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Evaluation of Exercise Interventions and Outcomes After Hip Arthroplasty: A Systematic Review and Meta-analysis.
Saueressig, T, Owen, PJ, Zebisch, J, Herbst, M, Belavy, DL
JAMA network open. 2021;(2):e210254
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IMPORTANCE Preoperative and postoperative exercise interventions are commonly used in patients with total hip arthroplasty despite a lack of established efficacy. OBJECTIVE To explore clinical outcomes associated with exercise training before and after hip arthroplasty. DATA SOURCES PubMed, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, and Google Scholar were searched from their inception to March 2020. Reference lists of included trials and related reviews were also searched. STUDY SELECTION Randomized clinical trials of land-based exercise interventions before or after total hip arthroplasty were included. DATA EXTRACTION AND SYNTHESIS This systematic review and meta-analysis is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data extraction was independently performed in duplicate. Random-effects meta-analyses with restricted maximum likelihood were performed for pooling the data. MAIN OUTCOMES AND MEASURES The primary prespecified outcome was self-reported physical function. Secondary prespecified outcomes were self-reported pain intensity, quality of life, gait speed, lower body muscle strength, lower body flexibility, anxiety, hospital length of stay, and adverse events. RESULTS A total of 32 randomized clinical trials with 1753 patients were included in the qualitative synthesis, and 26 studies with 1004 patients were included in the meta-analysis. Compared with usual care or no or minimal intervention, postoperative exercise training was not associated with improved self-reported physical function, with a moderate level of certainty, at 4 weeks (standardized mean difference [SMD], 0.01; 95% CI, -0.18 to 0.20), 12 weeks (SMD, -0.08; 95% CI, -0.23 to 0.07) and 26 weeks (SMD, -0.04; 95% CI, -0.31 to 0.24) postoperatively, and low level of certainty at 1 year after surgical treatment (SMD, 0.01; 95% CI, -0.09 to 0.12). For preoperative exercise interventions, there was no association of exercised training with self-reported physical function compared with the control at the 12-week (SMD, -0.14; 95% CI, -0.61 to 0.32) or 1-year follow-ups (SMD, 0.01; 95% CI, -0.37 to 0.40) with very low certainty, and no association with length of stay (mean difference, -0.21; 95% CI, -0.74 to 0.31) at moderate certainty. Results for postoperative hip muscle strength were rated at very low certainty, with no statistical significance. Meta-analysis could not be performed for other outcomes. CONCLUSIONS AND RELEVANCE This systematic review and meta-analysis found low- to moderate-quality evidence that postoperative exercise interventions were not associated with improved self-reported physical function compared with usual care or no or minimal intervention. Furthermore, there was very low-quality evidence that preoperative exercise programs were not associated with higher self-reported physical function and hospital length of stay compared with usual care or no or minimal intervention.
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Vitamin E-Enhanced Liners in Primary Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.
Cheng, QY, Zhang, BF, Wen, PF, Wang, J, Hao, LJ, Wang, T, Cheng, HG, Wang, YK, Guo, JB, Zhang, YM
BioMed research international. 2021;:3236679
Abstract
OBJECTIVE Adding vitamin E to highly cross-linked polyethylene liners is frequently performed in clinical practice, aiming at reducing liner wear, increasing liner survival, and delaying revision surgery. This study is aimed at evaluating the revision rate, total femoral head penetration, and postoperative clinical function of highly cross-linked polyethylene liners with and without vitamin E in total hip arthroplasty. METHODS We conducted a systematic literature search to identify the use of highly cross-linked vitamin E liners compared to other liners in patients who received total hip arthroplasty (THA) before April 2021. The study quality assessment and data collection were conducted by two independent reviewers. Studies were artificially grouped, and vitamin E-enhanced liners (VE-PE) were compared with vitamin E-free liners (non-VE-PE). Analyses were executed using Review Manager version 5.4.1. RESULTS From the preliminary screening of 568 studies, fourteen studies met the research criteria. Compared to non-VE-PE, using VE-PE reduced the all-cause revision rate (odds ratio = 0.54; 95% confidence interval (CI) 0.40, 0.73; P < 0.0001). The total femoral head penetration of the VE-PE was lower than that of the non-VE-PE (mean difference = -0.10; 95% CI -0.17, -0.03; P = 0.007). However, there was no difference in clinical function, including the Harris Hip Score and EuroQol Five-Dimension Questionnaire scores. CONCLUSION Compared to the liners without vitamin E, the addition of vitamin E to liners could reduce the all-cause revision rate by approximately 46% in the short-term follow-up. In addition, even though addition of vitamin E could also slow down femoral head penetration, there is no contribution to clinical function.
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Does vitamin E highly-crosslinked polyethylene convey an advantage in primary total hip replacement? A systematic review and meta-analysis.
Wyatt, MC, Roberton, A, Foxall-Smi, M, Beswick, AD, Kunutsor, SK, Whitehouse, MR
Hip international : the journal of clinical and experimental research on hip pathology and therapy. 2020;(5):598-608
Abstract
BACKGROUND Vitamin E highly cross-linked polyethylene (HXLPE) was developed to reduce wear in total hip replacement (THR). This formal systematic review and meta-analysis aimed to provide independent synthesis of wear characteristics of Vitamin E treated HXLPE compared to HXPLE/UHMWPE. Secondary outcome measures were differences in revision rates and functional scores. METHODS We performed a formal systematic review as per PRISMA guidelines; literature searches were conducted on 14 November 2017 (MEDLINE, Embase on Ovid, and the Cochrane Library). We included randomised controlled trials, analyses of joint registries, and case-controlled studies of primary THR comparing cups with a vitamin E HXLPE bearing with bearing surfaces made from other types of polyethylene. Initial screening was performed by 2 independent assessors; disagreement resolved in discussion with a third reviewer. Studies were evaluated using the Cochrane risk of bias tool. Data extraction permitted meta-analysis. RESULTS 372 studies were identified on initial screening, 5 studies met the eligibility criteria. There was no significant heterogeneity between studies. There was variable risk of bias. At a mean of 35 (range 20-60) months, Vitamin E HXLPE had significant advantages over highly cross-linked polyethylene with regards total femoral head penetration (p = 0.004). Given the RSA measurement errors this may not be clinically significant.There were neither significant differences in revision rates nor Harris Hip Scores (p = 0.06). CONCLUSION At a minimum of 3 years follow-up there was reduced total femoral head penetration for vitamin E HXLPE over HXLPE. This bearing surface does not, as yet, have clinically significant advantages in terms of revision rates or patient function over HXLPE.
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Host-related factors for venous thromboembolism following total joint replacement: A meta-analysis of 89 observational studies involving over 14 million hip and knee replacements.
Barrett, MC, Whitehouse, MR, Blom, AW, Kunutsor, SK
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association. 2020;(2):267-275
Abstract
BACKGROUND Venous thromboembolism, a potential complication of total joint replacement, is associated with preventable mortality and morbidity and is likely to be influenced by host-related factors such as sociodemographic characteristics, body mass index, medical and surgical histories, as well as circulating biomarkers. We conducted a systematic review and meta-analysis to assess the associations between host-related factors and venous thromboembolism risk following total hip and knee replacements. METHODS We searched MEDLINE, Embase, Web of Science, and Cochrane Library to March 2018 for longitudinal studies reporting these associations. Summary measures of association were relative risks (95% confidence intervals). RESULTS We identified 89 studies with data on 14,763,963 joint replacements and 150,086 venous thromboembolism events. Comparing males to females, age ≥70 to <70 years, and blacks to whites, relative risks for venous thromboembolism were 0.83 (0.75-0.91), 1.24 (1.03-1.50), and 1.26 (1.20-1.31) respectively. Comparing body mass indices ≥25 vs. <25; ≥30 vs. <30; and ≥50 vs. <50 kg/m2, relative risks were 1.40 (1.24-1.57); 1.65 (1.23-2.22); and 1.72 (1.10-2.67) respectively. Histories of venous thromboembolism; cardiovascular disease; congestive heart failure; cardiac arrhythmia; chronic pulmonary disease; renal disease; neurological disease; fluid & electrolyte imbalance; bariatric surgery; and comorbidity indices were associated with increased venous thromboembolism risk. Comparing a total knee with a hip replacement, the relative risk for venous thromboembolism was 1.69 (1.32-2.15). CONCLUSIONS Enhanced venous thromboembolism prophylaxis should be considered in those with nonmodifiable risk factors such as older black female knee replacement patients. Modifiable risk factors such as high body mass index and fluid & electrolyte imbalance should be addressed prior to elective surgery. SYSTEMATIC REVIEW REGISTRATION PROSPERO 2018: CRD42018089625.
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Association of malnutrition with periprosthetic joint and surgical site infections after total joint arthroplasty: a systematic review and meta-analysis.
Tsantes, AG, Papadopoulos, DV, Lytras, T, Tsantes, AE, Mavrogenis, AF, Korompilias, AV, Gelalis, ID, Tsantes, CG, Bonovas, S
The Journal of hospital infection. 2019;(1):69-77
Abstract
BACKGROUND A growing body of evidence associates malnutrition with several adverse outcomes. AIM: To investigate the link between malnutrition with surgical site and periprosthetic joint infections (SSIs and PJIs) following total knee and hip arthroplasty (TKA and THA) through a comprehensive meta-analysis of observational studies. METHODS A systematic search was conducted on PubMed and Scopus databases through December 2018, and recent proceedings of major orthopaedic meetings. Data from eligible studies were extracted and synthesized; pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated. FINDINGS Seven publications were included, reporting eight independent cohort studies with >250,000 subjects. SSIs and PJIs were more likely to develop in malnourished patients (OR: 2.49; 95% CI: 2.13-2.90; and 3.62; 2.33-5.64, respectively). The association of SSI with malnutrition was evident both after TKA (2.42; 1.94-3.02) and after THA (2.66; 1.64-4.30). Similarly, PJI was associated with malnutrition after TKA (2.55; 1.10-5.91) and after THA (3.10; 1.84-5.25). Finally, PJI correlated with malnutrition both after primary arthroplasty (3.58; 1.82-7.03) and revision arthroplasty (3.96; 2.47-6.33). The subgroup analysis by study setting confirmed the relationship between PJI and malnutrition in hospital (6.02; 3.07-11.81) and population-based (2.80; 1.76-4.44) studies. CONCLUSION Malnutrition is associated with PJIs and SSIs after total joint arthroplasty. Further high-quality research is warranted to confirm or refute these findings.
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Is Oxidized Zirconium Femoral Head Superior to Other Bearing Types in Total Hip Arthroplasty? A Systematic Review and Meta-Analysis.
Malahias, MA, Atrey, A, Gu, A, Chytas, D, Nikolaou, VS, Waddell, JP
The Journal of arthroplasty. 2019;(8):1844-1852
Abstract
BACKGROUND Oxidized zirconium (OxZi) is a relatively new type of material that combines the strength of a metal with the surface/wears properties of a ceramic. Our aim was to investigate whether OxZi femoral heads lead to lower polyethylene wear, higher survival rate, and better clinical outcomes than the other bearing types in patients treated with total hip arthroplasty (THA). METHODS Two reviewers independently conducted a systematic search according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses using the MEDLINE/PubMed database and the Cochrane Database of Systematic Reviews. These databases were queried with the terms: a. "oxidized" AND "zirconium" AND "total" AND "hip" AND "arthroplasty"; b. "oxinium" AND "total" AND "hip" AND "arthroplasty". The primary outcome measures were the survival rate of the bearing surfaces as well as the polyethylene wear. RESULTS The vast majority (85.7%) of the studies, which reported the mean polyethylene wear rate, showed that there was not any significant difference between OxZi and cobalt-chrome (CoCr) femoral heads (rate ratio: 0.836; 95% confidence interval: 0.362-1.928; P = .674). All studies comparing the survival rate of OxZi and CoCr femoral heads illustrated almost excellent survivorship with both implants. CONCLUSION OxZi femoral heads did not lead to lower polyethylene wear rate or higher survival rate, when compared with CoCr femoral heads in patients treated with THA. On the basis of these results and taking into account the higher cost of these implants, we would not recommend the routine use of OxZi femoral heads in primary THAs. LEVEL OF EVIDENCE Systematic review and meta-analysis of therapeutic studies I-III.
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Comparative effectiveness of venous thromboembolism prophylaxis options for the patient undergoing total hip and knee replacement: a network meta-analysis.
Kapoor, A, Ellis, A, Shaffer, N, Gurwitz, J, Chandramohan, A, Saulino, J, Ishak, A, Okubanjo, T, Michota, F, Hylek, E, et al
Journal of thrombosis and haemostasis : JTH. 2017;(2):284-294
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UNLABELLED 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.
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Anticoagulants (extended duration) for prevention of venous thromboembolism following total hip or knee replacement or hip fracture repair.
Forster, R, Stewart, M
The Cochrane database of systematic reviews. 2016;(3):CD004179
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BACKGROUND The optimal duration of thromboprophylaxis after total hip or knee replacement, or hip fracture repair remains controversial. It is common practice to administer prophylaxis using low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) until discharge from hospital, usually seven to 14 days after surgery. International guidelines recommend extending thromboprophylaxis for up to 35 days following major orthopaedic surgery but the recommendation is weak due to moderate quality evidence. In addition, recent oral anticoagulants that exert effect by direct inhibition of thrombin or activated factor X lack the need for monitoring and have few known drug interactions. Interest in this topic remains high. OBJECTIVES To assess the effects of extended-duration anticoagulant thromboprophylaxis for the prevention of venous thromboembolism (VTE) in people undergoing elective hip or knee replacement surgery, or hip fracture repair. SEARCH METHODS The Cochrane Vascular Information Specialist searched the Specialised Register (last searched May 2015) and CENTRAL (2015, Issue 4). Clinical trials databases were searched for ongoing or unpublished studies. SELECTION CRITERIA Randomised controlled trials assessing extended-duration thromboprophylaxis (five to seven weeks) using accepted prophylactic doses of LMWH, UFH, vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC) compared with short-duration thromboprophylaxis (seven to 14 days) followed by placebo, no treatment or similar extended-duration thromboprophylaxis with LMWH, UFH, VKA or DOACs in participants undergoing hip or knee replacement or hip fracture repair. DATA COLLECTION AND ANALYSIS We independently selected trials and extracted data. Disagreements were resolved by discussion. We performed fixed-effect model meta-analyses with odds ratios (ORs) and 95% confidence intervals (CIs). We used a random-effects model when there was heterogeneity. MAIN RESULTS We included 16 studies (24,930 participants); six compared heparin with placebo, one compared VKA with placebo, two compared DOAC with placebo, one compared VKA with heparin, five compared DOAC with heparin and one compared anticoagulants chosen at investigators' discretion with placebo. Three trials included participants undergoing knee replacement. No studies assessed hip fracture repair.Trials were generally of good methodological quality. The main reason for unclear risk of bias was insufficient reporting. The quality of evidence according to GRADE was generally moderate, as some comparisons included a single study, low number of events or heterogeneity between studies leading to wide CIs.We showed no difference between extended-duration heparin and placebo in symptomatic VTE (OR 0.59, 95% CI 0.35 to 1.01; 2329 participants; 5 studies; high quality evidence), symptomatic deep vein thrombosis (DVT) (OR 0.73, 95% CI 0.39 to 1.38; 2019 participants; 4 studies; moderate quality evidence), symptomatic pulmonary embolism (PE) (OR 0.61, 95% CI 0.16 to 2.33; 1595 participants; 3 studies; low quality evidence) and major bleeding (OR 0.59, 95% CI 0.14 to 2.46; 2500 participants; 5 studies; moderate quality evidence). Minor bleeding was increased in the heparin group (OR 2.01, 95% CI 1.43 to 2.81; 2500 participants; 5 studies; high quality evidence). Clinically relevant non-major bleeding was not reported.We showed no difference between extended-duration VKA and placebo (one study, 360 participants) for symptomatic VTE (OR 0.10, 95% CI 0.01 to 1.94; moderate quality evidence), symptomatic DVT (OR 0.13, 95% CI 0.01 to 2.62; moderate quality evidence), symptomatic PE (OR 0.32, 95% CI 0.01 to 7.84; moderate quality evidence) and major bleeding (OR 2.89, 95% CI 0.12 to 71.31; low quality evidence). Clinically relevant non-major bleeding and minor bleeding were not reported.Extended-duration DOAC showed reduced symptomatic VTE (OR 0.20, 95% CI 0.06 to 0.68; 2419 participants; 1 study; moderate quality evidence) and symptomatic DVT (OR 0.18, 95% CI 0.04 to 0.81; 2459 participants; 2 studies; high quality evidence) compared to placebo. No differences were found for symptomatic PE (OR 0.25, 95% CI 0.03 to 2.25; 1733 participants; 1 study; low quality evidence), major bleeding (OR 1.00, 95% CI 0.06 to 16.02; 2457 participants; 1 study; low quality evidence), clinically relevant non-major bleeding (OR 1.22, 95% CI 0.76 to 1.95; 2457 participants; 1 study; moderate quality evidence) and minor bleeding (OR 1.18, 95% CI 0.74 to 1.88; 2457 participants; 1 study; moderate quality evidence).We showed no difference between extended-duration anticoagulants chosen at investigators' discretion and placebo (one study, 557 participants, low quality evidence) for symptomatic VTE (OR 0.50, 95% CI 0.09 to 2.74), symptomatic DVT (OR 0.33, 95% CI 0.03 to 3.21), symptomatic PE (OR 1.00, 95% CI 0.06 to 16.13), and major bleeding (OR 5.05, 95% CI 0.24 to 105.76). Clinically relevant non-major bleeding and minor bleeding were not reported.We showed no difference between extended-duration VKA and heparin (one study, low quality evidence) for symptomatic VTE (OR 1.64, 95% CI 0.85 to 3.16; 1279 participants), symptomatic DVT (OR 1.36, 95% CI 0.69 to 2.68; 1279 participants), symptomatic PE (OR 9.16, 95% CI 0.49 to 170.42; 1279 participants), major bleeding (OR 3.87, 95% CI 1.91 to 7.85; 1272 participants) and minor bleeding (OR 1.33, 95% CI 0.64 to 2.76; 1279 participants). Clinically relevant non-major bleeding was not reported.We showed no difference between extended-duration DOAC and heparin for symptomatic VTE (OR 0.70, 95% CI 0.28 to 1.70; 15,977 participants; 5 studies; low quality evidence), symptomatic DVT (OR 0.60, 95% CI 0.11 to 3.27; 15,977 participants; 5 studies; low quality evidence), symptomatic PE (OR 0.91, 95% CI 0.43 to 1.94; 14,731 participants; 5 studies; moderate quality evidence), major bleeding (OR 1.11, 95% CI 0.79 to 1.54; 16,199 participants; 5 studies; high quality evidence), clinically relevant non-major bleeding (OR 1.08, 95% CI 0.90 to 1.28; 15,241 participants; 4 studies; high quality evidence) and minor bleeding (OR 0.95, 95% CI 0.82 to 1.10; 11,766 participants; 4 studies; high quality evidence). AUTHORS' CONCLUSIONS Moderate quality evidence suggests extended-duration anticoagulants to prevent VTE should be considered for people undergoing hip replacement surgery, although the benefit should be weighed against the increased risk of minor bleeding. Further studies are needed to better understand the association between VTE and extended-duration oral anticoagulants in relation to knee replacement and hip fracture repair, as well as outcomes such as distal and proximal DVT, reoperation, wound infection and healing.
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The efficacy and safety of pharmacological prophylaxis of venous thromboembolism following elective knee or hip replacement: systematic review and network meta-analysis.
Cohen, A, Drost, P, Marchant, N, Mitchell, S, Orme, M, Rublee, D, Simon, TA, Sutton, A
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis. 2012;(6):611-27
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The present systematic review was conducted to assess the efficacy and safety of apixaban versus other anticoagulants, for the prevention of venous thromboembolism (VTE) following total hip replacement (THR) and total knee replacement (TKR) surgery. Electronic databases were interrogated to identify relevant randomized controlled trials. A series of direct/indirect comparisons and a network meta-analysis were conducted. Indirect comparisons found that the odds ratio of "all VTE and all-cause death" were significantly higher for dabigatran than for apixaban in patients with THR (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.21) and TKR (OR, 1.72; 95% CI, 1.22-2.42). Rivaroxaban showed similar efficacy to apixaban in patients with THR and TKR (OR, 0.69; 95% CI, 0.38-1.25 and OR, 0.83; 95% CI, 0.57-1.19, respectively). No significant differences were observed in bleeding outcomes between treatments. The novel anticoagulants apixaban, rivaroxaban, and dabigatran demonstrated similar or improved efficacy and similar safety compared with current therapies in this indication.
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Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons.
Gómez-Outes, A, Terleira-Fernández, AI, Suárez-Gea, ML, Vargas-Castrillón, E
BMJ (Clinical research ed.). 2012;:e3675
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OBJECTIVE To analyse clinical outcomes with new oral anticoagulants for prophylaxis against venous thromboembolism after total hip or knee replacement. DESIGN Systematic review, meta-analysis, and indirect treatment comparisons. DATA SOURCES Medline and CENTRAL (up to April 2011), clinical trials registers, conference proceedings, and websites of regulatory agencies. STUDY SELECTION Randomised controlled trials of rivaroxaban, dabigatran, or apixaban compared with enoxaparin for prophylaxis against venous thromboembolism after total hip or knee replacement. Two investigators independently extracted data. Relative risks of symptomatic venous thromboembolism, clinically relevant bleeding, deaths, and a net clinical endpoint (composite of symptomatic venous thromboembolism, major bleeding, and death) were estimated using a random effect meta-analysis. RevMan and ITC software were used for direct and indirect comparisons, respectively. RESULTS 16 trials in 38,747 patients were included. Compared with enoxaparin, the risk of symptomatic venous thromboembolism was lower with rivaroxaban (relative risk 0.48, 95% confidence interval 0.31 to 0.75) and similar with dabigatran (0.71, 0.23 to 2.12) and apixaban (0.82, 0.41 to 1.64). Compared with enoxaparin, the relative risk of clinically relevant bleeding was higher with rivaroxaban (1.25, 1.05 to 1.49), similar with dabigatran (1.12, 0.94 to 1.35), and lower with apixaban (0.82, 0.69 to 0.98). The treatments did not differ on the net clinical endpoint in direct or indirect comparisons. CONCLUSIONS A higher efficacy of new anticoagulants was generally associated with a higher bleeding tendency. The new anticoagulants did not differ significantly for efficacy and safety.