Effects of Cocoa Extract and Multivitamin Supplementation on Venous Thromboembolism in the COSMOS Trial

Epidemiological and experimental studies suggest cocoa flavanols and multivitamin-multimineral (MVM) supplements may confer arterial vascular benefits. However, their effects on clinical venous thromboembolic events have been infrequently examined.To evaluate whether cocoa extract (CE) or MVM supplementation reduces the risk of venous thromboembolism (VTE) among older adults.We conducted an ancillary study analysis of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), a completed randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of CE and MVM supplementation for the prevention of cardiovascular disease and cancer among 21,442 older US adults. Our primary outcome was self-reported incident VTE, defined as the first reported deep vein thrombosis (DVT) or pulmonary embolism (PE) event after randomization; secondary outcomes were the individual components.Over a median follow-up of 3.5 years, 379 participants reported an incident VTE event (including 277 DVT and 165 PE). In intention-to-treat analyses, neither CE (HR: 0.88; 95% CI: 0.72, 1.08) nor MVM (HR: 0.89; 95% CI: 0.73, 1.09) significantly reduced VTE risk, with similar findings for DVT and PE. Exploratory latency and per-protocol analyses suggested potential patterns of benefit that merit further evaluation.In this large trial of older adults, neither CE nor MVM supplementation significantly reduced the risk of VTE or its component parts in intention-to-treat analyses. Additional research may help clarify whether these supplements influence VTE risk in other contexts or populations.