Long-term anticoagulation is required to prevent stroke in patients with atrial fibrillation, to prevent venous thromboembolism (VTE) after orthopaedic surgery, and for the acute and continued treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE).

There are several new oral anticoagulant NOACs that offer patients and clinicians an alternative choice to the traditional methods used. In this article, the practical use of one of these, Xarelto^®, is highlighted with a focus on how to convert from vitamin K antagonists (VKAs) and other anticoagulants such as low-molecular-weight heparins (LMWHs) to Xarelto^® and vice versa.

Factors Determining Anticoagulant Use

The choice of anticoagulant depends upon a variety of factors including the individual circumstances of the patient and clinical experience. Two factors that may influence a decision to change from one anticoagulant to another are:

• the overall convenience of the anticoagulant therapy and the ease of administration for the patient
• the balance between the risks and the benefits of the different anticoagulants concerned.

Until recently VKAs were the only oral anticoagulants available for patients requiring long-

term anticoagulation to prevent stroke in atrial fibrillation (SPAF), LMWH for VTE prevention, and LMWH followed by VKA for DVT treatment and the continuous treatment of recurrent DVT and PE.

Today, while there are several new oral anticoagulants that have been tested in clinical trials, there is only one – Xarelto^® – that is approved for SPAF, VTE prevention, and the treatment of acute DVT and long-term prevention of recurrent events.¹

Converting from VKAs

Once a decision to convert a patient to Xarelto^® has been made then the process required depends upon the current anticoagulant being used. Whatever anticoagulant is being used, it is important to ensure continuous anticoagulation in every clinical ►

setting while conversion takes place. If a patient is currently taking a VKA such as warfarin then it is particularly important to ensure that any risk of bleeding is minimised by proactive management of the patient while the anticoagulation regimen is altered.

After stopping treatment with the VKA, Xarelto^® can be started once the INR of the patient has reached the appropriate threshold. This threshold depends on the indication (Figure 1).

• For SPAF, Xarelto^® should be initiated only when INR is <3.0.

• For DVT treatment and for the continuous treatment of recurrent DVT and PE, Xarelto^® should be initiated only when the INR is <2.5.

INR monitoring is no longer required once the conversion to Xarelto^® has been completed. INR values will be falsely elevated after the initial dose of Xarelto^®.

Converting from Xarelto^® to VKAs

If conversion back to a VKA from Xarelto^® is planned, overlapping treatment with Xarelto^® and the VKA is required initially to ensure appropriate anticoagulation. Xarelto^® can be stopped once the INR is above a threshold of 2.0. In this case, INR monitoring should only be performed 24 hours after the last dose of Xarelto^® and before the next dose is due¹.►

This recommended procedure ensures that Xarelto^® has no influence on the INR values. (Figure 2)

Converting from and to a Parenteral Anticoagulant

For patients currently receiving a parenteral anticoagulant, such as unfractionated heparin (UFH) or a low-molecular-weight heparin (LMWH), the following recommendation applies.

• UFH
  Xarelto^® should be started at the time of discontinuation of the continuously administered parenteral medicinal product.

• LMWH
  Xarelto^® should be started 0–2 hours before the time of the next scheduled administration of LMWH.

If conversion back to a parenteral anticoagulant is required, Xarelto^® should be stopped and the first dose of UFH/LMWH given at the time when the next dose of Xarelto^® would have been taken.

Anticoagulant Monitoring

When using Xarelto^®, routine coagulation monitoring is not required. As a factor Xa inhibitor, standard coagulation tests such as the prothrombin time (PT) and the activated partial thromboplastin time (aPTT) may be altered after administration of Xarelto^® and so these are not reliable measures of its anticoagulant activity.►

In particular, the International Normalised Ratio (INR) is an unsuitable measure to monitor the anticoagulant effect of Xarelto^® and FXa inhibition.

INR testing was specifically developed for measuring the anticoagulant effects of VKAs, and so is not appropriate to use it to gauge the effects of newer oral anticoagulants.

If clinically indicated, a patient’s haemostatic status can be assessed by measuring the PT

using neoplastine as the only reagent, and as described in the Xarelto^® Summary of Product Characteristics.¹ Anti-FXa chromogenic assays have also been developed and are available commercially.

Why Convert to Xarelto^®?

Xarelto^® enables a single-drug approach versus LMWH plus VKA for the initial and continued treatment of DVT. It also provides a convenient once- daily dosing option for the long- term prevention of VTE.

Xarelto^® also offers a single drug approach for SPAF. In all clinical situations, there is no need for routine coagulation monitoring with Xarelto^®.

For detailed information on how to convert a patient from another

anticoagulant to Xarelto^®, please refer to the Summary of Product Characteristics.

The Prescriber Aid also summarises how to convert from a VKA or parenteral anticoagulant Xarelto^® and vice versa and provides further practical guidance.