Robert Bona, MD, FACP
How do oral direct factor Xa inhibitors compare with low-molecular-weight heparin (LMWH) for prophylaxis of venous thromboembolism (VTE) in patients having total knee replacement (TKR) or total hip replacement (THR)?
Included studies compared oral direct factor Xa inhibitors with LMWH in patients who had TKR or THR and reported any of mortality, symptomatic deep venous thrombosis (DVT), nonfatal pulmonary embolism (PE), major bleeding, or bleeding leading to reoperation.
MEDLINE, EMBASE/Excerpta Medica, and Cochrane Central Register of Controlled Trials (all to Dec 2011); abstracts of the Congress of the International Society on Thrombosis and Haemostasis (2003 to 2011); and Annual Proceedings of the American Society of Hematology (2004 to 2011) were hand-searched for randomized controlled trials (RCTs) in any language. 22 RCTs (n = 32 159, 45% to 73% women, mean age 58 to 68 y) met the selection criteria. Drugs assessed were rivaroxaban (8 RCTs); edoxaban (4 RCTs); apixaban (4 RCTs); YM150 (2 RCTs); and betrixaban, razaxaban, TAK442, and LY517717 (1 RCT each). 11 RCTs included patients having THR, 10 included patients having TKR, and 1 included patients having either THR or TKR. Prophylaxis duration ranged from 5 to 39 days, and follow-up was < 14 days in 9 RCTs, 30 to 70 days in 12 RCTs, and ≤ 90 days in 1 RCT. Overall study quality was moderate for trials contributing to the major bleeding outcome and high for RCTs contributing to other outcomes, as assessed by the Grading of Recommendations Assessment, Development, and Evaluation approach.
Meta-analysis showed that factor Xa inhibitors reduced symptomatic DVT more than LMWH; groups did not differ for mortality, nonfatal PE, major bleeding, or bleeding leading to reoperation (Table). Subgroup analysis showed that higher doses of factor Xa inhibitors (odds ratio 2.5, 95% CI 1.4 to 4.5), but not lower doses, increased risk for major bleeding (P = 0.02 for interaction).
In patients having total knee or hip replacement, oral direct factor Xa inhibitors reduced symptomatic deep venous thrombosis compared with low-molecular-weight heparin but did not differ for mortality, pulmonary embolism, or bleeding.
Oral direct factor Xa inhibitors vs low-molecular-weight heparin (LMWH) in total knee or hip replacement*
*DVT = deep venous thrombosis; PE = pulmonary embolism; other abbreviations defined in Glossary. RRR, RRI, NNT, NNH, and CI calculated from control event rates and odds ratios in article using a random-effects model.
†Excludes 1 RCT with 0 events in either group.
‡Excludes 6 RCTs with 0 events in either group.
Bona R. Review: Factor Xa inhibitors reduce DVT more than LMWH in total knee or hip replacement. Ann Intern Med. 2012;157:JC2–5. doi: 10.7326/0003-4819-157-4-201208210-02005
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Published: Ann Intern Med. 2012;157(4):JC2-5.
Prevention/Screening, Venous Thromboembolism.
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