{"doi":"10.1093/eurheartj/ehad889","title":"Icosapent ethyl following acute coronary syndrome: the REDUCE-IT trial","abstract":"The REDUCE-IT [Reduction of Cardiovascular Events With Icosapent Ethyl (IPE)-Intervention Trial] trial showed robust reductions in ischaemic events with IPE vs. placebo, including reduced cardiovascular (CV) death, albeit with increased rates of bleeding, and of atrial fibrillation (AF).1 These observations were confirmed in patients with prior myocardial infarction (MI).2 Patients with recent (<12 months) acute coronary syndrome (ACS) are at very high risk of future CV events (including arrhythmias) for which they usually receive intensive antithrombotic therapy, which might increase bleeding risk with IPE. The benefit and safety of IPE in this specific patient subgroup are largely unknown and were explored in the present post hoc analysis of the original trial database. REDUCE-IT was a double-blind, placebo-controlled trial that randomized 8179 statin-treated patients with controlled low-density lipoprotein cholesterol and moderately elevated triglycerides, and with either established CV disease or with diabetes and at least one additional risk factor, to either 4 g IPE or placebo.1 The trial methods and results have previously been published.1,3 The primary outcome was a composite of CV death, non-fatal MI, non-fatal stroke, coronary revascularization, or hospitalization for unstable angina. The key secondary outcome was a composite of CV death, non-fatal MI, or non-fatal stroke. Recent ACS (n = 840) was defined as MI or unstable angina within 12 months before randomization. In subsequent analyses, this group was compared with patients experiencing ACS ≥12 months before randomization (n = 3651). Time-to-first event was analysed by Kaplan–Meier analysis and compared using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) were generated using a Cox proportional hazards model computed to determine the risk of primary and secondary outcomes according to the use of IPE vs. placebo in two-sided analyses. The model was stratified by the three randomization factors of CV risk category (established CV disease or diabetes plus risk factors), geographic region, and baseline ezetimibe use. Time-to-subsequent events was analysed using the Wei, Lin, and Weissfeld model to estimate HR and 95% CI for treatment effects. Total events were analysed by negative-binomial regression model to estimate rate ratio (RR) and 95% CI for treatment effects. Absolute risk reduction (ARR) was calculated as difference of event incidence rates between IPE and placebo. Statistical analyses were performed using SAS version 9.4 software (SAS Institute, Inc.). Among 8179 patients in REDUCE-IT, there were 840 (10.3%) with recent ACS <12 months before randomization. Median age was 59.5 years, 646 (76.9%) were male, 310 (36.9%) had diabetes, 839 (99.9%) were on statins, 805 (95.8%) received antiplatelet therapy, 584 (69.5%) received dual antiplatelet therapy (DAPT), 54 (6.4%) were on oral anticoagulant therapy, and 39 (4.6%) were on anticoagulant plus antiplatelet therapy. Median baseline triglyceride levels were 219.5 (interquartile range (IQR) 180.5–272.5) and 213.0 (IQR 174.0–274.0) mg/dL in the IPE and placebo groups, respectively (P = .36). The median time elapsed between the index ACS and randomization was similar between IPE and placebo arms {5.5 (IQR 3.0–8.1) vs. 5.6 (IQR 3.2–8.4) months; P = .63}. Among recent ACS patients, use of anti-diabetic, anti-hypertensive, angiotensin-converting enzyme inhibitor, or beta-blocker therapies was similar between treatment arms, but DAPT use was lower in the IPE group compared with the placebo group (66.3% vs. 73.0%, P = .04), and rates of anticoagulant plus antiplatelet therapy were higher in the IPE group (6.2% vs. 2.9%, P = .02). Median study follow-up time was 4.75 years. Maximum follow-up time was 5.94 years. Icosapent ethyl reduced the incidence of the first primary composite outcome by 37% (HR 0.63; 95% CI 0.48–0.84, P = .002) and total primary composite outcomes by 36% (RR 0.64; 95% CI 0","journal":"European Heart Journal","year":2024,"id":421491,"datarank":0.5101796072493234,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.0,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":3774,"name":"Deepak L. Bhatt","orcid":"0000-0002-1278-6245","position":1,"is_corresponding":false},{"id":336282,"name":"Michael Miller","orcid":"0000-0002-1679-2095","position":2,"is_corresponding":false},{"id":500812,"name":"Eliot A. Brinton","orcid":"0000-0002-9807-4010","position":3,"is_corresponding":false},{"id":242862,"name":"Terry A. Jacobson","orcid":"0000-0002-9926-2179","position":4,"is_corresponding":false},{"id":1058298,"name":"Steven Ketchum","orcid":"0000-0002-9302-4743","position":5,"is_corresponding":false},{"id":1058300,"name":"Lixia Jiao","orcid":"0000-0001-7003-4925","position":6,"is_corresponding":false},{"id":1213859,"name":"Armando Lira Pineda","orcid":"0000-0002-1746-3162","position":7,"is_corresponding":false},{"id":1058964,"name":"Ralph T. Doyle","orcid":null,"position":8,"is_corresponding":false},{"id":22052,"name":"Jean‐Claude Tardif","orcid":"0000-0002-8200-8983","position":9,"is_corresponding":false},{"id":233725,"name":"Christie M. Ballantyne","orcid":"0000-0002-6432-1730","position":10,"is_corresponding":false},{"id":79684,"name":"Philippe Gabríel Steg","orcid":"0000-0001-6896-2941","position":11,"is_corresponding":false},{"id":1213858,"name":"Neila Sayah","orcid":"0009-0009-0473-9623","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:57:36.298171Z","pmid":"38252107","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}