Benefit-to-harm ratio of thromboprophylaxis for patients undergoing major
orthopaedic surgery. A systematic review.
Author(s): Hull RD(1), Liang J, Bergqvist D, Yusen RD.
Affiliation(s): Author information:
(1)Russell D. Hull, Thrombosis Research Unit, University of Calgary, Foothills
Hospital, Room 906 South Tower, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada,
Tel.: +1 403 944 8047, Fax: +1 403 270 7891, E-mail: rdhull@ucalgary.ca.
Publication date & source: 2014, Thromb Haemost. , 111(2):199-212
Surgeons consider the benefit-to-harm ratio when making decisions regarding the
use of anticoagulant venous thromboembolism (VTE) prophylaxis. We evaluated the
benefit-to-harm ratio of the use of newer anticoagulants as thromboprophylaxis in
patients undergoing major orthopaedic surgery using the likelihood of being
helped or harmed (LHH), and assessed the effects of variation in the definition
of major bleeding on the results. A systematic literature search was performed to
identify phase II and phase III studies that compared regulatory
authority-approved newer anticoagulants to the low-molecular-weight heparin
enoxaparin in patients undergoing major orthopaedic surgery. Analysis of outcomes
data estimated the clinical benefit (number-needed-to-treat [NNT] to prevent one
symptomatic VTE) and clinical harm (number-needed-to-harm [NNH] or the NNT to
cause one major bleeding event) of therapies. We estimated each trial's
benefit-to-harm ratio from NNT and NNH values, and expressed this as LHH =
(1/NNT)/(1/NNH) = NNH/NNT. Based on reporting of efficacy and safety outcomes,
most studies favoured enoxaparin over fondaparinux, and rivaroxaban over
enoxaparin. However, when using the LHH metric, most trials favoured enoxaparin
over both fondaparinux and rivaroxaban when they included surgical-site bleeding
that did not require reoperation in the definition of major bleeding. The
exclusion of bleeding at surgical site which did not require reoperation shifted
the benefit-to-harm ratio in favour of the newer agents. Variations in the
definitions of major bleeding may change the benefit-to-harm ratio and
subsequently affect its interpretation. Clinical trials should attempt to improve
the consistency of major bleeding reporting.
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