The Role of Low Molecular Weight Heparins for Venous Thromboembolism Prevention in Medical Patients—What Is New in 2019?

Abstract

Low molecular weight heparins and fondaparinux have been the cornerstones for prevention of venous thromboembolism (VTE) in acutely ill medical patients for almost two decades. Guidelines recommend the use of these parenteral anticoagulants for 6 to 14 days but advise against extended-duration thromboprophylaxis after hospital discharge because no compelling scientific evidence has been provided for pharmacological prophylaxis beyond hospital stay. Five large randomized clinical trials, one with low molecular weight heparin and four with nonvitamin K antagonist oral anticoagulants, have failed to show significant clinically relevant benefit in this indication. Obviously, the development of VTE is more complex in medical patients than in patients undergoing major surgical procedures. Thus, it can be expected that guideline recommendations for VTE prevention with low molecular weight heparins or fondaparinux in medical patients will remain unchanged in 2019.

Zusammenfassung

Über zwei Jahrzehnte waren niedermolekulare Heparine und Fondaparinux die Eckpfeiler der venösen Thromboembolie-Prophylaxe für Patienten mit akuten internistischen Erkrankungen. In den Leitlinien wird diese Art der Prophylaxe für 6 bis 14 Tage empfohlen, jedoch wird von einer verlängerten Dauer der Prophylaxe über den Krankenhausaufenthalt hinaus wegen fehlender wissenschaftlicher Evidenz abgeraten. In fünf großen randomisierten Studien, davon eine mit niedermolekularem Heparin und vier mit Nicht-Vitamin K antagonistischen oralen Antikoagulanzien, konnte für diese Indikation kein signifikanter, klinisch relevanter Vorteil nachgewiesen werden. Vermutlich ist die Entstehung venöser Thromboembolien bei internistischen Patienten komplexer als bei Patienten mit chirurgischen Eingriffen. Deshalb ist zu erwarten, dass die Leitlinienempfehlungen zur venösen Thromboembolie-Prophylaxe mit niedermolekularen Heparinen oder Fondaparinux für internistische Patienten auch im Jahr 2019 unverändert bleiben.

Keywords

VTE prevention - medical patients - low molecular weight heparins - nonvitamin K antagonist oral anticoagulants

Schlüsselwörter

Thromboembolie Prophylaxe - internistische Patienten - niedermolekulare Heparine (NMH) - Nicht Vitamin K antagonistische orale Antikoagulanzien (NOAK)

• References

• 1 Cohen AT, Tapson VF, Bergmann JF. , et al; ENDORSE Investigators. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet 2008; 371 (9610): 387-394
• 2 Spyropoulos AC, Raskob GE. New paradigms in venous thromboprophylaxis of medically ill patients. Thromb Haemost 2017; 117 (09) 1662-1670
• 3 Samama MM, Cohen AT, Darmon JY. , et al; Prophylaxis in Medical Patients with Enoxaparin Study Group. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med 1999; 341 (11) 793-800
• 4 Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Vaitkus PT, Goldhaber SZ. ; PREVENT Medical Thromboprophylaxis Study Group. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004; 110 (07) 874-879
• 5 Cohen AT, Davidson BL, Gallus AS. , et al; ARTEMIS Investigators. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006; 332 (7537): 325-329
• 6 Goldhaber SZ, Turpie AGG. Prevention of venous thromboembolism among hospitalized medical patients. Circulation 2005; 111 (01) e1-e3
• 7 Kleber FX, Witt C, Vogel G, Koppenhagen K, Schomaker U, Flosbach CW. ; THE-PRINCE Study Group. Randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease. Am Heart J 2003; 145 (04) 614-621
• 8 Mismetti P, Laporte-Simitsidis S, Tardy B. , et al. Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 2000; 83 (01) 14-19
• 9 Riess H, Haas S, Tebbe U. , et al. A randomized, double-blind study of certoparin vs. unfractionated heparin to prevent venous thromboembolic events in acutely ill, non-surgical patients: CERTIFY study. J Thromb Haemost 2010; 8 (06) 1209-1215
• 10 Hull RD, Schellong SM, Tapson VF. , et al; EXCLAIM (Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization) study. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010; 153 (01) 8-18
• 11 Cohen AT, Spiro TE, Büller HR. , et al; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013; 368 (06) 513-523
• 12 Goldhaber SZ, Leizorovicz A, Kakkar AK. , et al; ADOPT Trial Investigators. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 2011; 365 (23) 2167-2177
• 13 Cohen AT, Harrington RA, Goldhaber SZ. , et al; APEX Investigators. Extended thromboprophylaxis with betrixaban in acutely ill medical patients. N Engl J Med 2016; 375 (06) 534-544
• 14 Spyropoulos AC, Ageno W, Albers GW. , et al; MARINER Investigators. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med 2018; 379 (12) 1118-1127
• 15 AWMF online. Available at: https://www.awmf.org/leitlinien/detail/ll/003-001.html . Accessed December 20, 2018
• 16 Kahn SR, Lim W, Dunn AS. , et al. Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 141 (2, Suppl): e195S-e226S