Oral Factor Xa inhibitors (xabans) better prevent thromboembolic complications than warfarin in atrial fibrillation

SOURCE
Bruins Slot KMH, Berge E.  (2018) Factor Xa inhibitors versus vitamin K antagonists for preventing cerebral or systemic embolism in patients with atrial fibrillation. Cochrane Database Syst Rev 3 :CD008980.

CONTEXT
The introduction of factor Xa inhibitors (FXaI), including xabans and parinux, offers an alternative to vitamin K antagonist (VKA) in the management of non-valvular atrial fibrillation (AF). Non-valvular AF is common and its prevalence is expected to increase due to the ageing of the population.

CLINICAL QUESTION
Are FXaI as effective and well tolerated as VKA in the prevention of stroke and peripheral embolism in people with AF?

BOTTOM LINE
The composite primary outcome, all stroke and peripheral embolism, is significantly reduced in subjects taking FXaI compared to those taking VKA (high quality evidence). Major bleeding is also significantly reduced with high statistical heterogeneity (moderate quality evidence). The use of FXaI significantly and importantly reduces the occurrence of intracranial hemorrhages (high quality evidence) and, to a lesser extent, overall mortality (moderate quality evidence). Non-major clinically relevant bleedings are significantly reduced with FXaI but with high statistical heterogeneity. The class of anticoagulant does not influence the rate of myocardial infarction.

Sub-groups analyses:

  • Xabans significantly reduce the occurrence of peripheral strokes and embolism, while parinux (parenteral FXaI) does not have a significant effect on this composite outcome.
  • Xabans cause significantly less major bleeding compared to VKA, while parinux is associated with a higher risk of major bleeding.
  • In people over 75 years of age, FXaI significantly reduce the occurrence of strokes and peripheral embolism, while, regardless of age, FXaI causes less major bleedings.
  • Regardless of gender, the efficacy and tolerance of FXaI compared to VKA is similar.

Apixaban and rivaroxaban are the only 2 xabans that are superior to VKA on the primary outcome. Apixaban, betrixaban and edoxaban cause significantly less major bleeding compared to VKA.
In the subgroup of VKA subjects with median time-in-therapeutic range (TTR) > 60%, xabans are equal to warfarin on the primary outcome. In contrast, xabans are superior to warfarin with TTR < 60%.
In all cases, xabans cause less major bleeding. The reduction in the primary outcome with xabans is observed with or without associated antiplatelet therapy, and this without increased hemorrhagic risk compared to warfarin.
A significant reduction in the primary outcome with xabans was observed only for subjects with a CHADS2 score of 3 or more, while xabans were associated with less major bleeding regardless of the CHADS2 score.

CAVEAT
In this important meta-analysis (>67,000 patients) of randomized controlled trials, 90% of the data came from the comparison of 3 xabans (apixaban, edoxaban and rivaroxaban) with warfarin. The beneficial effect of xabans is mainly due to the reduction of hemorrhagic strokes since the efficacy of xabans, although significant, remains clinically very modest. The results of the subgroup analyses should be interpreted with caution due to incomplete data or significant statistical heterogeneity.

Finally, the median follow-up time varied considerably across studies, from 12 weeks to 2.8 years. The quality of life and a medico-economic analysis between FXaI and VKA were not evaluated in this study.

AUTHORS INFORMATION 

S. BEROUD
Service d’Accueil des urgences, Hospices civils de Lyon, CHU Lyon-Sud,
Lyon, France
sebastien.beroud@chu-lyon.fr

P. JABRE
Samu de Paris, CHU Necker–Enfants-Malades,
Paris, France
patricia.jabre@aphp.fr

K. MAGEE
Dalhousie University – QEII Health Science Centre
Nova Scotia, Canada
kirk.magee@dal.ca