Apixaban safest among DOACs vs warfarin, but tied to risk of all-cause mortality
Compared with warfarin, apixaban appears to be the safest drug among direct oral anticoagulants (DOACs), with decreased risks of major, intracranial and gastrointestinal bleeding, suggests a study. However, low-dose apixaban and rivaroxaban are associated with increased risks of all-cause mortality compared with warfarin.
“This large observational study, based on a general population in a primary care setting, provides reassurance about the safety of DOACs as an alternative to warfarin across all new incident users,” researchers said. “Our results give an initial, reassuring indication of the risk patterns for all patients taking anticoagulants, with respect to those prescribed apixaban.”
Apixaban, compared with warfarin, correlated with a reduced risk of major bleeding (adjusted hazard ratio [aHR], 0.66; 95 percent CI, 0.54–0.79) and intracranial bleeding (aHR, 0.40; 0.25–0.64) in patients with atrial fibrillation (AF), while dabigatran correlated with a lower risk of intracranial bleeding (aHR, 0.45; 0.26–0.77). Moreover, patients taking rivaroxaban (aHR, 1.19; 1.09–1.29) or low-dose apixaban (aHR, 1.27; 1.12–1.45) were seen to have an elevated risk of all-cause mortality. [BMJ 2018;362:k2505]
In patients without AF, apixaban led to a reduced risk of major bleeding (aHR, 0.60; 0.46–0.79), any gastrointestinal bleeding (aHR, 0.55; 0.37–0.83) and upper gastrointestinal bleeding (aHR, 0.55; 0.36–0.83) compared with warfarin, while rivaroxaban resulted in a decreased risk of intracranial bleeding (aHR, 0.54; 0.35–0.82). Patients on rivaroxaban (aHR, 1.51; 1.38–1.66) or low-dose apixaban (aHR, 1.34; 1.13–1.58) had an increased risk of all-cause mortality.
A previous meta-analysis shows comparable risks for bleeding, ischaemic stroke or systemic embolism and death in patients with AF or without valvular heart disease taking DOACs vs warfarin. For major bleeding, results of the present study support those from randomized controlled trials. [Health Technol Assess 2017;21:1-386; J Am Heart Assoc 2017;6:e005835]
“Apixaban appeared to be associated with the lowest risk of major bleeding in most of the larger studies. The risk of mortality in our subcohort with AF was similar for warfarin, dabigatran and apixaban but elevated for rivaroxaban,” according to researchers. [Gastroenterology 2017;152:1014-22.e1; Curr Med Res Opin 2017;33:1595-1604; BMJ 2016;353:i3189; Thromb Haemost 2017;117:1072-1082; JAMA Cardiol 2017;2:872-881]
“Like the Danish study, our risk of mortality in this subcohort was elevated only for patients on lower doses of apixaban and rivaroxaban. The other Danish study of standard dosage showed decreased mortality for apixaban, but our findings showed equivalent risk to warfarin for such patients,” they added. [BMJ 2016;353:i3189; BMJ 2017;356:j510]
The present prospective open cohort study included 132,231 warfarin, 7,744 dabigatran, 37,863 rivaroxaban and 18,223 apixaban users without anticoagulant prescriptions for 12 months prior to study entry. Participants were subdivided into 103,270 patients with AF and 92,791 without AF between 2011 and 2016.
“Anticoagulants are prescribed for a wide range of indications, although the adverse events have been studied mostly in patients with AF,” researchers noted.