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Journal of Hematology & Oncology May 2022International clinical practice guidelines have progressively endorsed direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparins (LMWHs)... (Meta-Analysis)
Meta-Analysis
Direct oral anticoagulant versus low molecular weight heparin for the treatment of cancer-associated venous thromboembolism: 2022 updated systematic review and meta-analysis of randomized controlled trials.
International clinical practice guidelines have progressively endorsed direct oral anticoagulants (DOACs) as an alternative to low-molecular-weight heparins (LMWHs) monotherapy for the initial and long-term treatment of cancer-associated thrombosis (CAT). Several new randomized controlled trials (RCTs) have recently reported additional results on the safety and efficacy of DOACs in this setting. We performed an updated meta-analysis of all publicly available data from RCTs comparing DOACs with LMWHs for the treatment of CAT. Six RCTs enrolling 3690 patients with CAT were included. Compared with LMWHs, DOACs significantly decreased the risk of CAT recurrence (RR, 0.67; 95%CI, 0.52-0.85), with a non-significant increase in the risk of major bleeding (RR, 1.17; 95%CI, 0.82-1.67), a significant increase in the risk of clinically relevant nonmajor bleeding (RR 1.66; 95%CI, 1.31-2.09) and no difference in all-cause mortality rates. These results increase the level of certainty of available evidence supporting the use of DOACs as an effective and safe option for the treatment of CAT in selected cancer patients.
Topics: Anticoagulants; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism
PubMed: 35598026
DOI: 10.1186/s13045-022-01289-1 -
Stroke Jan 2018The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
The use of oral anticoagulant therapy for stroke prevention in atrial fibrillation has been transformed by the availability of the nonvitamin K antagonist oral anticoagulants. Real-world studies on the use of nonvitamin K antagonist oral anticoagulants would help elucidate their effectiveness and safety in daily clinical practice. Apixaban was the third nonvitamin K antagonist oral anticoagulants introduced to clinical practice, and increasing real-world studies have been published. Our aim was to summarize current evidence about real-world studies on apixaban for stroke prevention in atrial fibrillation.
METHODS
We performed a systematic review and meta-analysis of all observational real-world studies comparing apixaban with other available oral anticoagulant drugs.
RESULTS
From the original 9680 results retrieved, 16 studies have been included in the final meta-analysis. Compared with warfarin, apixaban regular dose was more effective in reducing any thromboembolic event (odds ratio: 0.77; 95% confidence interval: 0.64-0.93), but no significant difference was found for stroke risk. Apixaban was as effective as dabigatran and rivaroxaban in reducing thromboembolic events and stroke. The risk of major bleeding was significantly lower for apixaban compared with warfarin, dabigatran, and rivaroxaban (relative risk reduction, 38%, 35%, and 46%, respectively). Similarly, the risk for intracranial hemorrhage was significantly lower for apixaban than warfarin and rivaroxaban (46% and 54%, respectively) but not dabigatran. The risk of gastrointestinal bleeding was lower with apixaban when compared with all oral anticoagulant agents (<0.00001 for all comparisons).
CONCLUSIONS
Use of apixaban in real-life is associated with an overall similar effectiveness in reducing stroke and any thromboembolic events when compared with warfarin. A better safety profile was found with apixaban compared with warfarin, dabigatran, and rivaroxaban.
Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Female; Humans; Intracranial Hemorrhages; Male; Polymers; Pyrazoles; Pyridones; Risk Factors; Rivaroxaban; Saliva, Artificial; Stroke; Vitamin K; Warfarin
PubMed: 29167388
DOI: 10.1161/STROKEAHA.117.018395 -
ASAIO Journal (American Society For... Mar 2021Extracorporeal membrane oxygenation (ECMO) causes both thrombosis and bleeding. Major society guidelines recommend continuous, systemic anticoagulation to prevent...
Extracorporeal membrane oxygenation (ECMO) causes both thrombosis and bleeding. Major society guidelines recommend continuous, systemic anticoagulation to prevent thrombosis of the ECMO circuit, though this may be undesirable in those with active, or high risk of, bleeding. We aimed to systematically review thrombosis and bleeding outcomes in published cases of adults treated with ECMO without continuous systemic anticoagulation. Ovid MEDLINE, Cochrane CENTRAL and CDSR, and hand search via SCOPUS were queried. Eligible studies were independently reviewed by two blinded authors if they reported adults (≥18 years) treated with either VV- or VA-ECMO without continuous systemic anticoagulation for ≥24 hours. Patient demographics, clinical data, and specifics of ECMO technology and treatment parameters were collected. Primary outcomes of interest included incidence of bleeding, thrombosis of the ECMO circuit requiring equipment exchange, patient venous or arterial thrombosis, ability to wean off of ECMO, and mortality. Of the 443 total publications identified, 34 describing 201 patients met our inclusion criteria. Most patients were treated for either acute respiratory distress syndrome or cardiogenic shock. The median duration of anticoagulant-free ECMO was 4.75 days. ECMO circuity thrombosis and patient thrombosis occurred in 27 (13.4%) and 19 (9.5%) patients, respectively. Any bleeding and major or "severe" bleeding was reported in 66 (32.8%) and 56 (27.9%) patients, respectively. Forty patients (19%) died. While limited by primarily retrospective data and inconsistent reporting of outcomes, our systematic review of anticoagulant-free ECMO reveals an incidence of circuity and patient thrombosis comparable to patients receiving continuous systemic anticoagulation while on ECMO.
Topics: Adult; Anticoagulants; Extracorporeal Membrane Oxygenation; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Retrospective Studies; Thrombosis
PubMed: 33627603
DOI: 10.1097/MAT.0000000000001230 -
American Journal of Hematology Jul 2021The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
The effectiveness and safety of non-heparin anticoagulants for the treatment of heparin-induced thrombocytopenia (HIT) are not fully established, and the optimal treatment strategy is unknown. In a systematic review and meta-analysis, we aimed to determine precise rates of platelet recovery, new or progressive thromboembolism (TE), major bleeding, and death for all non-heparin anticoagulants and to study potential sources of variability.
METHODS
Following a detailed protocol (PROSPERO: CRD42020219027), EMBASE and Medline were searched for all studies reporting clinical outcomes of patients treated with non-heparin anticoagulants (argatroban, danaparoid, fondaparinux, direct oral anticoagulants [DOAC], bivalirudin, and other hirudins) for acute HIT. Proportions of patients with the outcomes of interest were pooled using a random-effects model for each drug. The influence of the patient population, the diagnostic test used, the study design, and the type of article was assessed.
RESULTS
Out of 3194 articles screened, 92 studies with 119 treatment groups describing 4698 patients were included. The pooled rates of platelet recovery ranged from 74% (bivalirudin) to 99% (fondaparinux), TE from 1% (fondaparinux) to 7% (danaparoid), major bleeding from 1% (DOAC) to 14% (bivalirudin), and death from 7% (fondaparinux) to 19% (bivalirudin). Confidence intervals were mostly overlapping, and results were not influenced by patient population, diagnostic test used, study design, or type of article.
DISCUSSION
Effectiveness and safety outcomes were similar among various anticoagulants, and significant factors affecting these outcomes were not identified. These findings support fondaparinux and DOACs as viable alternatives to conventional anticoagulants for treatment of acute HIT in clinical practice.
Topics: Anticoagulants; Blood Platelets; Hemorrhage; Heparin; Humans; Thrombocytopenia; Thromboembolism; Treatment Outcome
PubMed: 33857342
DOI: 10.1002/ajh.26194 -
The Cochrane Database of Systematic... Apr 2023Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review. OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence). For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence). AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortality. DOACs reduced the rate of major bleeding compared to conventional anticoagulation. The certainty of evidence was moderate or high.
Topics: Humans; Anticoagulants; Antithrombins; Factor Xa Inhibitors; Rivaroxaban; Dabigatran; Venous Thromboembolism; Neoplasm Recurrence, Local; Venous Thrombosis; Pulmonary Embolism; Hemorrhage
PubMed: 37058421
DOI: 10.1002/14651858.CD010956.pub3 -
BMJ (Clinical Research Ed.) Jul 2022To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital.
DESIGN
Systematic review and network meta-analysis.
DATA SOURCES
Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital.
MAIN OUTCOME MEASURES
Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework.
RESULTS
44 randomised controlled trials that randomly assigned 90 095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses.
CONCLUSIONS
Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020173088.
Topics: Anticoagulants; Bayes Theorem; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Hospitals; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism
PubMed: 35788047
DOI: 10.1136/bmj-2022-070022 -
The Cochrane Database of Systematic... Jan 2022It is generally assumed by practitioners and guideline authors that combined modalities (methods of treatment) are more effective than single modalities in preventing... (Review)
Review
BACKGROUND
It is generally assumed by practitioners and guideline authors that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thromboembolism (VTE), defined as deep vein thrombosis (DVT) or pulmonary embolism (PE), or both. This is the second update of the review first published in 2008.
OBJECTIVES
The aim of this review was to assess the efficacy of combined intermittent pneumatic leg compression (IPC) and pharmacological prophylaxis compared to single modalities in preventing VTE.
SEARCH METHODS
The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and AMED databases, and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 18 January 2021. We searched the reference lists of relevant articles for additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) or controlled clinical trials (CCTs) of combined IPC and pharmacological interventions used to prevent VTE compared to either intervention individually.
DATA COLLECTION AND ANALYSIS
We independently selected studies, applied Cochrane's risk of bias tool, and extracted data. We resolved disagreements 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. We assessed the certainty of the evidence using GRADE. The outcomes of interest were PE, DVT, bleeding and major bleeding.
MAIN RESULTS
We included a total of 34 studies involving 14,931 participants, mainly undergoing surgery or admitted with trauma. Twenty-five studies were RCTs (12,672 participants) and nine were CCTs (2259 participants). Overall, the risk of bias was mostly unclear or high. We used GRADE to assess the certainty of the evidence and this was downgraded due to the risk of bias, imprecision or indirectness. The addition of pharmacological prophylaxis to IPC compared with IPC alone reduced the incidence of symptomatic PE from 1.34% (34/2530) in the IPC group to 0.65% (19/2932) in the combined group (OR 0.51, 95% CI 0.29 to 0.91; 19 studies, 5462 participants, low-certainty evidence). The incidence of DVT was 3.81% in the IPC group and 2.03% in the combined group showing a reduced incidence of DVT in favour of the combined group (OR 0.51, 95% CI 0.36 to 0.72; 18 studies, 5394 participants, low-certainty evidence). The addition of pharmacological prophylaxis to IPC, however, increased the risk of any bleeding compared to IPC alone: 0.95% (22/2304) in the IPC group and 5.88% (137/2330) in the combined group (OR 6.02, 95% CI 3.88 to 9.35; 13 studies, 4634 participants, very low-certainty evidence). Major bleeding followed a similar pattern: 0.34% (7/2054) in the IPC group compared to 2.21% (46/2079) in the combined group (OR 5.77, 95% CI 2.81 to 11.83; 12 studies, 4133 participants, very low-certainty evidence). Tests for subgroup differences between orthopaedic and non-orthopaedic surgery participants were not possible for PE incidence as no PE events were reported in the orthopaedic subgroup. No difference was detected between orthopaedic and non-orthopaedic surgery participants for DVT incidence (test for subgroup difference P = 0.19). The use of combined IPC and pharmacological prophylaxis modalities compared with pharmacological prophylaxis alone reduced the incidence of PE from 1.84% (61/3318) in the pharmacological prophylaxis group to 0.91% (31/3419) in the combined group (OR 0.46, 95% CI 0.30 to 0.71; 15 studies, 6737 participants, low-certainty evidence). The incidence of DVT was 9.28% (288/3105) in the pharmacological prophylaxis group and 5.48% (167/3046) in the combined group (OR 0.38, 95% CI 0.21 to 0.70; 17 studies; 6151 participants, high-certainty evidence). Increased bleeding side effects were not observed for IPC when it was added to anticoagulation (any bleeding: OR 0.87, 95% CI 0.56 to 1.35, 6 studies, 1314 participants, very low-certainty evidence; major bleeding: OR 1.21, 95% CI 0.35 to 4.18, 5 studies, 908 participants, very low-certainty evidence). No difference was detected between the orthopaedic and non-orthopaedic surgery participants for PE incidence (test for subgroup difference P = 0.82) or for DVT incidence (test for subgroup difference P = 0.69).
AUTHORS' CONCLUSIONS
Evidence suggests that combining IPC with pharmacological prophylaxis, compared to IPC alone reduces the incidence of both PE and DVT (low-certainty evidence). Combining IPC with pharmacological prophylaxis, compared to pharmacological prophylaxis alone, reduces the incidence of both PE (low-certainty evidence) and DVT (high-certainty evidence). We downgraded due to risk of bias in study methodology and imprecision. Very low-certainty evidence suggests that the addition of pharmacological prophylaxis to IPC increased the risk of bleeding compared to IPC alone, a side effect not observed when IPC is added to pharmacological prophylaxis (very low-certainty evidence), as expected for a physical method of thromboprophylaxis. The certainty of the evidence for bleeding was downgraded to very low due to risk of bias in study methodology, imprecision and indirectness. The results of this update agree with current guideline recommendations, which support the use of combined modalities in hospitalised people (limited to those with trauma or undergoing surgery) at risk of developing VTE. More studies on the role of combined modalities in VTE prevention are needed to provide evidence for specific patient groups and to increase our certainty in the evidence.
Topics: Anticoagulants; Hemorrhage; Humans; Leg; Pulmonary Embolism; Venous Thromboembolism
PubMed: 35089599
DOI: 10.1002/14651858.CD005258.pub4 -
Critical Care (London, England) Jan 2019Regional citrate anticoagulation (RCA) is a widely used strategy for continuous renal replacement therapy (CRRT). Most of the current guidelines recommend liver failure... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Regional citrate anticoagulation (RCA) is a widely used strategy for continuous renal replacement therapy (CRRT). Most of the current guidelines recommend liver failure as one of the contraindications for citrate anticoagulation. However, some studies suggested that the use of citrate for CRRT in liver failure patients did not increase the risk of citrate-related complications. The purpose of this systematic review is to summarize the current evidences on the safety and efficacy of RCA for CRRT in liver failure patients.
METHODS
We performed a comprehensive search on PubMed, Embase, and the Cochrane Library databases from the inception to March 1, 2018. Studies enrolled adult (age > 18 years) patients with various levels of liver dysfunction underwent RCA-CRRT were included in this systematic review.
RESULTS
After the study screening, 10 observational studies with 1241 liver dysfunction patients were included in this systematic review. The pooled rate of citrate accumulation and bleeding was 12% [3%, 22%] and 5% [2%, 8%], respectively. Compared with the baseline data, the serum pH, bicarbonate, and base excess (BE), the rate of metabolic alkalosis, the serum ionized calcium (ionCa) and total calcium (totCa) level, and the ratio of total calcium/ionized calcium (totCa/ionCa) significantly increased at the end of observation. However, no significant increase was observed in serum citrate (MD - 65.82 [- 194.19, 62.55]), lactate (MD 0.49 [- 0.27, 1.26]) and total bilirubin concentration (MD 0.79 [- 0.70, 2.29]) at the end of CRRT. Compared with non-liver failure patients, the live failure patients showed no significant difference in the pH (MD - 0.04 [- 0.13, 0.05]), serum lactate level (MD 0.69 [- 0.26, 1.64]), and totCa/ionCa ratio (MD 0.03 [- 0.12, 0.18]) during CRRT. The median of mean filter lifespan was 55.9 h, with a range from 22.7 to 72 h.
CONCLUSIONS
Regional citrate anticoagulation seems to be a safe anticoagulation method in liver failure patients underwent CRRT and could yield a favorable filter lifespan. Closely monitoring the acid base status and electrolyte balance may be more necessary during RCA-CRRT in patients with liver failure.
Topics: Acid-Base Equilibrium; Adult; Anticoagulants; Citric Acid; Hemorrhage; Humans; Liver Failure; Renal Replacement Therapy
PubMed: 30678706
DOI: 10.1186/s13054-019-2317-9 -
BMJ Clinical Evidence Mar 2011Deep venous thrombosis (DVT) or pulmonary embolism may occur in almost 2 in 1000 people each year, with up to 25% of those having a recurrence. Around 5% to 15% of... (Review)
Review
INTRODUCTION
Deep venous thrombosis (DVT) or pulmonary embolism may occur in almost 2 in 1000 people each year, with up to 25% of those having a recurrence. Around 5% to 15% of people with untreated DVT may die from pulmonary embolism. Risk factors for DVT include immobility, surgery (particularly orthopaedic), malignancy, pregnancy, older age, and inherited or acquired prothrombotic clotting disorders.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for proximal DVT? What are the effects of treatments for isolated calf DVT? What are the effects of treatments for pulmonary embolism? What are the effects of interventions on oral anticoagulation management in people with thromboembolism? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 45 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: anticoagulation; compression stockings; low molecular weight heparin (short and long term, once or twice daily, and home treatment); oral anticoagulants (short and long term, high intensity, abrupt discontinuation, and computerised decision support); prolonged duration of anticoagulation; thrombolysis; vena cava filters; and warfarin.
Topics: Administration, Oral; Animals; Anticoagulants; Heparin, Low-Molecular-Weight; Humans; Pulmonary Embolism; Thromboembolism; Venous Thrombosis; Warfarin
PubMed: 21385473
DOI: No ID Found -
Journal of the American College of... Jun 2021Direct oral anticoagulants (DOACs) have shown a positive benefit-risk balance in both clinical trials and real-world data, but approximately 2% to 3.5% of patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct oral anticoagulants (DOACs) have shown a positive benefit-risk balance in both clinical trials and real-world data, but approximately 2% to 3.5% of patients experience major bleeding annually. Many of these patients require hospitalization, and the administration of reversal agents may be required to control bleeding.
OBJECTIVES
The aim of this study was to investigate clinical outcomes associated with the use of 4-factor prothrombin complex concentrates, idarucizumab, or andexanet for reversal of severe DOAC-associated bleeding.
METHODS
The investigators systematically searched for studies of reversal agents for the treatment of severe bleeding associated with DOAC. Mortality rates, thromboembolic events, and hemostatic efficacy were meta-analyzed using a random effects model.
RESULTS
The investigators evaluated 60 studies in 4,735 patients with severe DOAC-related bleeding who were treated with 4-factor prothrombin complex concentrates (n = 2,688), idarucizumab (n = 1,111), or andexanet (n = 936). The mortality rate was 17.7% (95% confidence interval [CI]: 15.1% to 20.4%), and it was higher in patients with intracranial bleedings (20.2%) than in patients with extracranial hemorrhages (15.4%). The thromboembolism rate was 4.6% (95% CI: 3.3% to 6.0%), being particularly high with andexanet (10.7%; 95% CI: 6.5% to 15.7%). The effective hemostasis rate was 78.5% (95% CI: 75.1% to 81.8%) and was similar regardless of the reversal agent considered. The rebleeding rate was 13.2% (95% CI: 5.5% to 23.1%) and 78% of rebleeds occurred after resumption of anticoagulation. The risk of death was markedly and significantly associated with failure to achieve effective hemostasis (relative risk: 3.63; 95% CI: 2.56 to 5.16). The results were robust regardless of the type of study or the hemostatic scale used.
CONCLUSIONS
The risk of death after severe DOAC-related bleeding remains significant despite a high rate of effective hemostasis with reversal agents. Failure to achieve effective hemostasis strongly correlated with a fatal outcome. Thromboembolism rates are particularly high with andexanet. Comparative clinical trials are needed.
Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Blood Coagulation; Blood Coagulation Factors; Factor Xa; Hemorrhage; Hemostasis; Humans; Recombinant Proteins; Retrospective Studies
PubMed: 34140101
DOI: 10.1016/j.jacc.2021.04.061