1.
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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Abstract
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 Clinical trials databases were searched for ongoing or unpublished studies.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.
2.
Meta-analysis of continuous oral anticoagulants versus heparin bridging in patients undergoing CIED surgery: reappraisal after the BRUISE study.
Sant'anna, RT, Leiria, TL, Nascimento, T, Sant'anna, JR, Kalil, RA, Lima, GG, Verma, A, Healey, JS, Birnie, DH, Essebag, V
Pacing and clinical electrophysiology : PACE. 2015;(4):417-23
Abstract
BACKGROUND Management of patients treated with oral anticoagulation (OAC) requiring a cardiovascular implantable electronic device (CIED) surgery is a challenge that requires balancing the risk of bleeding complications with the risk of thromboembolic events. Recently the approach of performing these procedures while the patient remains with a therapeutic international normalized ratio has gained interest due to several publications showing its relative safety. OBJECTIVES To evaluate the safety and effectiveness of continuous use of OAC compared with heparin bridging in the perioperative setting of CIED surgery using a meta-analysis. METHODS A systematic review of PubMed/MEDLINE, Ovid, and Elsevier databases was performed. Eligible randomized controlled trials and cohort studies were included. The outcomes studied were risk of clinically significant bleeding and of thromboembolic events. Our analysis was restricted to OAC with vitamin K antagonists. RESULTS Of 560 manuscripts initially considered relevant, seven were included in the meta-analysis, totaling 2,191 patients. Data are reported as odds ratios (ORs) with confidence interval (CI) of 95%. Maintenance of OAC was associated with a significantly lower risk of postoperative bleeding compared with heparin bridge (OR = 0.25, 95% CI 0.17-0.36, P < 0.00001). There was no difference noted in the risk of thromboembolic events between the two strategies (OR = 1.86, 95% CI 0.29-12.17, P = 0.57). CONCLUSIONS Uninterrupted use of OAC in the perioperative of CIED surgery was associated with a reduced risk of bleeding. This strategy should be considered the preferred one in patients at moderate-to-high risk of thromboembolic events.
3.
Flushing the central venous catheter: is heparin necessary?
Dal Molin, A, Allara, E, Montani, D, Milani, S, Frassati, C, Cossu, S, Tonella, S, Brioschi, D, Rasero, L
The journal of vascular access. 2014;(4):241-8
Abstract
PURPOSE The aim of this systematic review was to assess the efficacy of heparin flushing in the lock of central venous catheters. METHODS We searched MEDLINE and CINAHL databases. Eligible studies were randomized controlled trials evaluating the use of heparin versus normal saline or other solution in the flushing of central catheter among adult patients. No language restrictions were applied. Two reviewers independently screened titles and abstracts in order to identify relevant publications. The same two reviewers retrieved and evaluated full texts. Parameter estimates regarding catheter occlusion were pooled using network meta-analysis with Bayesian hierarchical modeling. RESULTS We identified 462 references. Eight studies were included. There was no evidence that heparin was more effective than normal saline in reducing occlusions. It was unclear whether urokinase and lepirudin were more effective than heparin in reducing occlusions. Vitamin C solution does not appear to prolong catheter patency. CONCLUSIONS There is no evidence of a different effectiveness between heparin flushing and normal saline or other solutions in reducing catheter occlusions. Due to the little and inconclusive evidence available in this field, further studies might be necessary.
4.
Citrate versus unfractionated heparin for anticoagulation in continuous renal replacement therapy.
Liao, YJ, Zhang, L, Zeng, XX, Fu, P
Chinese medical journal. 2013;(7):1344-9
Abstract
BACKGROUND Unfractionated heparin is the most commonly used anticoagulant in continuous renal replacement therapy (CRRT), but it can increase the risk of bleeding. Citrate is a promising substitute. Our study was to assess the efficacy and safety of citrate versus unfractionated heparin in CRRT. METHODS We searched the MEDLINE, the EMBASE, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure Database until up to November 2011 for randomized controlled trials comparing citrate with unfractionated heparin in adult patients with acute kidney injury prescribed CRRT. The primary outcome was mortality and the secondary outcomes included circuit survival, control of uremia, risk of bleeding, transfusion rates, acid-base statuses, and disturbance of sodium and calcium homeostasis. RESULTS Four trials met the inclusion criteria. Meta-analysis found no significant difference between two anticoagulants on mortality. Less bleeding and more hypocalcemic episodes were with citrate. Citrate was superior or comparable to unfractionated heparin in circuit life. CONCLUSIONS Citrate anticoagulation in CRRT seems to be superior in reducing bleeding risk and with a longer or similar circuit life, although there is more metabolic derangement. Mortality superiority has not been approved.