Should new oral anticoagulants replace low-molecular-weight heparin for thromboprophylaxis in orthopaedic surgery?
Current anticoagulant provision is dominated by parenteral low-molecular-weight heparin and oral vitamin K antagonists (VKAs), which indirectly inhibit several steps of the coagulation pathway. Two unmet needs for anticoagulation are safety and ease of use. Safety relates primarily to the incidence of major bleeding, which remains the key concern of orthopaedic surgeons and anaesthetists, over and above any efficacy advantage, and convenience of use, which centres on oral administration replacing the need for injections or monitoring platelets or coagulation with VKA. Recent research efforts towards identifying small-molecule inhibitors of coagulation enzymes as novel therapies for thrombotic disorders have been particularly successful in developing orally available molecules to directly inhibit the key proteases, factors IIa and Xa. Of the new oral anticoagulants in development, dabigatran etexilate (BIBR 1048) and rivaroxaban (BAY 59-7939), which inhibit factors IIa and Xa, respectively, are the most advanced and were approved in Europe in 2008. Based on the available data, we can conclude that dabigatran etexilate is non-inferior to enoxaparin in terms of efficacy and safety, and two different doses (220 and 150 mg/day) have now been approved. The 150 mg/day dose is intended for elderly patients and those with moderate renal impairment, which allows clinicians to decrease the risk of bleeding in the increasing number of fragile patients undergoing major orthopaedic surgery. In conclusion, rivaroxaban is superior in efficacy to enoxaparin, even with the US enoxaparin dosing regimen (30 mg b.i.d.), without significant differences in safety.
Anesthesiology and Intensive Care Department, Cochin Hospital, AP-HP, University Paris 5 Descartes, 27, 75014 Paris, France. nadia.rosencher@cch.aphp.fr
Nadia
N
Rosencher
Lorenn
L
Bellamy
Leila
L
Arnaout
D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects; D000069604:Dabigatran; D004334:Drug Administration Schedule; D065427:Factor Xa Inhibitors; D006470:Hemorrhage / Q000139:chemically induced; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D009025:Morpholines / Q000008:administration & dosage* / Q000009:adverse effects; D019637:Orthopedic Procedures / Q000009:adverse effects*; D011516:Prothrombin / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D000069552:Rivaroxaban; D013876:Thiophenes / Q000008:administration & dosage* / Q000009:adverse effects; D013927:Thrombosis / Q000209:etiology / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors
D000925:Anticoagulants; D001562:Benzimidazoles; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D009025:Morpholines; D011725:Pyridines; D013876:Thiophenes; D014812:Vitamin K; D011516:Prothrombin; C025337:Factor IIa; D000069552:Rivaroxaban; D000069604:Dabigatran