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European Journal of Clinical... Dec 2022This systematic review and meta-analysis aimed to determine whether tramadol intake increases the risk of bleeding in patients receiving oral anticoagulants. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
This systematic review and meta-analysis aimed to determine whether tramadol intake increases the risk of bleeding in patients receiving oral anticoagulants.
METHODS
This systematic review was registered on PROSPERO, CRD42022327230. We searched PubMed and Embase up to 14 April 2022, and references and citations of included studies were screened. Comparative and non-comparative studies exploring bleeding complications among adult patients on oral anticoagulants and tramadol were included. Risk of bias was assessed using an adaptation of the Drug Interaction Probability Scale for case reports and case series and the Newcastle-Ottawa Scale for comparative studies. A meta-analysis was performed for the risk of serious bleeding (leading to hospitalisation or death) associated with tramadol in patients on vitamin K antagonists.
RESULTS
A total of 17 studies were included: 1 case series, 12 case reports, 2 case-control studies and 2 cohort studies. Most of the studies described tramadol-vitamin K antagonists' concomitant use; one case-control study also assessed dabigatran and rivaroxaban; one case report involved dabigatran. Among case reports/series, a total of 33 patients had a bleeding complication while using tramadol and an oral anticoagulant. The 4 comparative studies reported an increased bleeding risk during tramadol and vitamin K antagonist intake which was statistically significant in one study; the pooled risk ratio of serious bleeding was 2.68 [95% CI: 1.45 to 4.96; p < 0.001].
CONCLUSION
This systematic review confirms an association between tramadol use and risk of bleeding in patients on vitamin K antagonists. Evidence is too limited to assess whether this risk extends to patients on direct oral anticoagulants, and further studies are needed.
Topics: Adult; Humans; Dabigatran; Tramadol; Case-Control Studies; Administration, Oral; Anticoagulants; Rivaroxaban; Hemorrhage; Fibrinolytic Agents; Vitamin K; Atrial Fibrillation
PubMed: 36323905
DOI: 10.1007/s00228-022-03411-1 -
The Journal of Arthroplasty Sep 2017Venous thromboembolism causes significant morbidity and mortality in patients after total joint arthroplasty. Although network meta-analyses have demonstrated a benefit... (Meta-Analysis)
Meta-Analysis Review
Low-Molecular-Weight Heparin and the Relative Risk of Surgical Site Bleeding Complications: Results of a Systematic Review and Meta-Analysis of Randomized Controlled Trials of Venous Thromboprophylaxis in Patients After Total Joint Arthroplasty.
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.
Topics: Anticoagulants; Arthroplasty; Arthroplasty, Replacement, Knee; Aspirin; Dabigatran; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Incidence; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Risk; Rivaroxaban; Treatment Outcome; Venous Thromboembolism; Warfarin
PubMed: 28522244
DOI: 10.1016/j.arth.2017.04.010 -
British Journal of Clinical Pharmacology Feb 2022The results of associations between new oral anticoagulants (NOACs) and wound complications after total joint arthroplasty remain inconsistent. We conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
Wound complications and bleeding with new oral anticoagulants in patients undergoing total joint arthroplasty: A systematic review and meta-analysis of randomized controlled trials.
AIMS
The results of associations between new oral anticoagulants (NOACs) and wound complications after total joint arthroplasty remain inconsistent. We conducted a systematic review and meta-analysis of randomized controlled trials to make comparisons with low molecular weight heparins (LMWH) on the clinical outcomes of total wound complications, together with other efficacy and safety endpoints to further evaluate the safety and efficacy of NOACs.
METHODS
This meta-analysis was conducted based on a published protocol (PROSPERO: CRD42019140841). We searched for available articles in PubMed, Embase and Cochrane Library through Jun 62 021. Random-effects meta-analyses, including subgroup analyses, were conducted to estimate the pooled relative risk (RR) and 95% confidence interval (CI) for specific doses of NOACs.
RESULTS
We retrieved 1683 studies, of which 20 were eligible for inclusion. We found that apixaban was associated with a lower incidence of total wound complications compared with LMWH (RR = 0.81; 95% CI: 0.65-1.00), while dabigatran and rivaroxaban did not increase the risk of total wound complications. In addition, apixaban was associated with a reduction in the risk of major/clinically relevant nonmajor bleeding events compared to LMWH (RR = 0.80, 95% CI: 0.65-0.99), while rivaroxaban increased the risk for major/clinically relevant nonmajor bleeding events (RR = 1.23, 95% CI: 1.02-1.50). Moreover, all 4 NOACs were associated with lower incidences of major venous thromboembolism compared with LMWH.
CONCLUSION
A lower risk of wound complications was detected for apixaban, while dabigatran and rivaroxaban did not increase the risk when compared with LMWH. The efficacy of 4 NOACs was broadly similar.
Topics: Administration, Oral; Anticoagulants; Arthroplasty; Dabigatran; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Randomized Controlled Trials as Topic; Rivaroxaban; Venous Thromboembolism
PubMed: 34322914
DOI: 10.1111/bcp.15005 -
Blood Coagulation & Fibrinolysis : An... Oct 2006The objective was to estimate the effect of antithrombin therapy on mortality in disseminated intravascular coagulation (DIC) of severe sepsis and septic shock.... (Review)
Review
The objective was to estimate the effect of antithrombin therapy on mortality in disseminated intravascular coagulation (DIC) of severe sepsis and septic shock. Randomized clinical trials (RCT) on patients with DIC and severe sepsis or septic shock assigned to intravenous antithrombin or placebo were searched. Eligible studies reported death as the outcome measure. Of 35 RCT, 32 trials were excluded because patients were not randomized to antithrombin versus placebo, or no separate data on patients with DIC were given. In three RCT, 364 patients with severe sepsis or septic shock and DIC were randomized. The disease severity, definition of DIC, dose and duration of treatment varied among the trials. In two of the three RCT, data were from subgroup analyses (patients not stratified by DIC). The combined odds ratio for short-term all-cause mortality in those who received antithrombin was 0.649 (95% confidence interval, 0.422-0.998). Data on bleeding complications in patients treated with antithrombin were reported only in one of the RCT and were not considered suitable for systematic safety estimation. In sepsis patients with DIC, administration of antithrombin concentrate may increase overall survival. Current available evidence, however, is not suited to sufficiently inform clinical practice.
Topics: Antithrombins; Disseminated Intravascular Coagulation; Humans; Randomized Controlled Trials as Topic; Sepsis; Shock, Septic; Treatment Outcome
PubMed: 16988545
DOI: 10.1097/01.mbc.0000245302.18010.40 -
Science Progress 2021All cancers can increase the risk of developing venous thromboembolism (VTE), and anticoagulants should be considered as an optimal treatment for patients suffering from... (Meta-Analysis)
Meta-Analysis
All cancers can increase the risk of developing venous thromboembolism (VTE), and anticoagulants should be considered as an optimal treatment for patients suffering from cancer-associated VTE. However, there is still a debate about whether the new oral anticoagulant, rivaroxaban, can bring better efficacy and safety outcomes globally. Thus, this systematic review and meta-analysis was conducted to evaluate the efficacy and safety of rivaroxaban. We searched PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure for relevant published papers before 1 September 2019, with no language restrictions. The primary outcomes are defined as the recurrence of VTE. The secondary outcomes are defined as clinically relevant non-major bleeding, adverse major bleeding events, and all-cause of death. The data were analyzed by Stata with risk ratio (RR) and 95% confidence interval (CI). Four trials encompassing 1996 patients were included. Rivaroxaban reduced recurrent VTE with no significant difference (RR = 0.68, 95% CI = 0.43-1.07). Similarly, there were no significant differences in adverse major bleeding events (RR = 0.86, 95% CI = 0.37-2.00), clinically relevant non-major bleeding (RR = 1.24, 95% CI = 0.73-2.12) and all-cause mortality (RR = 0.76, 95% CI = 0.40-1.44). In a selected study population of cancer patients with VTE, rivaroxaban is as good as other anticoagulants. Further, carefully designed randomized controlled trials should be performed to confirm these results.
Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism
PubMed: 33913387
DOI: 10.1177/00368504211012160 -
World Neurosurgery Sep 2022Management of cerebral venous thrombosis (CVT) involves minimizing expansion of the thrombus and promoting the recanalization of the venous sinus. While current... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Management of cerebral venous thrombosis (CVT) involves minimizing expansion of the thrombus and promoting the recanalization of the venous sinus. While current guidelines include indications of endovascular management and anticoagulation with heparin and warfarin, the use of direct-acting oral anticoagulants (DOACs) has increased. In this study, we aim to conduct a network meta-analysis comparing these 3 therapeutic options: standard anticoagulation, DOACs, and endovascular treatments (EVTs).
METHODS
Seventeen of 2265 studies identified from 4 publication databases met inclusion criteria for this network meta-analysis. Outcomes analyzed included modified Rankin Scale score, complications, mortality, and 6-month recanalization rates using a frequentist network meta-analysis approach. For each outcome, the preferential order of each intervention was ranked hierarchically based on P-score calculations used for frequentist network meta-analyses.
RESULTS
Modified Rankin Scale outcomes were not significantly different based on the type of treatment modality (i.e., standard anticoagulation, DOACs, or EVT). Evaluation of complications demonstrated that patients treated with EVT were significantly more likely to experience a worse outcome than individuals treated with standard anticoagulation (odds ratio [OR] = 1.83, P = 0.04). Other comparisons did not demonstrate a significant difference in adverse events. For all-cause mortality outcomes, EVT demonstrated significantly greater odds of mortality than standard anticoagulation (OR = 1.89, P = 0.02). Mortality between DOACs and standard anticoagulation was not significantly different. When comparing 6-month recanalization rates, DOACs and EVT were significantly more effective than standard anticoagulation (OR = 1.93, OR = 2.2, P < 0.05). EVT followed by DOACs was preferred over standard anticoagulation for 6-month recanalization rates.
CONCLUSIONS
This network meta-analysis evaluates the outcomes in CVT treatment, comparing standard anticoagulation, DOACs, and EVT, with evidence that DOACs have similar outcomes to standard anticoagulation in the treatment of CVT. EVT resulted in an increased risk of overall mortality but improved 6-month recanalization rates.
Topics: Administration, Oral; Anticoagulants; Factor Xa Inhibitors; Heparin; Humans; Intracranial Thrombosis; Network Meta-Analysis; Venous Thrombosis; Warfarin
PubMed: 35688371
DOI: 10.1016/j.wneu.2022.05.142 -
Journal of Clinical Pharmacy and... Feb 2011Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative... (Comparative Study)
Comparative Study Meta-Analysis Review
WHAT IS KNOWN AND OBJECTIVE
Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta-analysis, and adjusted indirect comparison.
METHODS
We searched PubMed, EMBASE, trial registries and regulatory documents through May 2009 for randomized controlled trials (RCTs) of dabigatran (150 and 220 mg daily) and rivaroxaban (10 mg daily) compared with enoxaparin (40-60 mg daily) in elective orthopaedic surgery. We used random effects meta-analysis to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI) for the outcomes of total venous thromboembolism, VTE (deep venous thrombosis, non-fatal pulmonary embolism and all-cause mortality), and haemorrhagic adverse events (major and clinically relevant non-major bleeds). Adjusted indirect comparison was used for the pooled RRs of dabigatran and rivaroxaban with enoxaparin as the common control.
RESULTS
Rivaroxaban was superior to enoxaparin for the prevention of venous thromoboembolism (RR 0.56, 95% CI 0.43-0.73, P<0.0001), with a trend for increased haemorrhage (RR 1.26, 95% CI 0.94-1.69, P=0.13). Dabigatran was not superior to enoxaparin for prevention of VTE (RR 1.12, 95% 0.97-1.29, P=0.12), and did not reduce haemorrhage risk (RR 1.10, 95% 0.90-1.35, P=0.32). Adjusted indirect comparison showed that rivaroxaban was superior to dabigatran in preventing VTE, RR 0.50 (95% CI 0.37-0.68), but with a slight trend towards increased haemorrhage RR 1.14 (95% CI 0.80-1.64).
WHAT IS NEW AND CONCLUSION
Rivaroxaban may be more effective than dabigatran for prevention of VTE after elective orthopaedic surgery but might also slightly increase the risk of haemorrhage.
Topics: Anticoagulants; Antithrombins; Benzimidazoles; Dabigatran; Enoxaparin; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; beta-Alanine
PubMed: 21198726
DOI: 10.1111/j.1365-2710.2010.01162.x -
British Journal of Clinical Pharmacology Nov 2022The evidence of a protective effect of proton-pump inhibitor (PPI) in oral anticoagulant (OAC)-treated patients against gastrointestinal bleeding (GIB) is still lacking.... (Meta-Analysis)
Meta-Analysis Review
AIMS
The evidence of a protective effect of proton-pump inhibitor (PPI) in oral anticoagulant (OAC)-treated patients against gastrointestinal bleeding (GIB) is still lacking. We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI cotherapy.
METHODS
A systematic search of PubMed, EMBASE, Cochrane and Scopus databases was performed for studies reporting GIB risk in OAC and PPI cotherapy. Primary outcomes were total GIB and major GIB events. Pooled estimates of GIB risk were calculated by a random-effect meta-analysis and reported as odds ratios and 95% confidence interval.
RESULTS
A total of 10 studies and 1 970 931 patients were included. OAC and PPI cotherapy were associated with a lower odds of total and major GIB; odds ratio (95% confidence interval) was 0.67 (0.62-0.74) for total and 0.68 (0.63-0.75) for major GIB, respectively. No differences in the GIB of PPI cotherapy were observed between Asians and non-Asians (P-for-difference, total GIB = .70, major GIB = .75, respectively). For all kinds of OAC except for edoxaban, PPI cotreatment was related to lower odds of GIB by 24-44%. The protective effect of PPI on total GIB was more significant in concurrent antiplatelets or nonsteroidal anti-inflammatory drug users and those with high bleeding risks: patients with previous GIB history, HAS-BLED ≥3 or underlying gastrointestinal diseases.
CONCLUSION
In patients who receive OAC, PPI cotherapy is associated with a lower total and major GIB irrespective of ethnic group and OAC type, except for edoxaban. PPI cotherapy can be considered particularly in patients with high risk of GIB.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Gastrointestinal Hemorrhage; Humans; Proton Pump Inhibitors; Pyridines; Thiazoles
PubMed: 35921204
DOI: 10.1111/bcp.15478 -
BMJ (Clinical Research Ed.) Aug 2013To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety outcomes of oral anticoagulants and antiplatelet drugs in the secondary prevention of venous thromboembolism: systematic review and network meta-analysis.
OBJECTIVE
To summarise and compare the efficacy and safety of various oral anticoagulants (dabigatran, rivaroxaban, apixaban, and vitamin K antagonists) and antiplatelet agents (acetylsalicylic acid) for the secondary prevention of venous thromboembolism.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Literature search using Medline (1950 to present), Embase (1980 to present), and the Cochrane Register of Controlled Trials using the OVID interface. Publications from potentially relevant journals were also searched by hand.
REVIEW METHODS
Randomised controlled trials of patients receiving anticoagulants, antiplatelet drugs, or placebo or observation for secondary prevention of venous thromboembolism. Selected outcomes were rates of recurrent venous thromboembolism and major bleeding. Two reviewers independently extracted data onto standardised forms.
RESULTS
12 articles met our inclusion criteria, with 11,999 patients evaluated for efficacy and 12,167 for safety. All treatments reduced the risk of recurrent venous thromboembolism. Compared with placebo or observation, vitamin K antagonists at a standard adjusted dose (target international normalised ratio 2.0-3.0) showed the highest risk difference (odds ratio 0.07; 95% credible interval 0.03 to 0.15) and acetylsalicylic acid showed the lowest risk difference (0.65; 0.39 to 1.03). Risk of major bleeding was higher with a standard adjusted dose of vitamin K antagonists (5.24; 1.78 to 18.25) than with placebo or observation. Fatal recurrent venous thromboembolism and fatal bleeding were rare. Detailed subgroup and individual patient level data were not available.
CONCLUSIONS
All oral anticoagulants and antiplatelet agents investigated in this analysis were associated with a reduced recurrence of venous thromboembolism compared with placebo or observation, although acetylsalicylic acid was associated with the lowest risk reduction. Vitamin K antagonists given at a standard adjusted dose was associated with the greatest risk reduction in recurrent venous thromboembolism, but also the greatest risk of major bleeding.
Topics: Anticoagulants; Aspirin; Benzimidazoles; Dabigatran; Hemorrhage; Humans; Morpholines; Platelet Aggregation Inhibitors; Pyrazoles; Pyridones; Recurrence; Rivaroxaban; Thiophenes; Venous Thromboembolism; Vitamin K; beta-Alanine
PubMed: 23996149
DOI: 10.1136/bmj.f5133 -
Renal Failure Dec 2024This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis.
METHODS
All types of studies published on PubMed, Embase, CENTRAL, and Web of Science up to 10 September 2023 and comparing outcomes of apixaban vs. VKA in dialysis patients were eligible.
RESULTS
Two randomized controlled trials (RCTs) and six retrospective studies were included. Apixaban treatment was associated with significantly lower risk of major bleeding (RR: 0.61; 95% CI: 0.48, 0.77; = 50%) and clinically relevant non-major bleeding (RR: 0.82, 95% CI: 0.68, 0.98, = 9%) compared to VKA. Meta-analysis also showed that the risk of gastrointestinal bleeding (RR: 0.74, 95% CI: 0.64, 0.85, = 16%) and intracranial bleeding (RR: 0.64, 95% CI: 0.49, 0.84, = 0%) was significantly reduced with apixaban. Meta-analysis showed no difference in the risk of ischemic stroke (RR: 0.40, 95% CI: 0.06, 2.69, = 0%), mortality (RR: 1.26, 95% CI: 0.74, 2.16, = 94%) and recurrent venous thromboembolism (RR: 1.02, 95% CI: 0.87, 1.21, = 0%) between the two groups. Subgroup analysis of RCTs showed no difference in bleeding outcomes.
CONCLUSIONS
Low-quality evidence from a mix of RCTs and retrospective studies shows that apixaban may have better safety and equivalent efficacy as compared to VKA in dialysis patients. Apixaban treatment correlated with significantly reduced risk of major bleeding and clinically relevant nonmajor bleeding in observational studies but not in RCTs. The predominance of retrospective data warrants caution in the interpretation of results.
Topics: Humans; Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Pyrazoles; Pyridones; Randomized Controlled Trials as Topic; Renal Dialysis; Vitamin K
PubMed: 38770962
DOI: 10.1080/0886022X.2024.2349114