New Oral Anticoagulants for Acute and Long-Term Treatment of Haemodynamically Stable Pulmonary Embolism 

Authors

  • Luca Masotti Internal Medicine, Santa Maria Nuova Hospital, Florence, Italy
  • Gianni Lorenzini Internal Medicine, Santa Maria Nuova Hospital, Florence, Italy and Internal Medicine, Cecina Hospital, Cecina, Italy and Department of Internal Medicine, University of Pisa, Italy
  • Giancarlo Landini Internal Medicine, Santa Maria Nuova Hospital, Florence, Italy
  • Niccolò Bettoni Internal Medicine, Santa Maria Nuova Hospital, Florence, Italy
  • Grazia Panigada Internal Medicine, Pescia Hospital, Pescia, Italy
  • Roberto Cappelli Thrombosis Center, University of Siena, Siena, Italy

DOI:

https://doi.org/10.12974/2312-5470.2014.01.01.1

Keywords:

Pulmonary embolism, new oral anticoagulants, apixaban, dabigatran, edoxaban, rivaroxaban, bleedings, efficacy, safety.

Abstract

Historically, standard treatment of haemodynamically stable pulmonary embolism (PE) in the acute phase consists in parenteral anticoagulants overlapped with oral anticoagulants vitamin K antagonists (VKAs) for at least 5-7 days followed by VKAs alone when their therapeutic range is reached and prolonged for at least three-six months (long term phase). However standard treatment has many pharmacological and practical limitations. For overcoming these limitations, new anticoagulant drugs with better pharmacological profile and easier to use, have been manufactured and tested in pre-clinical and clinical trials with the aim to reach at least non inferiority compared to standard treatment.

In the setting of PE, new oral anticoagulants (NOACs), direct inhibitors of thrombin (dabigatran) or activated factor X (apixaban, edoxaban, rivaroxaban) have been tested in the acute and long-term phases of treatment in phase III randomized clinical trials (RCTs). Rivaroxaban (EINSTEIN-PE study) and apixaban (AMPLIFY study) have been tested directly from diagnosis, dabigatran (RE-COVER I and II studies) and edoxaban (HOKUSAI study) starting after 7-10 days of standard treatment. Overall, these trials have demonstrated that NOACs are effective and safe at least as standard treatment, promising a revolutionary approach to PE treatment in acute/sub-acute PE based on single drug approach or rapid switch from parenteral to oral anticoagulation.

In this paper the Authors focus on phase III RCTs on NOACs in the acute and long-term phases of PE treatment, highlighting the first two weeks of treatment. 

References

Goldhaber S, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353: 1386-1389. http://dx.doi.org/10.1016/S0140-6736(98)07534-5

Wood KE. Major pulmonary embolism. Review of a pathophysiologic approach to the golden hour of hemodinamically significant pulmonary embolism. Chest 2002; 121: 877-905. http://dx.doi.org/10.1378/chest.121.3.877

Miniati M, Monti S, Bottai M. Survival and restoration of pulmonary perfusion in a long-term follow-up of patients after acute pulmonary embolism. Medicine 2006; 85: 253-262. http://dx.doi.org/10.1097/01.md.0000236952.87590.c8

Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology. Eur Heart J 2008; 29: 2276-2315. http://dx.doi.org/10.1093/eurheartj/ehn310

Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet 2012; 379: 1835-46. http://dx.doi.org/10.1016/S0140-6736(11)61904-1

Agnelli G, Becattini C. Acute pulmonary embolism. N Engl J Med 2010; 363: 266-74. http://dx.doi.org/10.1056/NEJMra0907731

Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic Therapy for VTE Disease Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2) (Suppl): e419-e454.

Garcia DA, Baglin TP, Weitz JI, Samama MM. American College of Chest Physicians. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl): e24S-43S.

Ageno W, Gallus AS, Wittkowsky A, Crowther M, Hylek EM, Palareti G. American College of Chest Physicians. Oral anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141(2 Suppl): e44S-88S.

Ogilvie IM, Newton N, Welner SA, Cowell W, Lip GY. Underuse of oral anticoagulants in atrial fibrillation: a systematic review. Am J Med 2010; 123: 638-645. http://dx.doi.org/10.1016/j.amjmed.2009.11.025

Baker WL, Cios DA, Sander SD, Coleman CI. Meta-analysis to assess the quality of warfarin control in atrial fibrillation patients in the United States. J Manag Care Pharm 2009; 15: 244-52.

Weitz J, Eikelboom JW, Samama MM. New antithrombotic drugs: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines Chest 2012; 141(Suppl 2): e120S-e151S.

Baglin T, Keeling D, Kitchen S. Effects on routine coagulation screens and assessment of anticoagulant intensity in patients taking oral dabigatran or rivaroxaban: guidance from the British Committee for Standards in Haematology. Br J Haematol 2012; 159: 427-9. http://dx.doi.org/10.1111/bjh.12052

Samama MM, Guinet C, Le Flem L. Do new oral anticoagulants require laboratory monitoring? The clinician point of view. Thromb Res 2012; 130(Suppl 1): S88-9. http://dx.doi.org/10.1016/j.thromres.2012.08.286

Tripodi A. The laboratory and the new oral anticoagulants. Clin Chem 2013; 59: 353-62. http://dx.doi.org/10.1373/clinchem.2012.189704

Garcia D, Barrett YC, Ramacciotti E, Weitz JI. Laboratory assessment of the anticoagulant effects of the next generation of oral anticoagulants. J Thromb Haemost 2013; 11: 245-52. http://dx.doi.org/10.1111/jth.12096

The EINSTEIN Investigators. Oral rivaroxaban for the treatment of sympromatic pulmonary embolism. N Eng J Med 2012; 366: 1287-97. http://dx.doi.org/10.1056/NEJMoa1113572

Agnelli G, Buller HR, Cohen A, et al. the AMPLIFY Investigators. Oral Apixaban for the Treatment of Acute Venous Thromboembolism. N Engl J Med 2013; 369(9): 799- 808. http://dx.doi.org/10.1056/NEJMoa1302507

Schulman S, Kearon C, Kakkar AK, et al. RE-COVER Study Group. Dabigatran versus warfarin in the treatment of acute venous thromboembolism. N Engl J Med 2009; 361: 2342- 52. http://dx.doi.org/10.1056/NEJMoa0906598

Schulman S. Treatment of venous thromboembolism with dabigatran. Curr Opin Pulm Med 2012; 18: 410-5. http://dx.doi.org/10.1097/MCP.0b013e32835466eb

The Hokusai-VTE Investigators. Edoxaban versus Warfarin for the Treatment of Symptomatic Venous Thromboembolism. N Engl J Med 2013. [Epub ahead ofprint].

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Published

2014-02-05

How to Cite

Masotti, L., Lorenzini, G., Landini, G., Bettoni, N., Panigada, G., & Cappelli, R. (2014). New Oral Anticoagulants for Acute and Long-Term Treatment of Haemodynamically Stable Pulmonary Embolism . Global Journal of Respiratory Care, 1(1), 1–8. https://doi.org/10.12974/2312-5470.2014.01.01.1

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