Periprocedural Direct Oral Anticoagulant Management

Study Overview
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Brief Summary
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Direct oral anticoagulants (DOAC) are a new drug group that has been approved for chronic anticoagulation of patients in atrial fibrillation or suffering acute thrombosis, between others. The need of surgery of a patient in atrial fibrillation is round 10% per year. Due to DOAC short time of commercialization and the lack of experience, the proper management of DOAC when a patient in this treatment needs a scheduled or urgent procedure, has not yet been established. This fact may mean both the decrease of the anticoagulant treatment efficacy and the increase of the haemorrhage complications in the perioperative period. With the aim of gaining additional information about this aspect, a multicentre, prospective and observational study (classified by the spanish drug society, AEMPS, as non-interventional trial, EPA-SP) about the DOAC management, before a scheduled or urgent surgery, in normal clinical practice, is proposed.

Detailed Description
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When an anticoagulated patient is scheduled for surgery or an invasive procedure, the physician's worry is how to achieve needing an optimal haemostasis without increasing the risk of thrombosis. For decades, the main drug for chronic anticoagulation has been antivitamin-k (warfarin or acenocoumarol). In the majority of patients, the periprocedural management proposal has been stopping the drug and giving a short acting anticoagulant for some days before surgery, known as bridging therapy strategy, mostly done with a low-molecular weight heparin (LMWH). The debate about the best perioperative management of the anticoagulated patients has increased with the arrival on the market of direct oral anticoagulants (DOAC), by the moment approved for long-term anticoagulation in patients with atrial fibrillation and for the treatment of pulmonary embolism. DOAC could be classified in two groups: direct inhibitors of thrombin (the only current available drug is dabigatran) and direct inhibitors of factor Xa (rivaroxaban, apixaban, edoxaban, and others soon to come). DOAC have pharmacokinetic characteristics that seem to favour stopping the drug for some days without substitution in the vast majority of the patients. Nevertheless, current lack of experience in the management of high doses of DOAC during the perioperative period, the absence of effective antagonists to reverse the anticoagulation, the unsuitable standardized laboratory monitoring and, also, the different pharmacokinetics between patients receiving these drugs, have made challenging to standardize the optimal management in the perioperative period. Some proposals have been published in last years from expert consensus, based on pharmacokinetic data, but DOAC short time of commercialization and the difficulties to interpret the post-hoc analysis from the randomized trials, for the heterogeneity of the included population and the wide kind of surgeries, most of them with low bleeding risk, have moved the spanish working group on perioperative management of haemostasis to plan a multi-institutional registry to gain experience and information in the periprocedural (urgent or scheduled) management of DOAC. The authors designed an observational, prospective, multicentre study including patients under long-term DOAC treatment for atrial fibrillation or treatment of venous thromboembolism who are scheduled or need an urgent procedure. Data collected were demographic, related with the DOAC management and with the possible haemorrhagic or thrombotic events with a follow-up of 30 day. A univariable analysis and a multivariate regression model were applied using all the available co-variables. Bilateral hypothesis contrast were considered significant if α < 0.05.

Official Title
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Prospective Observational Study of the Direct Oral Anticoagulants Periprocedural Management

Conditions
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Periprocedural Complication

Intervention / Treatment
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* Drug: Direct oral anticoagulant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 18 years of age and older Under direct oral anticoagulant Urgent or scheduled surgery or invasive procedure needed Signed and dated informed consent form Exclusion Criteria: None

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Direct oral anticoagulant|Time of direct oral anticoagulant withdrawal Use or not of bridging with low molecular weight heparin|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Periprocedural thrombotic complications | Accumulative incidence rate of thrombotic events (cardiovascular, neurological, or venous thromboembolic event) | 1 month | 
| Periprocedural hemorrhagic complications | Accumulative incidence rate of minor and major bleeding events | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Outcome of bridging therapy | Relationship between the incidence of complications and the use of bridging therapy. | Between one week before and one month after procedural | 
| Knowing actual DOAC management in clinical practice | Composite of time of withdrawal of direct oral anticoagulant, use or not of low molecular weight heparin as bridge therapy, time of reintroduction of direct oral anticoagulant | Between one week before and one month after procedural | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Novel oral anticoagulant, Perioperative medicine, Periprocedural, Anticoagulation, Dabigatran, Rivaroxaban, Apixaban, Edoxaban, Direct oral anticoagulant, Surgery, Anaesthesia