Anticoagulation management principles

Anticoagulants are among the most frequently prescribed medications in the US.

The most common indications are:

• Stroke prevention in patients with atrial fibrillation

• Prevention and treatment of venous thromboembolism (VTE)

• Prevention of valve thrombosis and arterial thromboembolism in patients with prosthetic heart valves

Atrial fibrillation affects 700 to 775 per 100,000 people in the US.[1]Chugh SS, Havmoeller R, Narayanan K, et al. Worldwide epidemiology of atrial fibrillation: a global burden of disease 2010 study. Circulation. 2014 Feb 25;129(8):837-47. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4151302 http://www.ncbi.nlm.nih.gov/pubmed/24345399?tool=bestpractice.com VTE is a relatively common medical problem with a yearly incidence of approximately 1 in every 1000 adults and a lifetime risk of approximately 8%. It is estimated that more than 1.8 million people in the US will have VTE by the year 2050.​[2]Deitelzweig SB, Johnson BH, Lin J, et al. Prevalence of clinical venous thromboembolism in the USA: current trends and future projections. Am J Hematol. 2011 Feb;86(2):217-20. http://onlinelibrary.wiley.com/doi/10.1002/ajh.21917/full http://www.ncbi.nlm.nih.gov/pubmed/21264912?tool=bestpractice.com [3]Centers for Disease Control and Prevention. CDC Yellow Book 2024: health information for international travel. Aug 2023 [internet publication]. https://wwwnc.cdc.gov/travel/page/yellowbook-home [4]Lutsey PL, Zakai NA. Epidemiology and prevention of venous thromboembolism. Nat Rev Cardiol. 2023 Apr;20(4):248-62. http://www.ncbi.nlm.nih.gov/pubmed/36258120?tool=bestpractice.com ​ Therefore, the number of patients receiving anticoagulants is substantial and is expected to grow with time.

Management of anticoagulants is challenging as they may cause adverse drug events (ADEs), specifically bleeding, which leads to substantial morbidity and mortality. Anticoagulants are the most common drug class associated with an inpatient adverse event and have been shown to be the cause of 41% of deaths attributed to an ADE.[5]US Department of Health and Human Services, Office of Inspector General. Adverse events in hospitals: national incidence among Medicare beneficiaries. November 2010 [internet publication]. https://oig.hhs.gov/oei/reports/oei-06-09-00090.pdf Warfarin is the second most commonly implicated drug in emergency department visits for ADEs in the US.[6]Budnitz DS, Lovegrove MC, Shehab N, et al. Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011 Nov 24;365(21):2002-12. http://www.nejm.org/doi/full/10.1056/NEJMsa1103053#t=article http://www.ncbi.nlm.nih.gov/pubmed/22111719?tool=bestpractice.com Careful and informed management of anticoagulants is therefore critical.

Anticoagulants inhibit the formation and propagation of blood clots and are used in the treatment of many conditions. While individual anticoagulants are specifically approved for a number of disorders, the use of anticoagulants is off-label for others. The level of evidence for use of anticoagulants varies, with a generally lower level of evidence for more rare disorders.

Anticoagulants can be given either orally or parenterally. Warfarin had been used for more than 50 years before dabigatran, the first alternative (non-vitamin K antagonist) oral anticoagulant, was introduced. Since then, many other alternative oral anticoagulants have become available (e.g., apixaban, edoxaban, rivaroxaban). As these newer agents result in anticoagulation by different mechanisms of action than warfarin, a new nomenclature was needed.[7]Link KP. The discovery of dicumarol and its sequels. Circulation. 1959 Jan;19(1):97-107. http://www.ncbi.nlm.nih.gov/pubmed/13619027?tool=bestpractice.com  The naming of these new drugs has been controversial and has evolved over time. Published terms have included: new, novel, or non-vitamin K antagonist oral anticoagulants (NOACs); target-specific oral anticoagulants (TSOACs); and direct oral anticoagulants (DOACs). A 2014 survey study administered to 150 leaders of 16 professional societies in North America and Europe identified DOACs as the favored term.[8]Barnes GD, Ageno W, Ansell J, et al. Recommendation on the nomenclature for oral anticoagulants: communication from the SSC of the ISTH. J Thromb Haemost. 2015 Jun;13(6):1154-6. https://www.jthjournal.org/article/S1538-7836(22)12799-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/25880598?tool=bestpractice.com ​ As new therapeutic agents, which target Factors XI and XII, are emerging, a new nomenclature system has been developed based on route of administration and specific mechanism of action.[8]Barnes GD, Ageno W, Ansell J, et al. Recommendation on the nomenclature for oral anticoagulants: communication from the SSC of the ISTH. J Thromb Haemost. 2015 Jun;13(6):1154-6. https://www.jthjournal.org/article/S1538-7836(22)12799-6/fulltext http://www.ncbi.nlm.nih.gov/pubmed/25880598?tool=bestpractice.com [9]Fredenburgh JC, Weitz JI. News at XI: moving beyond factor Xa inhibitors. J Thromb Haemost. 2023 Jul;21(7):1692-702. https://www.jthjournal.org/article/S1538-7836(23)00343-4/fulltext http://www.ncbi.nlm.nih.gov/pubmed/37116752?tool=bestpractice.com