Non-vitamin K antagonist oral anticoagulants ( NOACs ) are efficacious and safe antithrombotic drugs but the non-availability of an antidote for potential fatal haemorrhagic events is clinically perceived as a strong limitation.
Researchers aimed at evaluating the risk of haemorrhage-related fatalities associated with non-vitamin K antagonist oral anticoagulants in patients requiring long-term anticoagulation.
Eleven studies were included in systematic review and meta-analysis: 5 on atrial fibrillation and 6 on venous thromboembolism. A total of 100 324 patients were evaluated in 4 Rivaroxaban, 3 Dabigatran, 2 Apixaban and 2 Edoxaban studies.
NOAC-treated patients had a 47% odds reduction compared with vitamin K antagonist ( VKA ) ( odds ratio, OR=0.53; 95% CI 0.42 to 0.68; I2=0%; 3 events avoided per 1000 patients ) and 64% odds reduction compared with low-molecular-weight heparin [ LMWH ] – vitamin K antagonist [ VKA ] ( OR=0.36; 95% CI 0.15 to 0.84; I2=0%; 1 event avoided per 1000 patients ) regarding fatal bleeding risk.
Case fatality due to major bleeding was lower in NOAC-treated patients both in atrial fibrillation ( OR=0.68; 95% CI 0.48 to 0.96; I2=37%; 1 death avoided per 39 major bleedings ) and venous thromboembolism ( OR=0.54; 95% CI 0.22 to 1.32; I2=0% ) patients.
Atrial fibrillation survivors of major bleeding events treated with NOACs had lower mortality compared with patients treated with vitamin K antagonists ( OR=0.57; 95% CI 0.45 to 0.73; I2=0%; 78 events avoided per 1000 survivors to major bleeding ).
In conclusion, these data suggest that non-vitamin K antagonist oral anticoagulants decrease the risk of fatality cases related to major bleeding events, particularly in patients with atrial fibrillation.
These results support the safety profile of non-vitamin K antagonist oral anticoagulants even without having a widely available drug-specific antidote. ( Xagena )
Caldeira D et al, Heart 2015;101:1204-1211