Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial

• Published in: The American journal of clinical nutrition 2022-06, Vol.115 (6), p.1490-1500
• Main Authors: Sesso, Howard D, Manson, JoAnn E, Aragaki, Aaron K, Rist, Pamela M, Johnson, Lisa G, Friedenberg, Georgina, Copeland, Trisha, Clar, Allison, Mora, Samia, Moorthy, M Vinayaga, Sarkissian, Ara, Carrick, William R, Anderson, Garnet L
• Format: Article
• Language: English
• Subjects: Adults; Aged; Angina; Cacao; Cancer; Cardiovascular disease; Cardiovascular Diseases; Carotid artery; Cerebral infarction; Clinical trials; Cocoa; cocoa extract; Death; Dietary Supplements; Diuretics; Double-Blind Method; Editor's Choice; Epicatechin; Female; Flavanols; Health risks; Heart diseases; Humans; Male; Mortality; multivitamin; Myocardial infarction; Myocardial Infarction - prevention & control; Neoplasms - prevention & control; Older people; Original Research Communications; Placebos; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Polyphenols; Prevention; randomized clinical trial; Risk analysis; Risk Factors; Stroke - drug therapy; Stroke - epidemiology; Stroke - prevention & control; Supplements; Vitamins - therapeutic use
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.1093/ajcn/nqac055

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. We examined whether cocoa extract supplementation decreases total cardiovascular disease (CVD) among older adults. 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. 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. 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. ▪