Real-world analyses show similar or better effectiveness and safety of NOACs compared to warfarin

Yao X, Abraham NS, Sangaralingham LR, et al.
J Am Heart Assoc 2016 doi:10.1161/JAH.116.003725

Background

Atrial fibrillation (AF) is associated with a 3- to 5-fold increased risk of stroke [1]. Non-Vitamin K oral anticoagulants (NOACs) can reduce this risk and demonstrated at least equivalent efficacy compared to warfarin in large phase III clinical trials [2-4].

However the efficacy and safety observed in clinical trials may not necessarily translate to routine practice because of the differences in patient populations, the intensity of follow-up and the variations in care that patients receive. Furthermore, because anticoagulants are long-term preventive medications without serious ongoing symptoms, adherence is substantially lower in observational studies than in clinical trials [5-8].

Several observational studies have been performed comparing warfarin with dabigatran or rivaroxaban but only a few studies have been done with apixaban [8-11]. The longer of these medications now allows greater follow-up and better powered analyses.

Therefore, using a large patient population from a wide variety of health care settings, the stroke and bleeding outcomes were associated with dabigatran, rivaroxaban, and apixaban use by comparing each agent with warfarin. This retrospective analysis was done using administrative claims data from OptumLabs Data Warehouse (OLDW) in which 125,243 AF patients (age ≥18 yrs) who were anticoagulated between 2010 and 2015 (7698 on apixaban, 14,881 on dabigatran, 16,795 on rivaroxaban and 85,869 on warfarin). All results are based on 1:1 propensity score matching.

Main results

• At baseline, dabigatran patients were younger than apixaban and rivaroxaban patients, had lower risk of stroke or bleeding and included a larger percentage of warfarin-naïve patients.
• Compared to warfarin, apixaban was associated with a reduced risk of stroke or systemic embolism (S/SE) (HR 0.67; 95% CI: 0.46-0.98, P=0.04), which was mainly driven by the lower risk of haemorrhagic stroke (HR 0.35; 95% CI: 0.14-0.88, P=0.03).
• Compared to warfarin, dabigatran was associated with a similar risk of S/SE (HR 0.98; 95% CI: 0.70-1.26, P=0.98), as was rivaroxaban (HR 0.93; 95% CI: 0.72-1.19, P=0.56).
• Compared to warfarin, apixaban was associated with lower risks of major bleeding (HR 0.45; 95% CI: 0.34-0.59), intracranial bleeding (HR 0.24; 95% CI: 0.12-0.50) and gastrointestinal bleeding (HR 0.51; 95% CI: 0.37-0.70), all P<0.001.
• Compared to warfarin, dabigatran was associated with lower risk of major bleeding (HR 0.79; 95% CI: 0.67-0.94, P<0.01) and intracranial bleeding (HR 0.36; 95% CI: 0.23-0.56, P<0.001).
• Compared to warfarin, rivaroxaban was associated with a lower risk of intracranial bleeding (HR 0.51; 95% CI: 0.35-0.75, P<0.001) but a higher risk of gastrointestinal bleeding (HR 1.21; 95% CI: 1.02-1.43, P=0.03).
• Subgroup analyses of dabigatran-warfarin showed a lower risk of major bleedings in dabigatran-treated patients with a CHA₂DS₂VASc score 2 or 3 (HR 0.46; 95% CI: 0.32-0.65, P<0.001) and in dabigatran-treated patients who were naïve for warfarin (HR 0.63; 95% CI: 0.50-0.79, P<0.01).
• Subgroup analyses of rivaroxaban-warfarin showed an elevated risk S/SE and major bleedings in rivaroxaban-treated patients with prior warfarin-experience (HR 1.63, 95% CI: 1.01-2.62, P<0.01 and HR 1.48, 95% CI: 1.12-1.95, P<0.01, respectively).

Conclusion

In these real-world effectiveness and safety analyses, apixaban was associated with better effectiveness and safety, dabigatran was associated with similar effectiveness but better safety, whereas rivaroxaban was associated with similar outcomes for both effectiveness and safety, when compared to warfarin.  

Find this article online at JAHA

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