benefits beyond triglyceride‐lowering. To date, no large, multinational, randomized clinical trial has proved that lowering triglycerides on top of statin therapy improves cardiovascular outcomes. The Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE‐IT; NCT01492361) is a phase 3b randomized, double‐blinded, placebo‐controlled trial of icosapent ethyl, a highly purified ethyl ester of EPA, vs placebo. The main objective is to evaluate whether treatment with icosapent ethyl reduces ischemic events in statin‐treated patients with high triglycerides at elevated cardiovascular risk. REDUCE‐IT enrolled men or women age ≥45 years with established cardiovascular disease or age ≥50 years with diabetes mellitus and 1 additional risk factor. Randomization required fasting triglycerides ≥150 mg/dL and <500 mg/dL and LDL‐C >40 mg/dL and ≤100 mg/dL with stable statin (± ezetimibe) ≥4 weeks prior to qualifying measurements. The primary endpoint is a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina. The key secondary endpoint is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Several secondary, tertiary, and exploratory endpoints will be assessed. Approximately 8000 patients have been randomized at approximately 470 centers worldwide. Follow‐up will continue in this event‐driven trial until approximately 1612 adjudicated primary‐efficacy endpoint events have occurred.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rationale and design of REDUCE‐IT: Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial

Bhatt

Steg

Brinton

et al. 2017

Clinical Cardiology

171

129

View full text Add to dashboard Cite

show abstract

“…The relative reduction in major coronary events was comparable across a range of LDL-C levels, suggesting that reduction in serum LDL-C levels was not a key factor in the observed CV risk reduction [48]. Additional support for the potential role of EPA in CV risk reduction comes from a prospective, single-center, randomized, open-label trial of 241 Japanese patients with acute coronary syndrome undergoing primary percutaneous coronary intervention (PCI) [49]. Patients were randomized to EPA 1.8 g/day (purified ethyl ester) plus a statin (pitavastatin 2 mg/day) or statin alone [49].…”

Section: Imaging Methods Key Findings Angiographymentioning

confidence: 99%

“…Additional support for the potential role of EPA in CV risk reduction comes from a prospective, single-center, randomized, open-label trial of 241 Japanese patients with acute coronary syndrome undergoing primary percutaneous coronary intervention (PCI) [49]. Patients were randomized to EPA 1.8 g/day (purified ethyl ester) plus a statin (pitavastatin 2 mg/day) or statin alone [49]. Early initiation of EPA/statin within 24 h after successful PCI resulted in a significantly lower risk of CV events compared with statin alone (relative risk of CV events at 1 year, 9.2% for EPA/statin, and 20.2% for statin alone; absolute risk reduction 11%; P = 0.02) [49].…”

Section: Imaging Methods Key Findings Angiographymentioning

confidence: 99%

See 1 more Smart Citation

Can pleiotropic effects of eicosapentaenoic acid (EPA) impact residual cardiovascular risk?

Nelson¹,

True

et al. 2017

Postgraduate Medicine

View full text Add to dashboard Cite

Residual cardiovascular (CV) risk persists even in statin-treated patients with optimized low-density lipoprotein cholesterol (LDL-C) levels. Other pathways beyond cholesterol contribute to CV risk and the key to reducing residual risk may be addressing non-cholesterol risk factors through pleiotropic mechanisms. The purpose of this review is to examine the literature relating to the potential role of the omega-3 fatty acid eicosapentaenoic acid (EPA) in reducing residual CV risk. The literature shows that EPA can robustly lower plasma triglyceride (TG) levels without raising LDL-C levels and documents EPA to have a broad range of beneficial effects on the atherosclerotic pathway, including those on lipids, lipoproteins, inflammation, oxidation, phospholipid membranes, and the atherosclerotic plaque itself. Clinical imaging studies have consistently demonstrated that EPA decreases plaque vulnerability and prevents plaque progression. The evidence therefore points to a potential role for EPA to reduce residual CV risk. A large randomized study of statin-treated Japanese patients demonstrated that EPA ethyl ester reduced major coronary events by 19% (P = 0.011). However, while there has been significant benefit demonstrated in this and another Japanese CV outcomes study, the question as to whether EPA can play a role in reducing residual CV risk remains to be addressed in broader populations. The large, global, ongoing, randomized, placebo-controlled REDUCE-IT study of high-risk statin-treated patients with persistent hypertriglyceridemia is currently underway to investigate the potential of icosapent ethyl (high-purity prescription EPA ethyl ester) as an add-on therapy to reduce residual CV risk. ARTICLE HISTORY

show abstract

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease

Abdelhamid

Brown

Brainard

et al. 2018

Cochrane Database of Systematic Reviews

386

298

View full text Add to dashboard Cite

Early initiation of eicosapentaenoic acid and statin treatment is associated with better clinical outcomes than statin alone in patients with acute coronary syndromes: 1-year outcomes of a randomized controlled study

Abstract: UMIN Clinical Trials Registry (UMIN-CTR); Registry Number, UMIN000016723; URL, http://www.umin.ac.jp/ctr/index-j.htm.

Cited by 71 publications

References 38 publications

Rationale and design of REDUCE‐IT: Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial

Rationale and design of REDUCE‐IT: Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial

Can pleiotropic effects of eicosapentaenoic acid (EPA) impact residual cardiovascular risk?

Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease

Contact Info

Product

Resources

About