"Idarucizumab for Dabigatran Reversal"
The New England Journal of Medicine. 2015.
PubMed • Full text • PDF

Contents

1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcome
8.2 Secondary Outcomes
9 Criticisms
10 Funding
11 Further Reading

Clinical Question

In patients treated with dabigatran who had serious bleeding or required an urgent procedure, does Idarucizumab reverse the anticoagulant effects of dabigatran?

Bottom Line

Idarucizumab rapidly and completely reversed the anticoagulant effects of dabigatran within minutes in the majority of patients and was found to be safe.

Major Points

Dabigatran is an oral anticoagulant used for stroke prevention in atrial fibrillation and venous thromboembolism. Serious bleeding events can occur, and there may be a need for urgent reversal, such as before surgery. Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effects of dabigatran. This prospective cohort study demonstrated that Idarucizumab effectively and rapidly reversed the anticoagulant effect of dabigatran.

Guidelines

As of 2015, there are no specific guidelines that reflect the results of this trial.

Design

Prospective cohort study, ongoing, multicenter

N=90 patients treated with dabigatran experiencing serious bleeding or requiring urgent procedures

Interventions included receiving 5g of intravenous Idarucizumab

Mean follow-up: at least 1 month, up to 90 days or until death

Primary Efficacy Outcome: Maximum percentage reversal of the anticoagulant effect of dabigatran
Primary Safety Outcome: Adverse events including thrombotic events and serious adverse events

Population

Inclusion Criteria: Adults ≥18 years of age taking dabigatran with overt, uncontrollable bleeding (Group A) or who required surgery or other invasive procedures (Group B)

Exclusion Criteria: None reported.

Baseline Characteristics: Majority were receiving dabigatran for atrial fibrillation; median age was 76.5 years; median creatinine clearance was 58 mL/min

Interventions

All patients received 5 g of intravenous idarucizumab

Outcomes

Primary Outcome: Among the patients with an elevated dilute thrombin time or ecarin clotting time at baseline, the median maximum percentage reversal was 100%, with reversal evident within minutes.

Secondary Outcomes: Hemostasis was restored in a median of 11.4 hours among bleeding patients (Group A) and normal intraoperative hemostasis was reported in 92% of patients undergoing procedures (Group B). One thrombotic event occurred within 72 hours after idarucizumab administration; 18 deaths overall were reported.

Criticisms

There was a lack of a control group, as it was deemed unethical to randomly assign patients to receive placebo or no active treatment. Therefore, the cohort design was selected.

Funding

This study was funded by Boehringer Ingelheim, the developer of Idarucizumab.

Further Reading for the full text and supplementary material of the article are available at NEJM.org.