Venous thromboembolism prophylaxis strategies for people undergoing elective total knee replacement: a systematic review and network meta-analysis.

BACKGROUND: Hospital-associated venous thromboembolism is a major patient safety concern. Provision of prophylaxis to patients admitted for elective total knee replacement surgery has been proposed as an effective strategy to reduce the incidence of venous thromboembolism. We aimed to assess the relative efficacy and safety of all available prophylaxis strategies in this setting. METHODS: We did a systematic review and Bayesian network meta-analyses of randomised controlled trials to assess the relative efficacy and safety of venous thromboembolism prophylaxis strategies and to populate an economic model that assessed the cost-effectiveness of these strategies and informed the updated National Institute for Health and Care Excellence (NICE) guideline recommendations for patients undergoing elective total knee replacement surgery. The Cochrane Library (CENTRAL), Embase, and Medline were last searched on June 19, 2017, with key terms relating to the population (venous thromboembolism and total knee replacement) and the interventions compared, including available pharmacological and mechanical interventions. Outcomes of interest were deep vein thrombosis (symptomatic and asymptomatic), pulmonary embolism, and major bleeding. Risk of bias was assessed, and relevant data extracted from the included randomised controlled trials for the network meta-analyses. Relative risks (RR; with 95% credible intervals [95% CrI]) compared to no prophylaxis, median ranks (with 95% CrI), and the probability of being the best intervention were calculated. The study was done in accordance with PRISMA guidelines. FINDINGS: 25 randomised controlled trials were included in the network meta-analyses. 23 trials (19 interventions; n=15 028) were included in the deep vein thrombosis network, 12 in the pulmonary embolism network (13 interventions; n=15 555), and 19 in the major bleeding network (11 interventions; n=19 797). Risk of bias ranged from very low to high. Rivaroxaban ranked first for prevention of deep vein thrombosis (RR 0·12 [95% CrI 0·06-0·22]). Low molecular weight heparin (LMWH; standard prophylactic dose, 28-35 days) ranked first in the pulmonary embolism network (RR 0·02 [95% CrI 0·00-3·86]) and LMWH (low prophylactic dose, 10-14 days) ranked first in the major bleeding network (odds ratio 0·08 [95% CrI 0·00-1·76]), but the results for pulmonary embolism and major bleeding are highly uncertain. INTERPRETATION: Single prophylaxis strategies are more effective in prevention of deep vein thrombosis in the elective total knee replacement population than combination strategies, with rivaroxaban being the most effective. The results of the pulmonary embolism and major bleeding meta-analyses are uncertain and no clear conclusion can be made other than what is biologically plausible (eg, that no prophylaxis and mechanical prophylaxis strategies should have the lowest risk of major bleeding). FUNDING: National Institute for Health and Care Excellence.

Venous Thromboembolism Prophylaxis Strategies for People Undergoing Elective Total Hip Replacement: A Systematic Review and Network Meta-Analysis.

OBJECTIVES: To assess the efficacy and safety of venous thromboembolism prophylaxis in people undergoing elective total hip replacement. METHODS: Systematic review and Bayesian network meta-analyses of randomized controlled trials were conducted for 3 outcomes: deep vein thrombosis (DVT), pulmonary embolism (PE), and major bleeding (MB). MEDLINE, EMBASE, and Cochrane Library (CENTRAL) databases were searched. Study quality was assessed using the Cochrane risk-of-bias checklist. Fixed- and random-effects models were fitted and compared. The median relative risk (RR) and odds ratio (OR) compared with no prophylaxis, with their 95% credible intervals (CrIs), rank, and probability of being the best, were calculated. RESULTS: Forty-two (n = 24 374, 26 interventions), 30 (n = 28 842, 23 interventions), and 24 (n = 31 792, 15 interventions) randomized controlled trials were included in the DVT, PE, and MB networks, respectively. Rivaroxaban had the highest probability of being the most effective intervention for DVT (RR 0.06 [95% CrI 0.01-0.29]). Strategy of low-molecular-weight heparin followed by aspirin had the highest probability of reducing the risk of PE and MB (RR 0.0011 [95% CrI 0.00-0.096] and OR 0.37 [95% CrI 0.00-26.96], respectively). The ranking of efficacy estimates across the 3 networks, particularly PE and MB, had very wide CrIs, indicating high degree of uncertainty. CONCLUSIONS: A strategy of low-molecular-weight heparin given for 10 days followed by aspirin for 28 days had the best benefit-risk balance, with the highest probability of being the best on the basis of the results of the PE and MB network meta-analyses. Nevertheless, there is considerable uncertainty around the median ranks of the interventions.

Cost-Utility Analysis of Venous Thromboembolism Prophylaxis Strategies for People Undergoing Elective Total Hip and Total Knee Replacement Surgeries in the English National Health Service.

Background: Major orthopedic surgery, such as elective total hip replacement (eTHR) and elective total knee replacement (eTKR), are associated with a higher risk of venous thromboembolism (VTE) than other surgical procedures. Little is known, however, about the cost-effectiveness of VTE prophylaxis strategies in people undergoing these procedures. Aim: The aim of this work was to assess the cost-effectiveness of these strategies from the English National Health Service perspective to inform NICE guideline (NG89) recommendations. Materials and Methods: Cost-utility analysis, using decision modeling, was undertaken to compare 15 VTE prophylaxis strategies for eTHR and 12 for eTKR, in addition to "no prophylaxis" strategy. The analysis complied with the NICE Reference Case. Structure and assumptions were agreed with the guideline committee. Incremental net monetary benefit (INMB) was calculated, vs. the model comparator (LMWH+ antiembolism stockings), at a threshold of £20,000/quality-adjusted life-year (QALY) gained. The model was run probabilistically. Deterministic sensitivity analyses (SAs) were undertaken to assess the robustness of the results. Results: The most cost-effective strategies were LMWH for 10 days followed by aspirin for 28 days (INMB = £530 [95% CI: -£784 to £1,103], probability of being most cost-effective = 72%) for eTHR, and foot pump (INMB = £353 [95% CI: -£101 to £665]; probability of being most cost-effective = 18%) for eTKR. There was considerable uncertainty regarding the cost-effectiveness ranking in the eTKR analysis. The results were robust to change in all SAs. Conclusions: For eTHR, LMWH (standard dose) for 10 days followed by aspirin for 28 days is the most cost-effective VTE prophylaxis strategy. For eTKR, the results are highly uncertain but foot pump appeared to be the most cost-effective strategy, followed closely by aspirin (low dose). Future research should focus on assessing cost-effectiveness of VTE prophylaxis in the eTKR population.