Gurmeen Kaur, MBBS
@kaurgurmeen
The approval of NOACs for stroke prevention in atrial fibrillation has revamped the way anticoagulation is managed. NOACS have practically replaced the use of warfarin for non valvular atrial fibrillation. Currently, 4 NOACs are approved: apixaban, dabigatran, rivaroxaban and edoxaban. Among those, apixaban is the most widely used NOAC in the United States at this time.
For this systematic analysis, all observational studies with use of apixaban, comparison with other NOACS or warfarin with at least 100 patients and 3 month follow up data were selected. The systematic review and meta-analysis were performed according to PRISMA recommendations. A literature search was performed using PubMed and Scopus databases up to 6 March, 2017.
A total of 9680 results were evaluated, and after review, 16 of the 173 studies screened were actually included. Studies ranged from 2015–2017. Eight studies were based in Europe, while 6 studies were based in United States, 1 study was based in the Middle-East, and 1 study in Japan. Mean/median age was consistent among most of the studies, ranging from 70 to 76 years. 4 of the 16 studies included people with a high thrombogenic risk with a CHA2 DS2 -VASc score ≥4.
In 15 of the 16 studies comparing apixaban with warfarin, apixaban was associated with a lower risk for stroke and systemic embolic events, as well as for major bleeding, particularly intracranial hemorrhage. Overall, the studies that compared apixaban with dabigatran and rivaroxaban found that apixaban was broadly comparable with dabigatran in terms of stroke/systemic embolic events with unclear differences compared with rivaroxaban. Apixaban was associated with lower major bleeding events and lower GI bleeding, independent of patient age.
Compared with warfarin, major bleeding risk was significantly lower for patients treated with apixaban (OR, 0.62; 95% CI, 0.51–0.75), with consistency for regular and low dose subgroups. Overall bleeding risk was lower, especially that of ICH. While there was no difference in thromboembolic event rates in apixaban versus dabigatran, major bleeding complications were lower with apixaban. Rivoraxaban had higher strokes and thromboembolic events, as well as higher rates of major bleeding.
The absolute risk reduction and the number needed to treat in this systemic analysis was very similar to the data from the ARISTOTLE trial. The meta-analysis, overall, demonstrated that use of apixaban in real life is associated with an overall nonsignificant difference in stroke and any thromboembolic events when compared with warfarin. There is an increasing body of evidence suggesting that patients on a lower dose of apixaban, i.e. 2.5 mg BID, are undertreated and associated with worse outcomes.
A better safety profile was demonstrated when comparing apixaban use to warfarin, dabigatran, or rivaroxaban. Apixaban is especially efficacious in reducing the rates of ICH and overall gastrointestinal bleeding. There are obviously limitations to an observational meta-analysis, but overall, based on the current evidence, apixaban seems to be a safe NOAC for use in anticoagulation for stroke prevention.
Figure: Number needed-to-treat comparison between real-world studies and ARISTOTLE trial.
