In key trials, dabigatran 150 mg (RE-LY trial) and apixaban (ARISTOTLE trial) both reduced the incidence of stroke/systemic embolism compared with warfarin based on analysis of the intention-to-treat trial populations.31,32
Rivaroxaban (ROCKET-AF trial) and dabigatran 110 mg (the indicated dose in Australia for people > 75 years)21 were non-inferiorc to, but not better than, warfarin for the incidence of stroke/systemic embolism based on analysis of the intention-to-treat trial populations.31,33
Participants in the warfarin arms of the rivaroxaban, apixaban and dabigatran key trials had a mean TTRd of 55%, 62.2% and 64%, respectively.31-33 When warfarin was well controlled (≥ 66% TTR34) dabigatran (110 mg and 150 mg) and apixaban were non-inferior to warfarin for the incidence of stroke/systemic embolism.31,32
Non-inferiority was not shown by rivaroxaban for incidence of stroke/systemic embolism when warfarin was well controlled.33,35,36 Only apixaban was better than warfarin for reducing major bleeding when warfarin was well controlled.32,34,e
Participants in the key trials all had non-valvular AF. Participants in the rivaroxaban study had at least two additional risk factors for stroke and a mean CHADS2 score of ~3.5 whereas participants in the dabigatran and apixaban trials had at least one additional risk factor for stroke and an average CHADS2 score of 2.1–2.2 and 2.1, respectively.31-33
Concomitant use of anticoagulant and aspirin was permitted in both arms of the trials, which may have affected safety outcomes.31-33
The newer oral anticoagulants are associated with reduced incidence of ICH compared with warfarin, but absolute risk reductions in trials were small and rivaroxaban and dabigatran (150 mg) had increased incidences of GI bleeds (Table 5).31-33 Incidence of death after ICH was similar with warfarin and dabigatran in trials.37
c Non-inferior: the effect of a new drug is not worse than that of another drug by more than a specified margin.
d Time in therapeutic range (TTR): the percentage of time when a person has an INR within the prescribed range, when stroke and bleeding risk is lowest. For people with non-valvular AF this is 2–3.
e In the ARISTOTLE trial, bleeding outcomes were assessed in patients who received at least one dose of the study drug and events that occurred from the time the patients received the first dose of the study drug through 2 days after they received the last dose.
Table 5: Newer oral anticolagulants compared with warfarin31,32,36,f
||Intracranial haemorrhage: number needed to treat
||Major gastrointestinal bleed: number needed to harm
|Dabigatran 150 mg||228
|Dabigatran 110 mg
f Number needed to treat to prevent one intracranial haemorrhage or number needed to harm to cause one extra major gastrointestinal bleed in 1 year by using newer oral anticoagulants compared with warfarin.
g Differences in events compared with warfarin non-significant.