Specific Reversal Agents for Direct Oral Anticoagulants in Acute Stroke

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Acute intracranial haemorrhage associated with FXa inhibitor use (n=530). Intervention: Andexanet alfa vs. Usual care. Primary outcome: Effective haemostasis at 12 hours (ARR 13.4%, 95% CI 4.6%, 22.2%, p=0.0032).

Senta Frol; Janja Pretnar Oblak; Mišo Šabović; Wim H. van Zwam; George Ntaios; Karl‐Olof Lövblad; Andreas Gruber; Pawel Kermer

doi:10.1177/10760296241279545

January 1, 2024Clinical and Applied Thrombosis/HemostasisOpen Access

Specific Reversal Agents for Direct Oral Anticoagulants in Acute Stroke

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Why the study?

With the increasing use of DOACs and the need for mandatory anticoagulation reversal before procedures in acute stroke, an evaluation of the advantages and concerns of specific reversal agents in everyday clinical practice was needed.

Does andexanet alfa reverse anticoagulation and improve haemostasis in patients with major bleeding on factor Xa inhibitors?

Study Design

Type

RCT (n=530)

Blinding

Open-label

Randomization

1:1

Structured PICO

Does andexanet alfa reverse anticoagulation and improve haemostasis in patients with major bleeding on factor Xa inhibitors?

P

Population

530 patients (median age 80 years, 47.7% female) presenting with acute intracranial hemorrhage within 15 hours of taking an oral FXa inhibitor.

I

Intervention

Andexanet alfa administered as an intravenous bolus (400 mg low dose or 800 mg high dose at 30 mg/min) followed by a continuous infusion (4 mg/min or 8 mg/min) for 120 minutes.

C

Comparator

Placebo (in healthy volunteer studies) or usual care (in ANNEXA-I study, where 87.6% received prothrombin complex concentrate).

O

Outcome

Percent change in anti-FXa activity from baseline to nadir, and rate of effective haemostasis (defined in ANNEXA-I as a composite of ≤ 35% increase in haematoma volume, < 7-point change in NIHSS score, and no rescue therapies within 3 to 12 hours).composite

Main Result

Absolute Risk Reduction: 13.4 (95% CI 4.6–22.2)

Absolute Event Rate: 67% vs 53.1%

Absolute Risk Reduction: 13.4%

p-value: p=0.0032

Andexanet alfa effectively reverses anti-FXa activity and achieves haemostasis in patients with acute major bleeding on apixaban or rivaroxaban, though it carries a risk of thromboembolic events.

Limitations

Open-label study design
Higher rate of thrombotic events in patients with prior history of stroke, myocardial infarction, or heart failure
Clinical benefit in terms of reduced morbidity or mortality has not been demonstrated
Commercial anti-FXa-activity assays are unsuitable for measuring anti-FXa activity following administration
Clinical benefit in terms of reduced morbidity or mortality has not been demonstrated.
Data from bleeding patients are limited and validation has not been successful yet.
Treatment of patients with more severe ICrH (GCS ≤ 7 or haematoma volume > 60 mL) has not been studied.
Commercial anti-FXa-activity assays are unsuitable for measuring anti-FXa activity following administration.

Implication

Highlights need for individualized reversal strategies in DOAC stroke; leaves open consensus on agent selection and timing.

Abstract

Direct oral anticoagulants (DOACs) changed stroke prevention and decreased the risk of ischemic and hemorrhagic complications in patients on oral anticoagulation (OAC) therapy. The numbers of patients prescribed DOACs has increased rapidly. Availability of specific reversal agents opened new avenues in the prevention and management of DOAC complications. An ideal specific reversal agent for a DOAC in acute stroke is an agent which lacks safety concerns and immediately reverses DOAC anticoagulation activity, thereby enabling effective treatment. Reversal of anticoagulant activity is mandatory in patients with acute ischemic stroke (AIS) before performing therapeutic procedures such as intravenous thrombolysis (IVT) and neurosurgery in intracranial hemorrhage (ICH) in order to improve clinical outcomes. In this manuscript we pursue an interdisciplinary approach in discussing advantages and concerns of specific reversal agents in acute stroke DOAC-treated patients in everyday clinical practice.

Discussion

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Cite This Study

Frol et al. (2024) conducted an RCT in Acute intracranial haemorrhage associated with FXa inhibitor use (n=530). Andexanet alfa vs. Usual care was evaluated on Effective haemostasis at 12 hours (ARR 13.4%, 95% CI 4.6%, 22.2%, p=0.0032).

synapsesocial.com/papers/6a786fa9d8eb58afc2be88ec https://doi.org/10.1177/10760296241279545

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Ask AI

Bookmark

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Specific Reversal Agents for Direct Oral Anticoagulants in Acute Stroke

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Specific Reversal Agents for Direct Oral Anticoagulants in Acute Stroke

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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