{"doi":"10.1093/ajcn/nqac055","title":"Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial","abstract":"BACKGROUND: Cocoa extract is a source of flavanols that favorably influence vascular risk factors in small and short-term trials, yet effects on clinical cardiovascular events are untested. OBJECTIVES: We examined whether cocoa extract supplementation decreases total cardiovascular disease (CVD) among older adults. METHODS: We conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of cocoa extract supplementation and multivitamins for prevention of CVD and cancer among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y), free of major CVD and recently diagnosed cancer. The intervention phase was June 2015 through December 2020. This article reports on the cocoa extract intervention. Participants were randomly assigned to a cocoa extract supplement [500 mg flavanols/d, including 80 mg (-)-epicatechin] or placebo. The primary outcome was a composite of confirmed incident total cardiovascular events, including myocardial infarction (MI), stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina. RESULTS: During a median follow-up of 3.6 y, 410 participants taking cocoa extract and 456 taking placebo had confirmed total cardiovascular events (HR: 0.90; 95% CI: 0.78, 1.02; P = 0.11). For secondary endpoints, HRs were 0.73 (95% CI: 0.54, 0.98) for CVD death, 0.87 (95% CI: 0.66, 1.16) for MI, 0.91 (95% CI: 0.70, 1.17) for stroke, 0.95 (95% CI: 0.77, 1.17) for coronary revascularization, neutral for other individual cardiovascular endpoints, and 0.89 (95% CI: 0.77, 1.03) for all-cause mortality. Per-protocol analyses censoring follow-up at nonadherence supported a lower risk of total cardiovascular events (HR: 0.85; 95% CI: 0.72, 0.99). There were no safety concerns. CONCLUSIONS: Cocoa extract supplementation did not significantly reduce total cardiovascular events among older adults but reduced CVD death by 27%. Potential reductions in total cardiovascular events were supported in per-protocol analyses. Additional research is warranted to clarify whether cocoa extract may reduce clinical cardiovascular events. This trial is registered at www.clinicaltrials.gov as NCT02422745.","journal":"American Journal of Clinical Nutrition","year":2022,"id":232616,"datarank":4.213670847298497,"base_score":5.19295685089021,"endowment":5.19295685089021,"self_citation_contribution":0.7789435276335317,"citation_network_contribution":3.4347273196649653,"self_endowment_contribution":0.7789435276335317,"citer_contribution":3.4347273196649653,"corpus_percentile":null,"corpus_rank":null,"citation_count":179,"citer_count":100,"citers_with_citation_signal":100,"citers_with_endowment":100,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT02422745"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":11268,"name":"JoAnn E. Manson","orcid":"0000-0002-9426-7595","position":1,"is_corresponding":false},{"id":243115,"name":"Aaron K. Aragaki","orcid":"0000-0001-5075-6437","position":2,"is_corresponding":false},{"id":302168,"name":"Pamela M. Rist","orcid":"0000-0003-3543-045X","position":3,"is_corresponding":false},{"id":710768,"name":"Lisa Johnson","orcid":null,"position":4,"is_corresponding":false},{"id":754356,"name":"Georgina Friedenberg","orcid":null,"position":5,"is_corresponding":false},{"id":700003,"name":"Trisha Copeland","orcid":null,"position":6,"is_corresponding":false},{"id":844943,"name":"Allison Clar","orcid":null,"position":7,"is_corresponding":false},{"id":351263,"name":"Samia Mora","orcid":"0000-0001-6283-0980","position":8,"is_corresponding":false},{"id":351260,"name":"M. Vinayaga Moorthy","orcid":"0000-0002-0983-3215","position":9,"is_corresponding":false},{"id":844944,"name":"Ara Sarkissian","orcid":null,"position":10,"is_corresponding":false},{"id":844945,"name":"William R Carrick","orcid":null,"position":11,"is_corresponding":false},{"id":243116,"name":"Garnet L. Anderson","orcid":"0000-0001-5087-7837","position":12,"is_corresponding":false},{"id":420934,"name":"Howard D. Sesso","orcid":"0000-0002-9698-9954","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-19T00:21:18.683916Z","pmid":"35294962","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":[]}