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Indications for vitamin K antagonist therapy

Understanding when vitamin K antagonist therapy is beneficial for my patients.

While hemostasis is necessary for survival, the pathological formation of a blood clot, or thrombosis, poses significant health risks.

The main indications for a patient to receive vitamin K antagonists (VKAs) are the following:

  • Mechanical heart valves
  • Atrial fibrillation
  • Deep vein thrombosis and pulmonary embolism
  • Myocardial infarction
  • Acute ischemic stroke

 

Mechanical heart valves

 

Permanent anticoagulation therapy is justified by an increased risk of thromboembolic complications after replacement of any valve with a mechanical prosthesis.1,2 Most heart valve defects are acquired later in life and are due to degenerative heart valve disease. Heart valve replacement becomes necessary when hereditary or acquired defects severely limit valve function.

Main causes of heart valve disease:3
  • Congenital heart disease
  • Rheumatic fever 
  • Cardiomyopathy
  • Heart muscle damage due to heart attack
  • Aging
  • A previous infection with endocarditis 

 

Acquired valvular stenosis may be a consequence of organic changes to the tissue of the valve; insufficiency may be a secondary consequence of ventricle volume load or congestive heart failure.

Today, the indication for operation and/or interventional treatment of the heart valves is considered earlier.4 In Europe, corrective heart valve surgery is performed in approximately 25% of all heart operations: Mechanical heart valves are particularly long-lived, but require that the patient takes life-long oral anticoagulation medication.2 Biological heart valve prostheses have the benefit of not requiring prolonged anticoagulation, but calcify sooner and have to be replaced after 10 to 15 years,5 with an increased risk linked to the second valve replacement surgery.

 

Anticoagulation

 

Lifelong oral anticoagulation treatment using a VKA is recommended for all patients with a mechanical valve.6

According to the American College of Chest Physicians (ACCP) guidelines, the following is recommended for patients:7

  • In patients with a mechanical aortic valve, VKA therapy with a target INR of 2.5 (range 2.0-3.0) over lower targets (Grade 2C recommendation)
  • In patients with a mechanical aortic valve, VKA therapy with a target INR of 2.5 (range 2.0-3.0) over higher targets (Grade 1B recommendation)
  • In patients with a mechanical mitral valve, VKA therapy with a target of 3.0 (range 2.5-3.5) over lower INR targets (Grade 2C recommendation)
  • In patients with mechanical heart valves in both the aortic and mitral position, target INR 3.0 (range 2.5-3.5) over target INR 2.5 (range 2.0-3.0) (Grade 2C recommendation)

The American College of Cardiology (ACC)/American Heart Association (AHA)8 provide fairly similar recommendations regarding the use of anticoagulation. However, the target INR should be adapted to patient risk factors and the thrombogenicity of the prothesis.6

Post-operative mortality and morbidity can be improved through individual adjustment of anticoagulation intensity, involvement of the patient, and the use of the international normalized ratio (INR) as a control parameter. Studies such as ESCAT (Early Self Controlled Anticoagulation Trial)9,10 have shown that in cases where patients practice self-management they remain within their optimum therapeutic target range for a higher percentage of time and so significantly reduce the rate of complications. Recent guidelines from the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) also strongly support INR self-management provided appropriate training and quality control are performed (class I, level B recommendation)6

Non-vitamin K antagonist oral anticoagulant (NOAC) treatment is contraindicated in patients with a mechanical heart valve.11

 

Risk factors:

 

Atrial fibrillation, previous thromboembolism, left ventricular dysfunction, hypercoagulable conditions, older-generation thrombogenic valves, mechanical tricuspid valves, or more than 1 mechanical valve.8

 

Atrial fibrillation

 

Atrial fibrillation (AF) is the most common heart rhythm abnormality that people develop. During AF the heart's two upper chambers (the atria) beat chaotically and irregularly. The condition causes poor blood flow and the development of blood clots within the heart which can subsequently release into the arteries of the brain and cause a stroke. It is primarily a problem of the elderly.

 

AF is often classified as follows:
 
  • Recurrent AF: two or more episodes of AF
  • Paroxysmal AF: episodes end spontaneously within seven days
  • Persistent AF: pharmacologic or electrical cardio-version is required to terminate the arrhythmia
  • Permanent AF: sustained AF despite treatment to end the arrhythmia or when cardio version is inappropriate

 

Approximately 15%-20% of ischemic strokes occur in patients with AF.12 The attributable risk of stroke in AF patients increases significantly with age, rising from 1.5% for those aged 50-59 years to 23.5% for those aged 80-89 years.13 Indeed, elderly patients with AF are at the highest risk for stroke and the highest risk for hemorrhage.14 After adjusting for comorbid cardiovascular conditions, AF is associated with a 50% to 90% increase in mortality risk.15 Furthermore, stroke is a leading cause of serious long-term disability.16

AF is the most common arrhythmia worldwide and the estimated global age adjusted prevalence was 0.5% in 2010 - nearly 33.5 million individuals.17 During the last 20 years there has been a 66% increase in hospitalizations due to AF and emerging evidence has also indicated an association between AF and pulmonary embolism.18

 

Anticoagulation

 

Five landmark clinical trials - AFASAK, SPAF, BAATAF, CAFA, and SPINAF - have demonstrated the unequivocal benefits of the VKA, warfarin, in preventing stroke among patients with AF.19-23 

This was confirmed recently by the BAFTA study that showed stroke risk is significantly lowered by 64% with warfarin treatment compared to aspirin in an elderly population. The risk for major hemorrhage was reduced by 12% (although non-significant).24

Where oral anticoagulation is indicated, a risk stratification (e.g. using the CHA2DS2-VASc score) should be performed to estimate the risk of stroke in patients with nonvalvular AF.25 The CHA2DS2-VASc scoring system assigns a score based on the age and sex of a patient as well as the following risk factors for stroke:26

  • Congestive Heart Failure history
  • Hypertension history
  • Stroke/transient ischemic attack (TIA)/thromboembolism history
  • Vascular disease history
  • Diabetes mellitus history

Recent ESC guidelines highly recommend (class I - level A) the CHA2DS2-VASc score for stroke risk prediction in AF patients.27 In general, patients without clinical stroke risk factors do not need antithrombotic therapy, while patients with stroke risk factors (i.e. CHA2DS2-VASc score of 1 or more for men, and 2 or more for women) are likely to benefit from oral anticoagulant therapy.27

 

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