Restart of Anticoagulant Therapy and Risk of Thrombosis, Rebleeding, and Death after Factor Xa Inhibitor Reversal in Major Bleeding Patients.

Abstract

BACKGROUND:

Lack of data on balancing bleeding and thrombosis risk causes uncertainty about restarting anticoagulants after major bleeding. Anticoagulant reversal trials offer prospectively gathered data after major bleeding with well-documented safety events and restarting behavior.

OBJECTIVES:

To examine the relationship of restarting anticoagulation with thrombosis, rebleeding, and death.

METHODS:

This is a posthoc analysis of a prospective factor Xa inhibitor reversal study at 63 centers in North America and Europe. We compared outcomes of restarted patients with those not restarted using landmark and time-dependent Cox proportional hazards models. Outcomes included thrombotic and bleeding events and death and a composite of all three.

RESULTS:

Of 352 patients enrolled, oral anticoagulation was restarted in 100 (28%) during 30-day follow-up. Thirty-four (9.7%) had thrombotic events, 15 (4.3%) had bleeding events (after day 3), and 49 (14%) died. In the landmark analysis comparing patients restarted within 14 days to those not, restarting was associated with decreased thrombotic events (hazard ratio [HR] = 0.112; 95% confidence interval [CI]: 0.001-0.944; p = 0.043) and increased rebleeding (HR = 8.39; 95% CI: 1.13-62.29; p = 0.037). The time-dependent Cox model showed evidence for a reduction in a composite (thrombotic events, bleeding, and death) attempting to capture net benefit (HR = 0.384; 95% CI: 0.161-0.915; p = 0.031).

CONCLUSION:

This analysis provides modest evidence that restarting anticoagulation in factor Xa inhibitor-associated major bleeding patients is correlated with reduced risk of thrombotic events and increased risk of rebleeding. There is low-level evidence of net benefit for restarting. A randomized trial of restarting would be appropriate.

• Authors: Truman J Milling Jr, Ben King, Patrick Yue, Saskia Middeldorp, Jan Beyer-Westendorf, John W Eikelboom, Mark Crowther, Lizhen Xu, Peter Verhamme, Deborah M Siegal, Stuart J Connolly, ANNEXA-4 Investigators
• Journal: Thrombosis and haemostasis (Thromb Haemost) Vol. 121 Issue 8 Pg. 1097-1106 (08 2021) ISSN: 2567-689X [Electronic] Germany
• PMID: 33634446 (Publication Type: Journal Article, Multicenter Study)
• Copyright: The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Chemical References

• Anticoagulant Reversal Agents
• Factor Xa Inhibitors
• PRT064445
• Recombinant Proteins
• Factor Xa

Topics

• Aged
• Aged, 80 and over
• Anticoagulant Reversal Agents (adverse effects, therapeutic use)
• Anticoagulation Reversal (adverse effects, mortality)
• Drug Administration Schedule
• Europe
• Factor Xa (administration & dosage, adverse effects)
• Factor Xa Inhibitors (administration & dosage, adverse effects)
• Female
• Hemorrhage (chemically induced, drug therapy)
• Humans
• Male
• North America
• Prospective Studies
• Recombinant Proteins (administration & dosage, adverse effects)
• Recurrence
• Risk Assessment
• Risk Factors
• Thrombosis (diagnosis, mortality, prevention & control)
• Time Factors
• Treatment Outcome