BACKGROUND: The purpose of this study is to perform a meta-analysis to compare outcomes of venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) vs other anticoagulants in patients who received total knee (TKA) or total hip arthroplasty (THA).
METHODS: MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched until June 30, 2017 for eligible randomized controlled studies.
RESULTS: Thirty-two randomized controlled studies were included. LMWH provided better protection against VTE than placebo. In both TKA and THA patients, the rates of VTE were lower with factor Xa inhibitors than LMWH. In THA patients, the rate of deep vein thrombosis (DVT) was lower with factor Xa inhibitors than LMWH. In TKA patients, the rates of VTE and DVT were similar between LMWH and direct thrombin inhibitors. In THA patients, the rate of VTE was lower with direct thrombin inhibitors than with LMWH, while the DVT rates were similar. The pulmonary embolism rates were similar between all 3 classes of drugs in TKA and THR patients, as were the major bleeding rates. Nonmajor and minor bleeding rates were also similar between the 3 drug classes.
CONCLUSION: LMWH is associated with a higher rate of VTE than factor Xa inhibitors in TKA and THA patients. Direct thrombin inhibitors are associated with a lower rate of VTE in THA patients, but their effectiveness with respect to DVT and pulmonary embolism prophylaxis is similar to that of LMWH in TKA and THA patients.
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.
BACKGROUND: Venous thromboembolism (VTE) is an important complication following total hip replacement (THR) and total knee replacement (TKR) surgeries. Aim of this study was to comprehensively compare the clinical outcomes of low-molecular-weight heparin (LMWH) with other anticoagulants in patients who underwent TKR or THR surgery.
METHODS: Medline, Cochrane, EMBASE, and Google Scholar databases were searched for eligible randomized controlled studies (RCTs) published before June 30, 2017. Meta-analyses of odds ratios were performed along with subgroup and sensitivity analyses.
RESULTS: Twenty-one RCTs were included. In comparison with placebo, LMWH treatment was associated with a lower risk of VTE and deep vein thrombosis (DVT) (P values < 0.001) but similar risk of pulmonary embolism (PE) (P = 0.227) in THR subjects. Compared to factor Xa inhibitors, LMWH treatment was associated with higher risk of VTE in TKR subjects (P < 0.001), and higher DVT risk (P < 0.001) but similar risk of PE and major bleeding in both THR and TKR. The risk of either VTE, DVT, PE, or major bleeding was similar between LMWH and direct thrombin inhibitors in both THR and TKR, but major bleeding was lower with LMWH in patients who underwent THR (P = 0.048).
CONCLUSION: In comparison with factor Xa inhibitors, LMWH may have higher risk of VTE and DVT, whereas compared to direct thrombin inhibitors, LMWH may have lower risk of major bleeding after THR or TKR.
Background: Venous thromboembolism (VTE) is a potentially fatal complication of orthopedic surgery, and until recently, few antithrombotic compounds were available for postoperative thromboprophylaxis. The introduction of the non–vitamin K antagonists oral anticoagulants (NOAC), including apixaban, has extended the therapeutic armamentarium in this field. Therefore, estimation of NOAC net clinical benefit in comparison with the established treatment is needed to inform clinical decision making. Objectives: Systematic review to assess the efficacy and safety of apixaban 2.5 mg twice a day versus low-molecular-weight heparins (LMWH) for thromboprophylaxis in patients undergoing knee or hip replacement. Data sources: MEDLINE, Embase, and CENTRAL were searched from inception to September 2016, other systematic reviews, reference lists, and experts were consulted. Study eligibility criteria, participants, and intervention: All major orthopedic surgery randomized controlled trials comparing apixaban 2.5 mg twice daily with LMWH, reporting thrombotic and bleeding events. Data extraction: Two independent reviewers, using a predetermined form. Study appraisal and synthesis methods: The Cochrane tool to assess risk bias was used by two independent authors. RevMan software was used to estimate pooled risk ratio (RR) and 95% confidence intervals (95% CI) using random-effects meta-analysis. Trial sequential analysis (TSA) was performed in statistical significant results to evaluate whether cumulative sample size was powered for the obtained effect. Overall confidence in cumulative evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group methodology. Results: Four studies comparing apixaban 2.5 mg twice daily with LMWH were included, with a total of 11.828 patients (55% undergoing knee and 45% hip replacement). The overall risk of bias across studies was low. In comparison with LMWH (all regimens), apixaban showed a significantly lower risk of VTE events and overall mortality combined (RR: 0.63, 95% CI: 0.42-0.95, I2 = 84%, n = 8346), but not of major VTE events (RR: 0.62, 95% CI: 0.32-1.19, I2 = 63%, n = 9493), or of symptomatic VTE events and VTE-related mortality combined (RR: 1.14, 95% CI: 0.68-1.90, I2 = 0%, n = 11 879). Trial sequential analysis showed that the risk reduction obtained for VTE and mortality was based on underpowered cumulative sample size and effect dimension. Subgroup analysis according to LMWH regimens showed that apixaban reduced the risk of VTE events and overall mortality, and major VTE events, when compared with LMWH once daily, without differences between apixaban and LMWH twice daily. Conclusions: There is low to moderate evidence that in patients undergoing knee or hip replacement, apixaban seems equally effective and safe to LMWH twice a day. When compared with LMWH once a day, apixaban seems a superior thromboprophylaxis option. However, the results are underpowered which precludes definite answers regarding the true net clinical benefit of apixaban versus LMWH in this clinical context.
ESSENTIALS: Despite trial data, guidelines have not endorsed direct oral Xa inhibitors above other options. We provide profiles of venous thromboembolism and hemorrhage risk for 12 options. Direct oral Xa inhibitors had a favorable profile compared with low-molecular-weight heparin. Other options did not have favorable profiles compared with low-molecular-weight heparin.
SUMMARY:
BACKGROUND: There are numerous trials and several meta-analyses comparing venous thromboembolism (VTE) prophylaxis options after total hip and knee replacement (THR and TKR). None have included simultaneous comparison of new with older options. Objective To measure simultaneously the relative risk of VTE and hemorrhage for 12 prophylaxis options. METHODS: We abstracted VTE and hemorrhage information from randomized controlled trials published between January 1990 and June 2016 comparing 12 prophylaxis options. We then constructed networks to compute the relative risk for each option, relative to once-daily dosing with low-molecular-weight heparin (LMWH) Low. RESULTS MAIN: Relative to LMWH Low, direct oral Xa inhibitors had the lowest risk of total deep vein thrombosis (DVT)-asymptomatic and symptomatic- (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.35-0.57), translating to 53-139 fewer DVTs per 1000 patients. Vitamin K antagonists (VKAs) titrated to International Normalized Ratio [INR] 2-3 predicted 56% more DVT events (OR, 1.56; 95% CI, 1.14-2.14). Aspirin performed similarly (OR, 0.80; 95% CI, 0.34-1.86), although small numbers prohibit firm conclusions. Direct oral Xa inhibitors did not lead to significantly more bleeding (OR, 1.21; 95% CI, 0.79-1.90). Secondary: Relative to LMWH Low, direct oral Xa inhibitors prevented 4-fold more symptomatic DVTs (OR, 0.25; 95% CI, 0.13-0.47). CONCLUSIONS: Relative to LMWH Low, direct oral Xa inhibitors had a more favorable profile of VTE and hemorrhage risk, whereas VKAs had a less favorable profile. The profile of other agents was not more or less favorable. Clinicians should consider these profiles when selecting prophylaxis options.
BACKGROUND: Venous thromboembolism causes significant morbidity and mortality in patients after total joint arthroplasty. Although network meta-analyses have demonstrated a benefit of various thromboprophylactic agents, there remains a concern in the surgical community regarding the resulting wound complications. There is currently no systematic review of the surgical site bleeding complications of thromboprophylactic agents. The aim of this study was to systematically review the surgical site bleeding outcomes of venous thromboembolism prophylaxis in this population.
METHODS: A systematic review and meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Randomized controlled trials comparing more than one of low-molecular-weight heparin (LMWH), warfarin, rivaroxaban, apixaban, dabigatran, aspirin, or no pharmacologic treatment in patients after total hip or knee arthroplasty were selected for inclusion. Five meta-analyses were performed to compare LMWH with control, warfarin, apixaban, rivaroxaban, and dabigatran.
RESULTS: Forty-five randomized controlled trials of 56,730 patients were included. LMWH had a significantly increased relative risk of surgical site bleeding in comparison with control (relative risk, 2.32; 95% confidence interval, 1.40-3.85) and warfarin (1.54; 1.23-1.94). The relative risk of LMWH trended higher than apixaban (1.27; 1.00-1.63) and was similar to rivaroxaban (0.95; 0.74-1.23). Only 1 study reported the risk of surgical site bleeding in LMWH vs dabigatran (5.97; 2.08-17.11).
CONCLUSION: LMWH increased the risk of surgical site bleeding compared with control, warfarin. and dabigatran and trended toward an increased risk compared with apixaban. The risk of surgical site bleeding was similar with LMWH and rivaroxaban.
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.
BACKGROUND: A symptomatic pulmonary embolism (PE) after total joint arthroplasty has been described as a "never event." Despite potent anticoagulants and improvements in patient care, PE continues to occur following total hip arthroplasty (THA). This study evaluates symptomatic PE rates over time in THA patients enrolled in multicenter randomized clinical trials (RCTs) assessing the efficacy of venous thromboembolism prophylaxis regimens.
METHODS: The MEDLINE and Cochrane Central Register of Controlled Trials were searched to identify clinical trials assessing prophylactic anticoagulation in patients undergoing THA between January 1995 and December 2015. Inclusion criteria consisted of RCTs evaluating prophylactic anticoagulation in patients undergoing THA. A random effect model was used to combine PE rates across studies.
RESULTS: A total of 21 studies (34,764 patients) were included. Patients were administered low molecular weight heparin (13,590 patients), oral factor Xa inhibitors (6609 patients), oral direct thrombin inhibitors (5965 patients), indirect factors Xa/IIa inhibitors (3444 patients), aspirin (2427 patients), and warfarin (489 patients). Mobile compression was used in 199 patients, and placebo was used in 2041 patients. Across all included studies, the estimated PE rate was 0.21% (95% confidence interval: 0.13%, 0.32%). Between 1997 and 2013, the proportion of PEs did not change in regression analysis.
CONCLUSION: Although the PE rate was low, it was consistent throughout the 17 years spanning these RCTs, which excluded patients with significant morbidity. These results suggest that even healthy THA patients receiving aggressive anticoagulation still have a risk for PE, and the "never event" designation requires reassessment.
We carried out a dose-response model-based meta-analysis to assess venous thromboembolism (VTE) and bleeding with factor Xa (FXa) inhibitors (apixaban, edoxaban, rivaroxaban) and a thrombin inhibitor (dabigatran) compared with European (EU) (40 mg q.d.) and North American (NA) (30 mg Q12H) dose regimens of a low molecular weight heparin (enoxaparin) following orthopedic surgery. Statistically significant differences in both VTE and bleeding outcomes were found between the NA and EU doses of enoxaparin, with odds ratios (95% confidence interval) for the NA vs. EU dose of 0.73 (0.71-0.76) and 1.20 (1.14-1.29) for total VTE and major bleeding, respectively. At approved doses, estimated odds ratios vs. both doses of enoxaparin for the three FXa inhibitors (range: 0.35-0.75 for VTE; 0.76-1.09 for bleeding) compared with those for dabigatran (range: 0.66-1.21 for VTE; 1.10-1.38 for bleeding) suggested generally greater efficacy and less bleeding for the FXa inhibitors.
Journal»International Journal of Clinical and Experimental Medicine
Year»2016
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OBJECTIVE: The aim of this meta-analysis is to estimate efficacy and safety of different daily doses of oral direct factor Xa inhibitor for thromboprophylaxis after total hip or knee replacement. METHODS: This paper searched the databases such as Pubmed, Medline, Web of Science and Embase databases. 15 RCT studies were included and dichotomousdata were presented as the risk ratio (RR) with a 95% confidence interval (CI). RESULTS: 15 relevant studies with 28, 548 individuals and 3 different types of oral direct factor Xa inhibitor (apixaban, rivaroxaban and dabigatran) were employed for this meta-analysis. The efficacy of 5 mg, 10 mg and 20 mg daily doses of apixaban was superior to 40 mg daily of enoxaparin, but 10 mg and 20 mg daily doses of apixaban increased the risk of major bleeding and non-major but clinically relevant bleeding. Except the lowest daily dose of 5 mg, 10 mg, 20 mg, 30 mg, 40 mg and 60 mg daily doses of rivaroxaban had superior efficacy than 40 mg daily of enoxaparin, but higher doses of 30 mg, 40 mg and 60 mg showed lower safety than enoxaparin and 10 mg and 20 mg of rivaroxaban. 60 mg daily was better in efficacy than enoxaparin and other doses of darexaban. Meantime, the risk of bleeding was not significantly increasing. CONCLUSION: Consider the safety and efficacy, 5 mg daily of apixaban, 20 mg daily of rivaroxaban, 60 mg daily of darexaban were optimal potential oral direct factor Xa inhibitor for thromboprophylaxis after total hip or knee replacement.
The purpose of this study is to perform a meta-analysis to compare outcomes of venous thromboembolism (VTE) prophylaxis with low-molecular-weight heparin (LMWH) vs other anticoagulants in patients who received total knee (TKA) or total hip arthroplasty (THA).
METHODS:
MEDLINE, Cochrane, EMBASE, and Google Scholar databases were searched until June 30, 2017 for eligible randomized controlled studies.
RESULTS:
Thirty-two randomized controlled studies were included. LMWH provided better protection against VTE than placebo. In both TKA and THA patients, the rates of VTE were lower with factor Xa inhibitors than LMWH. In THA patients, the rate of deep vein thrombosis (DVT) was lower with factor Xa inhibitors than LMWH. In TKA patients, the rates of VTE and DVT were similar between LMWH and direct thrombin inhibitors. In THA patients, the rate of VTE was lower with direct thrombin inhibitors than with LMWH, while the DVT rates were similar. The pulmonary embolism rates were similar between all 3 classes of drugs in TKA and THR patients, as were the major bleeding rates. Nonmajor and minor bleeding rates were also similar between the 3 drug classes.
CONCLUSION:
LMWH is associated with a higher rate of VTE than factor Xa inhibitors in TKA and THA patients. Direct thrombin inhibitors are associated with a lower rate of VTE in THA patients, but their effectiveness with respect to DVT and pulmonary embolism prophylaxis is similar to that of LMWH in TKA and THA patients.
Systematic Review Question»Systematic review of interventions
