The Responsible Use of Xarelto^®

Anticoagulation is undoubtedly associated with decreased morbidity and mortality from venous thromboembolism (VTE) and stroke in patients with atrial fibrillation.¹ However, all anticoagulants may cause unwanted bleeding. Achieving a balance between sufficient

anticoagulation to prevent blood from clotting while avoiding bleeding complications remains a constant challenge.

This article looks at the responsible use of anticoagulants, including Xarelto^® (rivaroxaban) a new oral anticoagulant (NOAC),

with practical guidance on how to take proactive steps to help avoid unforeseen haemorrhagic events and recognise specific patient groups that may warrant greater care than others when prescribed anticoagulation. ►

Bleeding – A Universal Problem

Haemorrhagic complications of anticoagulation are a universal phenomenon^2–4 associated with all the anticoagulants in clinical use today – from injected agents such as unfractionated heparin (UFH)⁵ and low molecular weight heparins (LMWHs)^6–8 through to oral agents such as warfarin⁹ and

NOACs, such as dabigatran,¹⁰ apixaban,¹¹ and Xarelto^®.¹²

Walking the Line With
Warfarin

The fine balance between providing effective anticoagulation and the risk of haemorrhage is particularly noticeable with older oral

anticoagulants such as the vitamin K antagonist (VKA) warfarin – which has a notoriously narrow therapeutic window.³

When using warfarin, the aim is to keep the Internationalised Normalised Ratio (INR) within a range of 2–3. However, this is often difficult because of differences between individuals in the way they metabolise the VKA (e.g., fast vs. slow metabolisers) and because of the multiple drug- and food-drug interactions associated with warfarin’s use. Consequently, even with routine INR monitoring and careful patient assessment, the risk of bleeding attributable to warfarin therapy remains substantial.²

In contrast, there is no need for routine coagulation monitoring of NOACs due to their more predictable pharmacokinetic ►

and pharmacodynamic profiles. Indeed, the benefits of anticoagulation can be consistently achieved with NOACs because of their fast onset of action (maximum blood concentrations are reached within a few hours of administration) and relatively short-half lives.^10–12

What is Responsible Anticoagulation Use?

Responsible use of anticoagulation involves ensuring that patients who are in need of anticoagulant therapy receive the most appropriate treatment. At the same time, responsible use involves being aware of the potential risks associated with such treatment, and taking preventative measures to avoid any unforeseen bleeding events both before and after therapy is initiated.

Specific groups of patients may require greater care than others when giving anticoagulation as they may be at greater risk of bleeding. Warfarin, for example, is associated with a number of drug- and food-drug interactions that can increase the complexity of anticoagulation with this agent. Indeed, patients taking warfarin should ideally limit the intake of green leafy vegetables containing high levels of vitamin K (e.g., kale, spinach and broccoli). Patients should also be forewarned to ask before taking any dietary supplements or other over-the-counter medicines that could interfere with warfarin’s metabolism and thus alter the bleeding risk.

Other factors that can influence whether or not bleeding will occur include: ^2,13

• Patient Age
  Older patients may be at greater risk of bleeding than younger patients due to various reasons.
• Concomitant Disease
  Co-existing medical problems, such as liver or renal impairment, can increase the risk of haemorrhage.
• Alcohol Intake
  Heavy alcohol use can increase the risk of bleeding complications with some anticoagulants.
• Adherence
  Patients need to understand the benefits and risks of treatment, and understand why adherence is vital to achieving and maintaining effective anticoagulation and thus stay ►

protected against stroke in atrial fibrillation and VTE.

Responsible Use of Xarelto^®

Xarelto^® offers a number of benefits compared to other anticoagulants which may help to overcome certain limitations of anticoagulation treatment. These benefits include:

• Consistent safety and efficacy results in a large number of phase III clinical trials
• Predictable pharmacokinetic and pharmacodynamic properties
• No coagulation monitoring
• Once-daily, oral administration of a single pill*

Nevertheless, the treatment benefits of Xarelto^® and the

possible risk of bleeding should be assessed and balanced against each other before starting therapy.

Certain groups of patients might be at a higher risk of bleeding when taking Xarelto^® than others and may therefore require additional care and attention while being treated.†

• Patients with Renal Impairment
  Patients with moderate (creatinine clearance [CrCl] 30–49 ml/min) or severe (CrCl 15–29 ml/min) renal impairment may receive a reduced dose. See “dosing recommendations” in the Prescriber Guide.

Xarelto^® is not recommended for use in patients with CrCl <15 ml/ min. ►

• Patients with Hepatic Impairment
  Xarelto^® is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including cirrhotic patients with Child Pugh B and C.
• Patients Concomitantly Receiving Certain Other Drugs
  Systemic azole-antimycotics (e.g. ketoconazole, itraconazole, voriconazole and posaconazole) or HIV protease inhibitors (e.g. ritonavir): use of Xarelto^® is not recommended. When taking drugs affecting haemostasis such as nonsteroidal anti- inflammatory drugs, acetylsalicylic acid, platelet aggregation inhibitors or other antithrombotic agents,

care should be taken and patients should be monitored for potential bleeding.

• Patients with Other Haemorrhagic Risk Factors
  • Uncontrolled severe arterial hypertension
  • Active ulcerative gastrointestinal disease
  • Recent gastrointestinal ulcerations
  • Vascular retinopathy
  • Recent intracranial or intracerebral haemorrhage
  • Intraspinal or intracerebral vascular abnormalities
  • Recent brain, spinal or ophthalmological surgery
  • Bronchiectasis or history of pulmonary bleeding

Treatment in these patient groups needs to be undertaken with appropriate caution and only after full assessment of the potential ►

benefits of therapy versus the risk of bleeding.

What do Patients Need to Know?

Patients need to be made aware of the benefits as well as the risks of anticoagulation in general and more specifically about the anticoagulant being used (e.g. Xarelto^®). For instance,

patients should know how to react in certain situations that might increase their individual risk of bleeding and learn to recognise the signs and symptoms of bleeding while on anticoagulation.

All patients treated with Xarelto^® should be given the Xarelto^® Patient Card which covers topics of importance for patients, including how to detect signs or symptoms of bleeding.

Ensuring Anticoagulation is given Responsibly

In summary, the responsible use of anticoagulants involves:

• Helping patients understand the importance and benefits of continued anticoagulation;
• Recognising all anticoagulant agents carry the risk of bleeding to some extent;
• Appropriate use in ‘at-risk’ patient groups;
• Educating patients to recognise bleeding signs and symptoms.

Such an approach will help to ensure that patients are able to obtain the optimum benefit from their anticoagulant treatment.