(OR04-05-24) Effects of Cocoa Flavanol Supplementation on the Risk of Venous Thromboembolism: Post-Hoc Analysis of the COSMOS Trial

Objectives: Smaller short-term dietary intervention trials suggest cocoa flavanols may attenuate arterial risk factors; however, effects on clinical venous thromboembolic events have been untested. We examined whether daily cocoa extract (CE) supplementation or a daily multivitamin-multimineral (MVM) supplement decreases incident venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) among older adults.

Methods: We performed a post-hoc analysis of data from the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), a completed large-scale, randomized, placebo-controlled, 2-by-2 factorial trial that tested CE (including 500 mg/d cocoa flavanols) and MVM (as Centrum Silver) supplements in the prevention of cardiovascular disease and cancer among 21,442 U.S. adults (12,666 women aged ≥65 years and 8,776 men aged ≥60 years). Our primary outcome was self-reported incident VTE (composite for DVT and PE), and our co-secondary outcomes were incident DVT and PE. We conducted intention-to-treat and per-protocol analyses adjusting for trial design variables including age, sex, recruitment source, and the other randomized intervention.

Results: During a median follow-up of 3.5 years, there were 277, 165, and 379 cases of incident DVT, PE, and VTE, respectively. Those randomized to CE versus placebo had non-significant reductions in incident VTE (HR: 0.89; 95% CI: 0.72, 1.08), DVT (HR: 0.92; 95% CI: 0.73, 1.17), and PE (HR: 0.90; 95% CI: 0.66, 1.22). In cumulative incidence curves, any beneficial effects for CE appeared after 2 years of follow-up. There was no effect of a daily MVM on VTE, DVT, or PE. In per-protocol analyses that censored participants due to non-compliance or loss-to-follow-up, we observed a significant 21% reduction in VTE (95% CI: 0.63, 0.99) from MVM supplementation (p=0.04).

Conclusions: Daily CE or MVM supplementation did not significantly reduce the risk of incident VTE in older adults; however, potential protective effects from MVM on VTE when accounting for non-compliance. Future studies are needed to clarify whether CE or MVM may reduce thromboembolic events.

Funding Sources: COSMOS is supported by grants from Mars Edge and the National Institutes of Health. Haleon provided support of study pills and packaging.