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Venous Thromboembolism Prophylaxis in Major Orthopedic Surgery: Systematic Review Update

Systematic Review

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Purpose of Review

Assess venous thromboembolism (VTE) prevention interventions with total hip replacement (THR), total knee replacement (TKR), and hip fracture (HFx) surgeries.

Key Messages

  • Few head-to-head treatment comparisons have sufficient evidence. Most studies evaluated low molecular weight heparin (LMWH), not low-risk interventions (such as aspirin and mechanical devices); most reported on total deep vein thrombosis (DVT), an outcome that includes asymptomatic DVT and is thus of unclear clinical value.
  • In THR, LMWH has lower VTE and adverse event risks than unfractionated heparin; LMWH and aspirin have similar risks of VTE and major bleeding; direct thrombin inhibitors (DTI) have lower DVT risk than LMWH but higher major bleeding risk; and higher dose LMWH has lower DVT risk but higher major bleeding risk than lower dose.
  • In TKR, vitamin K antagonists have higher DVT risk than LMWH but lower major bleeding risk; and higher dose DTI has lower DVT risk but higher major bleeding risk than lower dose.

Structured Abstract

Background

Major orthopedic surgeries, such as total knee replacement (TKR), total hip replacement (THR), and hip fracture (HFx) surgery, carry a high risk for venous thromboembolism (VTE)—deep vein thrombosis (DVT) and pulmonary embolism (PE).

Methods

Updating a 2012 review, we compare interventions to prevent VTE after TKR, THR, and HFx surgery. We searched four databases and other sources through June 3, 2016, for randomized controlled trials (RCTs) and large nonrandomized comparative studies (NRCSs) reporting postoperative VTE, major bleeding, and other adverse events. We conducted pairwise meta-analyses, Bayesian network meta-analyses, and strength of evidence (SoE) synthesis.

Results

Overall, 127 RCTs and 15 NRCSs met criteria. For THR: low molecular weight heparin (LMWH) has lower risk than unfractionated heparin (UFH) of various VTE outcomes (moderate to high SoE) and major bleeding (moderate SoE). LMWH and aspirin have similar risks of total PE, symptomatic DVT, and major bleeding (low SoE). LMWH has less major bleeding (low SoE) than direct thrombin inhibitors (DTI), but DTI has lower DVT risks (moderate SoE). LMWH has less major bleeding than vitamin K antagonists (VKA) (high SoE). LMWH and factor Xa inhibitor (FXaI) comparisons are inconsistent across VTE outcomes, but LMWH has less major bleeding (high SoE). VKA has lower proximal DVT risk than mechanical devices (high SoE). Longer duration LMWH has lower risk of various VTE outcome risks (low to high SoE). Higher dose LMWH has lower total DVT risk (low SoE) but more major bleeding (moderate SoE). Higher dose FXaI has lower total VTE risk (low SoE). For TKR: LMWH has lower DVT risks than VKA (low to high SoE), but VKA has less major bleeding (low SoE). FXaI has lower risk than LMWH of various VTE outcomes (low to moderate SoE), but LMWH has less major bleeding (low SoE) and more study-defined serious adverse events (low SoE). Higher dose DTI has lower DVT risk (moderate to high SoE) but more major bleeding (low SoE). Higher dose FXaI has lower risk of various VTE outcomes (low to moderate SoE). For HFx surgery: LMWH has lower total DVT risk than FXaI (moderate SoE).

Conclusions

VTE prophylaxis after major orthopedic surgery trades off lowered VTE risk with possible adverse events—in particular, for most interventions, major bleeding. In THR, LMWH has lower VTE and adverse event risks than UFH, LMWH and aspirin have similar risks of VTE and major bleeding, DTI has lower DVT risk than LMWH but higher major bleeding risk, and higher dose LMWH has lower DVT risk but higher major bleeding risk than lower dose. In TKR, VKA has higher DVT risk than LMWH but lower major bleeding risk, and higher dose DTI has lower DVT risk but higher major bleeding risk than lower dose. In HFx surgery and for other intervention comparisons, there is insufficient evidence to assess both benefits and harms, or findings are inconsistent. Importantly, though, most studies evaluate “total DVT” (an outcome of unclear clinical significance since it includes asymptomatic and other low-risk DVTs), but relatively few studies evaluate PE and other clinically important outcomes. This limitation yields a high likelihood of selective outcome reporting bias. There is also relatively sparse evidence on interventions other than LMWH.

Citation

Balk EM, Ellis AG, Di M, Adam GP, Trikalinos TA. Venous Thromboembolism Prophylaxis in Major Orthopedic Surgery: Systematic Review Update. Comparative Effectiveness Review No. 191. (Prepared by the Brown Evidence-based Practice Center under Contract No. 290-2015-00002-I.) AHRQ Publication No. 17-EHC021-EF. Rockville, MD: Agency for Healthcare Research and Quality; June 2017. www.effectivehealthcare.ahrq.gov/reports/final.cfm. DOI: https://doi.org/10.23970/AHRQEPCCER191.