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Acta Neurologica Scandinavica Jan 2022Cerebral venous thrombosis (CVT) is caused by partial or complete occlusion of the major cerebral venous sinuses or the smaller feeding cortical veins which predispose... (Meta-Analysis)
Meta-Analysis Review
Cerebral venous thrombosis (CVT) is caused by partial or complete occlusion of the major cerebral venous sinuses or the smaller feeding cortical veins which predispose to the risk of venous infarction and hemorrhage. Current guidelines recommend treating CVT with either low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH) followed by an oral vitamin K antagonist (VKA) for 3-12 months. Direct oral anticoagulants (DOACs) have already established benefit over warfarin as a long-term treatment of symptomatic venous thromboembolic disorder like deep vein thrombosis (DVT), and pulmonary embolism (PE) given its equal efficacy and better safety profile. The benefit of DOACs over warfarin as a long-term anticoagulation for CVT has likewise been extensively studied, yet it has not been approved as first-line therapy in the current practice. We therefore performed a systematic review and meta-analysis of relevant studies to generate robust evidence regarding the safety and efficacy of DOACs in CVT. This meta-analysis demonstrates that the use of DOACs in CVT has similar efficacy and safety compared to VKAs with better recanalization rate.
Topics: Administration, Oral; Anticoagulants; Heparin; Heparin, Low-Molecular-Weight; Humans; Venous Thromboembolism; Venous Thrombosis
PubMed: 34287841
DOI: 10.1111/ane.13506 -
JAMA Network Open Nov 2022Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited.
OBJECTIVE
To evaluate the safety and outcomes of DOAC reversal agents among patients with ICH.
DATA SOURCES
PubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022.
STUDY SELECTION
The eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded.
DATA EXTRACTION AND SYNTHESIS
Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent.
RESULTS
A total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events.
CONCLUSIONS AND RELEVANCE
In the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.
Topics: Male; Adult; Humans; Aged; Adolescent; Female; Hemorrhage; Retrospective Studies; Anticoagulant Reversal Agents; Anticoagulation Reversal; Anticoagulants; Intracranial Hemorrhages; Thromboembolism
PubMed: 36331504
DOI: 10.1001/jamanetworkopen.2022.40145 -
A systematic review of the efficacy and safety of anticoagulants in advanced chronic kidney disease.Journal of Nephrology Nov 2022Patients with chronic kidney disease (CKD) have an increased risk of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulants have not been studied in... (Review)
Review
BACKGROUND
Patients with chronic kidney disease (CKD) have an increased risk of venous thromboembolism (VTE) and atrial fibrillation (AF). Anticoagulants have not been studied in randomised controlled trials with CrCl < 30 ml/min. The objective of this review was to identify the impact of different anticoagulant strategies in patients with advanced CKD including dialysis.
METHODS
We conducted a systematic review of randomized controlled trials and cohort studies, searching electronic databases from 1946 to 2022. Studies that evaluated both thrombotic and bleeding outcomes with anticoagulant use in CrCl < 50 ml/min were included.
RESULTS
Our initial search yielded 14,503 papers with 53 suitable for inclusion. RCTs comparing direct oral anticoagulants (DOACs) versus warfarin for patients with VTE and CrCl 30-50 ml/min found no difference in recurrent VTE events (RR 0.68(95% CI 0.42-1.11)) with reduced bleeding (RR 0.65 (95% CI 0.45-0.94)). Observational data in haemodialysis suggest lower risk of recurrent VTE and major bleeding with apixaban versus warfarin. Very few studies examining outcomes were available for therapeutic and prophylactic dose low molecular weight heparin for CrCl < 30 ml/min. Findings for patients with AF on dialysis were that warfarin or DOACs had a similar or higher risk of stroke compared to no anticoagulation. For patients with AF and CrCl < 30 ml/min not on dialysis, anticoagulation should be considered on an individual basis, with limited studies suggesting DOACs may have a preferable safety profile.
CONCLUSION
Further studies are still required, some ongoing, in patients with advanced CKD (CrCl < 30 ml/min) to identify the safest and most effective treatment options for VTE and AF.
Topics: Humans; Anticoagulants; Warfarin; Venous Thromboembolism; Administration, Oral; Atrial Fibrillation; Hemorrhage; Renal Insufficiency, Chronic; Heparin, Low-Molecular-Weight
PubMed: 36006608
DOI: 10.1007/s40620-022-01413-x -
Journal of the American College of... Jan 2023The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The efficacy and safety of direct oral anticoagulants (DOACs) for patients with thrombotic antiphospholipid syndrome remain controversial.
OBJECTIVES
The authors performed a systematic review and meta-analysis of randomized controlled trials that compared DOACs with vitamin K antagonists (VKAs).
METHODS
We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials through April 9, 2022. The 2 main efficacy outcomes were a composite of arterial thrombotic events and venous thromboembolic events (VTEs). The main safety outcome was major bleeding. Random effects models with inverse variance were used.
RESULTS
Our search retrieved 253 studies. Four open-label randomized controlled trials involving 472 patients were included (mean control-arm time-in-therapeutic-range 60%). All had proper random sequence generation and adequate allocation concealment. Overall, the use of DOACs compared with VKAs was associated with increased odds of subsequent arterial thrombotic events (OR: 5.43; 95% CI: 1.87-15.75; P < 0.001, I = 0%), especially stroke, and the composite of arterial thrombotic events or VTE (OR: 4.46; 95% CI: 1.12-17.84; P = 0.03, I = 0%). The odds of subsequent VTE (OR: 1.20; 95% CI: 0.31-4.55; P = 0.79, I = 0%), or major bleeding (OR: 1.02; 95% CI: 0.42-2.47; P = 0.97; I = 0%) were not significantly different between the 2 groups. Most findings were consistent within subgroups.
CONCLUSIONS
Patients with thrombotic antiphospholipid syndrome randomized to DOACs compared with VKAs appear to have increased risk for arterial thrombosis. No significant differences were observed between patients randomized to DOACs vs VKAs in the risk of subsequent VTE or major bleeding.
Topics: Humans; Administration, Oral; Anticoagulants; Antiphospholipid Syndrome; Fibrinolytic Agents; Hemorrhage; Randomized Controlled Trials as Topic; Thrombosis; Venous Thromboembolism; Vitamin K
PubMed: 36328154
DOI: 10.1016/j.jacc.2022.10.008 -
Neurocritical Care Jun 2022Our objective was to compare the effectiveness of intravenous and enteral nimodipine in preventing poor outcome from delayed cerebral ischemia in patients with... (Meta-Analysis)
Meta-Analysis Review
Our objective was to compare the effectiveness of intravenous and enteral nimodipine in preventing poor outcome from delayed cerebral ischemia in patients with subarachnoid hemorrhage. We performed a systematic search and a network meta-analysis using the following databases: PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Google Scholar. Risk of Bias 2 tool was used to assess risk of bias of included studies. A ranking among methods was performed on the basis of the frequentist analog of the surface under the cumulative ranking curve. Published studies that met the following population, intervention, comparison, outcomes and study (PICOS) criteria were included: patients with subarachnoid hemorrhage aged 15 years or older (P); nimodipine, intravenous and oral formulation (I); placebo or no intervention (C); poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), case fatality at 3 months, delayed cerebral ischemia, delayed ischaemic neurologic deficit, and vasospasm measured with transcranial Doppler or digital subtraction angiography (O); and randomized controlled trials (S). No language or publication date restrictions were applied. Ten studies were finally included, with a total of 1527 randomly assigned patients. Oral and intravenous nimodipine were both effective in preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. Neither treatment was effective in improving case fatality. Evolving clinical protocols over a 30-year period and the risk of bias of the included studies may limit the strength of our results. Enteral and intravenous nimodipine may have a similar effectiveness in terms of preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. More research may be needed to fully establish the role of intravenous nimodipine in current clinical practice.
Topics: Brain Ischemia; Cerebral Infarction; Humans; Network Meta-Analysis; Nimodipine; Randomized Controlled Trials as Topic; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial
PubMed: 35419702
DOI: 10.1007/s12028-022-01493-4 -
Journal of Clinical Oncology : Official... Jun 2023To conduct an update of the ASCO venous thromboembolism (VTE) guideline.
PURPOSE
To conduct an update of the ASCO venous thromboembolism (VTE) guideline.
METHODS
After publication of potentially practice-changing clinical trials, identified through ASCO's signals approach to updating, an updated systematic review was performed for two guideline questions: perioperative thromboprophylaxis and treatment of VTE. PubMed and the Cochrane Library were searched for randomized controlled trials (RCTs) published between November 1, 2018, and June 6, 2022.
RESULTS
Five RCTs provided information that contributed to changes to the 2019 recommendations. Two RCTs addressed direct factor Xa inhibitors (either rivaroxaban or apixaban) for extended thromboprophylaxis after surgery. Each of these postoperative trials had important limitations but suggested that these two oral anticoagulants are safe and effective in the settings studied. An additional three RCTs addressed apixaban in the setting of VTE treatment. Apixaban was effective in reducing the risk of recurrent VTE, with a low risk of major bleeding.
RECOMMENDATIONS
Apixaban and rivaroxaban were added as options for extended pharmacologic thromboprophylaxis after cancer surgery, with a weak strength of recommendation. Apixaban was also added as an option for the treatment of VTE, with high quality of evidence and a strong recommendation.Additional information is available at www.asco.org/supportive-care-guidelines.
Topics: Humans; Venous Thromboembolism; Rivaroxaban; Anticoagulants; Hemorrhage; Neoplasms
PubMed: 37075273
DOI: 10.1200/JCO.23.00294 -
Future Cardiology May 2022To compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial... (Meta-Analysis)
Meta-Analysis Review
To compare real-world effectiveness/safety of non-vitamin K antagonist oral anticoagulants and vitamin K antagonists among patients with non-valvular atrial fibrillation. A systematic review of electronic databases yielded 7661 citations published from January 2013 to January 2020. Fifty-five studies were included in Bayesian network meta-analyses of hazard ratios. In comparison with vitamin K antagonists, apixaban, dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, ischemic stroke, intracranial hemorrhage and all-cause mortality. Apixaban, dabigatran and edoxaban, but not rivaroxaban, were associated with a reduced risk of major bleeding. This study confirmed the effectiveness and safety of non-vitamin K antagonist oral anticoagulants for the treatment of non-valvular atrial fibrillation in real-world settings, consistent with clinical trial evidence.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Bayes Theorem; Dabigatran; Fibrinolytic Agents; Humans; Network Meta-Analysis; Pyridones; Rivaroxaban; Stroke; Vitamin K
PubMed: 35360925
DOI: 10.2217/fca-2021-0120 -
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 -
Circulation Mar 2024Device-detected atrial fibrillation (also known as subclinical atrial fibrillation or atrial high-rate episodes) is a common finding in patients with an implanted... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Device-detected atrial fibrillation (also known as subclinical atrial fibrillation or atrial high-rate episodes) is a common finding in patients with an implanted cardiac rhythm device and is associated with an increased risk of ischemic stroke. Whether oral anticoagulation is effective and safe in this patient population is unclear.
METHODS
We performed a systematic review of MEDLINE and Embase for randomized trials comparing oral anticoagulation with antiplatelet or no antithrombotic therapy in adults with device-detected atrial fibrillation recorded by a pacemaker, implantable cardioverter defibrillator, cardiac resynchronization therapy device, or implanted cardiac monitor. We used random-effects models for meta-analysis and rated the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation framework (GRADE). The review was preregistered (PROSPERO CRD42023463212).
RESULTS
From 785 citations, we identified 2 randomized trials with relevant clinical outcome data: NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes; 2536 participants) evaluated edoxaban, and ARTESiA (Apixaban for the Reduction of Thrombo-Embolism in Patients With Device-Detected Sub-Clinical Atrial Fibrillation; 4012 participants) evaluated apixaban. Meta-analysis demonstrated that oral anticoagulation with these agents reduced ischemic stroke (relative risk [RR], 0.68 [95% CI, 0.50-0.92]; high-quality evidence). The results from the 2 trials were consistent (I statistic for heterogeneity=0%). Oral anticoagulation also reduced a composite of cardiovascular death, all-cause stroke, peripheral arterial embolism, myocardial infarction, or pulmonary embolism (RR, 0.85 [95% CI, 0.73-0.99]; I=0%; moderate-quality evidence). There was no reduction in cardiovascular death (RR, 0.95 [95% CI, 0.76-1.17]; I=0%; moderate-quality evidence) or all-cause mortality (RR, 1.08 [95% CI, 0.96-1.21]; I=0%; moderate-quality evidence). Oral anticoagulation increased major bleeding (RR, 1.62 [95% CI, 1.05-2.50]; I²=61%; high-quality evidence).
CONCLUSIONS
The results of the NOAH-AFNET 6 and ARTESiA trials are consistent with each other. Meta-analysis of these 2 large randomized trials provides high-quality evidence that oral anticoagulation with edoxaban or apixaban reduces the risk of stroke in patients with device-detected atrial fibrillation and increases the risk of major bleeding.
Topics: Humans; Administration, Oral; Anticoagulants; Atrial Fibrillation; Embolism; Hemorrhage; Ischemic Stroke; Pyridines; Stroke; Thiazoles; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 37952187
DOI: 10.1161/CIRCULATIONAHA.123.067512 -
Shock (Augusta, Ga.) Dec 2021Trauma-induced coagulopathy is associated with very high mortality, and hemorrhage remains the leading preventable cause of death after injury. Directed methods to...
Trauma-induced coagulopathy is associated with very high mortality, and hemorrhage remains the leading preventable cause of death after injury. Directed methods to combat coagulopathy and attain hemostasis are needed. The available literature regarding viscoelastic testing, including thrombelastography (TEG) and rotational thromboelastometry (ROTEM), was reviewed to provide clinically relevant guidance for emergency resuscitation. These tests predict massive transfusion and developing coagulopathy earlier than conventional coagulation testing, within 15 min using rapid testing. They can guide resuscitation after trauma, as well. TEG and ROTEM direct early transfusion of fresh frozen plasma when clinical gestalt has not activated a massive transfusion protocol. Reaction time and clotting time via these tests can also detect clinically significant levels of direct oral anticoagulants. Slowed clot kinetics suggest the need for transfusion of fibrinogen via concentrates or cryoprecipitate. Lowered clot strength can be corrected with platelets and fibrinogen. Finally, viscoelastic tests identify fibrinolysis, a finding associated with significantly increased mortality yet one that no conventional coagulation test can reliably detect. Using these parameters, guided resuscitation begins within minutes of a patient's arrival. A growing body of evidence suggests this approach may improve survival while reducing volumes of blood products transfused.
Topics: Disseminated Intravascular Coagulation; Hemorrhage; Hemostasis; Humans; Resuscitation; Thrombelastography; Wounds and Injuries
PubMed: 33769424
DOI: 10.1097/SHK.0000000000001686