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Indications for vitamin K antagonist therapy

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

Indications for vitamin K antagonist therapy and INR testing

 

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

 

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.

Causes of heart valve defects:3

  • Congenital heart valve defect in the infant.
  • Rheumatic fever - rarely seen now in western industrial nations
  • Changes to the valvular apparatus due to infection, immunological, ischemic, traumatic or degenerative factors

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

  • With mechanical aortic valve, VKA therapy with a target INR of 2.5 (range 2.0 to 3.0) is recommended (Grade 1B recommendation)
  • With mechanical mitral valve, VKA therapy with a target INR of 3.0 (range 2.5 to 3.5) is recommended (Grade 2C recommendation)
  • With mechanical valves in both the aortic and mitral position, a target INR of 3.0 (range 2.5 to 3.5) is recommended (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, LV dysfunction, hypercoagulable conditions, older-generation thrombogenic valves, mechanical tricuspid valves, or more than 1 mechanical valve.8

 
  • Atrial fibrillation

 

Atrial fibrillation 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 atrial fibrillation (AF).12 The risk of stroke in AF patients increases with age, from a 1.5% annual risk in patients aged 50-59 years to 23.5% in 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 atrial fibrillation and atrial fibrillation is regarded as one of the major risk factors for thromboembolic-caused stroke.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. Below 2.0, patients have an increased risk for ischemic stroke, and above 3.0, the risk for intracranial bleeding begins to rise.19-23 

This was confirmed recently by the BAFTA study showing that stroke risk is lowered by 64% with warfarin treatment compared to no treatment, and stroke is reduced by 22 % with antiplatelet agents.24 Warfarin was therefore found to be 39% more efficacious than antiplatelet therapy and was appropriate for use in an elderly population.24

Where oral anticoagulation is indicated, a risk stratification (e.g. using the CHA2DS2-VASc score) should 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/TIA/Thromboembolism histroy
  • 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

 

 

 

  • Deep vein thrombosis and pulmonary embolism
  • Myocardial infarction
  • Acute ischemic stroke

In the spotlight

  1. Vongpatanasin W, Hillis LD, Lange RA. Prosthetic Heart Valves. N Engl J Med 1996; 335:407-416.
  2. Gohlke-Barwolf C. [Current recommendations for prevention of thromboembolism in patients with heart valve prostheses] (german article). Z Kardiol 2001; 90 Suppl 6:112-117.
  3. Braunwald E. Valvular heart disease. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison's principles of internal medicine. New York: McGraw-Hill, 2001; 1343-1355.
  4. Carabello BA, Crawford FA. Valvular Heart Disease. N Engl J Med 1997; 337:32-41.
  5. Ennker Jr, Lauruschkat A. Mechanische vs. biologische Herzklappen. Z Kardiol 2001; 90.
  6. Helmut Baumgartner, Volkmar Falk, Jeroen J Bax, Michele De Bonis, Christian Hamm, Per Johan Holm, Bernard Iung, Patrizio Lancellotti, Emmanuel Lansac, Daniel Rodriguez Muñoz, Raphael Rosenhek, Johan Sjögren, Pilar Tornos Mas, Alec Vahanian, Thomas Walther, Olaf Wendler, Stephan Windecker, Jose Luis Zamorano, ESC Scientific Document Group, 2017 ESC/EACTS Guidelines for the management of valvular heart disease, European Heart Journal, Volume 38, Issue 36, 21 September 2017, Pages 2739–2791
  7. Whitlock RP, Sun JC, Fremes SE, Rubens FD, Teoh KH, American College of Chest Physicians. Antithrombotic and thrombolytic therapy for valvular disease: Antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-based clinical practice guidelines. Chest 2012;141(2 Suppl):e576S-600S.
  8. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: Executive summary: A report of the american college of Cardiology/American heart association task force on practice guidelines. Circulation 2014;129:2440-9
  9. Koertke H, Korfer R. International normalized ratio self-management after mechanical heart valve replacement: is an early start advantageous? Ann Thorac Surg 2001; 72:44-48.
  10. Koertke H, Zittermann A, Minami K, et al. Low-dose international normalized ratio self-management: a promising tool to achieve low complication rates after mechanical heart valve replacement. Ann Thorac Surg 2005; 79:1909-1914; discussion 1914.
  11. Clinical Excellence Commission, 2017, Non-vitamin K Antagonist Oral Anticoagulant (NOAC) Guidelines are available at: http://www.cec.health.nsw.gov.au/

 
  1. Vongpatanasin W, Hillis LD, Lange RA. Prosthetic Heart Valves. N Engl J Med 1996; 335:407-416.
  2. Gohlke-Barwolf C. [Current recommendations for prevention of thromboembolism in patients with heart valve prostheses] (german article). Z Kardiol 2001; 90 Suppl 6:112-117.
  3. Braunwald E. Valvular heart disease. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. Harrison's principles of internal medicine. New York: McGraw-Hill, 2001; 1343-1355.
  4. Carabello BA, Crawford FA. Valvular Heart Disease. N Engl J Med 1997; 337:32-41.
  5. Ennker Jr, Lauruschkat A. Mechanische vs. biologische Herzklappen. Z Kardiol 2001; 90.
  6. Koertke H, Korfer R. International normalized ratio self-management after mechanical heart valve replacement: is an early start advantageous? Ann Thorac Surg 2001; 72:44-48.
  7. Koertke H, Zittermann A, Minami K, et al. Low-dose international normalized ratio self-management: a promising tool to achieve low complication rates after mechanical heart valve replacement. Ann Thorac Surg 2005; 79:1909-1914; discussion 1914.
  8. From: ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease Journal of the American College of Cardiology Vol. 48, No. 3, 2006 Bonow RO, Carabello BA, Chatterjee K, de Leon AC Jr., Faxon DP, Freed MD, Gaasch WH, Lytle BW, Nishimura RA, O’Gara PT, O’Rourke RA, Otto CM, Shah PM, Shanewise JS. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Valvular Heart Disease), American College of Cardiology Web Site: http://www.acc.org/clinical/guidelines/valvular/ index.pdf