The safety and efficacy of direct oral anticoagulants (DOACs) for extended anticoagulation were associated with significant overall reductions in mortality compared with observation alone, according to a study published in CHEST. This systematic review and meta-analysis was designed to assess the effects of DOACs and vitamin K antagonists (VKAs) during extended anticoagulation for venous thromboembolism (VTE) on VTE-related and overall mortality, as well as safety and VTE recurrence. Researchers searched the Cochrane Library, EMBASE, and PubMed for randomized controlled trials that compared extended anticoagulants for VTE with placebo published between January 1990 and September 2018.
A total of 16 studies with 12,458 total participants were included in the analysis. DOACs were associated with a reduction in VTE-related mortality (risk ratio [RR], 0.36; 95% CI, 0.15-0.89; P =.03) and in overall mortality (RR, 0.48; 95% CI, 0.27-0.86; P =.01), but VKAs were not (RR, 1.17; 95% CI, 0.64-2.13; P =.61). Although both DOACs and VKAs similarly prevented recurrent VTE, VKAs were associated with increased risk of major bleeding (RR, 2.67; 95% CI, 1.28-5.60; P <.01), which resulted in an improved net clinical benefit for DOACs (RR, 0.25; 95% CI, 0.16-0.39; P <.01 vs RR, 0.46; 95% CI, 0.30-0.72; P <.01).
The investigators concluded that “extended anticoagulation with DOACs is associated with a reduction in overall and VTE-related mortality, which is not the case for VKAs. Although extended anticoagulation with both DOACs and VKAs was associated with a lower relative risk of recurrent events, VKAs were also associated with an increase in [major bleeding]. These comparisons, however, are only indirect and should be interpreted with caution in the absence of head-to-head comparisons.”
Disclosures: The researchers have reported receiving speaking/consulting fees or unrelated grants from Actelion Pharmaceuticals, Aspen, Bayer, Boehringer Ingelheim, BMS-Pfizer, and Daiichi Sankyo.
Mai V, Guay C-A, Perreault L, et al. Extended anticoagulation for VTE: A systematic review and meta-analysis. CHEST. 2019;155(6):1199-1216.