Adherence to protocols for the use of reversal agents in patients treated with direct oral anticoagulants

Abstract

Objectives

This study aimed to evaluate the adherence to protocols for the use of reversal agents in direct oral anticoagulant (DOAC) users in Dutch hospitals.

Methods

A retrospective cohort study was conducted in seven hospitals in the Netherlands. Treatment protocols for bleeding and (urgent) procedures in patients on DOAC were collected from each hospital. All patient data on the use of reversal agents were retrospectively collected from September 2021 to April 2022 and compared to the protocols. The degree of per-protocol adherence (compliance score) was categorized into four levels as follows: poor (<45%), moderate (45–79%), high (80–89%), and full (> 90%) adherence rates.

Results

A total of 290 patients were included in our study. In patients with bleeding under DOAC, the protocol adherence for prothrombin complex concentrate (PCC) was “moderate” (61%). In the remaining cases (39%), non-adherence was mainly caused by underdosing (68%), overdosing (12%), and a lack of indication (14%). Furthermore, idarucizumab was administered for bleeding with “full” adherence (96%). For andexanet alfa, adherence to the hospital bleeding protocol was “moderate” (67%), with a lack of indication being the only reason for non-adherence. In case of reversal for an urgent procedure, the protocol adherence for PCC was “low” (45%), with underdosing, a lack of indication, and missing lab data being the main reasons for non-adherence. Missing lab data on dabigatran plasma concentration before reversal was the main reason for “low” adherence (26%) in idarucizumab. The adherence for andexanet alfa was also “low” (0%).

Conclusion

In case of reversal for bleeding under DOAC, overall adherence to the protocol was “moderate”; however, in patients needing an urgent procedure, it was “low.” The major reasons for non-adherence were underdosing, off-label use, and a lack of specific lab testing. The results of this study can assist in improving the implementation of hospital protocols.

Keywords:

• DOAC
• bleeding
• intervention
• adherence
• protocol
• reversal

Transparency

Declaration of funding

There is no funding to disclose.

Declaration of financial/other relationships

K.M reports speaker fees from Alexion, Bayer, and CSL Behring, participation in the trial steering committee for Bayer, consulting fees from Uniqure, participation in the data monitoring and endpoint adjudication committee for Octapharma. All fees are paid to her institution. D.M, M.v.E, L.V, N.v.R, P.v.d.B, M.v.H, A.R, H.L, N.V, and E.v.R declare no conflicts of interest. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

M.v.E, A.R, and N.v.R gathered data; D.M, N.V, and E.v.R designed and initiated the research; M.v.E analyzed protocols and performed statistical analysis; D.M, N.V, M.v.E, and E.v.R analyzed the results; D.M, L.V, P.v.d.B, M.v.H, H.L, K.M, N.V, and E.v.R contributed to writing or reviewed this this article.

Acknowledgements

None reported.