Real-world persistence to direct oral anticoagulants in patients with atrial fibrillation: a systematic review and network meta-analysis

Abstract

Objective

To conduct a systematic review and network meta-analysis of real-world evidence comparing adherence, persistence, cost, and utilization between oral anticoagulant (OAC) in non-valvular atrial fibrillation (NVAF) patients.

Methods

A systematic search of MEDLINE and Embase (inception-July 2019) was conducted for published observational cohort studies comparing outcomes between ≥2 OACs. A network meta-analysis was performed to estimate odds ratios for non-persistence using a random-effects model.

Results

There were 80 studies evaluating the outcomes of interest. However, due to a paucity in adherence studies and heterogeneity in adherence, cost, and utilization definitions, persistence was the focus of this network meta-analysis. There were 36 studies evaluating non-persistence in 395,593 participants, 24 of which used 3 gap definitions (30-, 60-, and 90-days); 18 unique studies evaluating non-persistence at 12 months were included in the network meta-analysis. Using 30- and 90-day gaps, all NOACs, when compared with VKAs, had lower odds of non-persistence (30-day OR (95%CI): apixaban: 0.63 (0.58, 0.69); rivaroxaban: 0.69 (0.62, 0.76); dabigatran: 0.89 (0.82, 0.97); 90-day OR (95%CI): apixaban: 0.33 (0.22, 0.47); rivaroxaban: 0.47 (0.36, 0.61); dabigatran 0.61 (0.44, 0.85)). When using a 60-day gap, dabigatran had higher odds of non-persistence vs VKAs (OR: 1.35; 95%CI: 1.12, 1.61), but there were no significant differences for apixaban and rivaroxaban. Apixaban had the lowest probability of non-persistence across the 3-gap definitions (95.7% with 30-day gap, 76.9% with 60-day gap, 98.4% with 90-day gap).

Conclusions

The current findings, despite multiple limitations, can raise awareness and understanding of real-world persistence associated with OAC therapy in NVAF patients.

Keywords:

• Anticoagulants
• atrial fibrillation
• systematic review

Transparency

Declaration of funding

This work was supported by Pfizer Inc and Bristol-Myers Squibb Company.

Declaration of financial/other relationships

SD is a consultant for Bristol Myers Squibb Company/Pfizer Inc., Daiichi-Sankyo, Portola, and Boehringer Ingelheim, and has been on the speakers’ bureau for Janssen, Bristol Myers Squibb Company/Pfizer Inc., and Boehringer Ingelheim. MDF, MS, RM, and JCC are paid employees of Pfizer Inc. AKang is a paid employee of Bristol-Myers Squibb Company. AKeshishian and CG are paid employees of STATinMED Research which is a paid consultant, for the development of this manuscript, to Bristol-Myers Squibb Company and Pfizer Inc. Peer reviewers on this manuscript have received an honorarium from CMRO for their review work but have no other relevant financial relationships to disclose.

Acknowledgements

None stated.

Data availability statement

The data is available from the corresponding author at reasonable request.

Notes

i StataCorp, Release 15.1, College Station, Texas, USA.