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Journal of the American Pharmacists... 2021Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer after disease progression. Thus, timely initiation of anticoagulation after... (Review)
Review
BACKGROUND
Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer after disease progression. Thus, timely initiation of anticoagulation after diagnosis of a VTE is required to prevent significant sequelae. Direct oral anticoagulants (DOACs) are newer anticoagulant options for cancer associated VTE (CA-VTE), which historically has been treated with low molecular weight heparin.
OBJECTIVE
The objective of this study was to review the available literature evaluating the use of apixaban for CA-VTE.
METHODS
A systematic review (following PRISMA Guidelines) of MEDLINE and EMBASE using the search terms "apixaban" AND "cancer" AND "VTE" was performed from database inception through May 20, 2020. Articles were eligible for inclusion if they were full articles fulfilling the following criteria: (1) randomized controlled trial (RCT) or prospective cohort study, or (2) subgroup analysis of an RCT, and (3) reported clinical outcomes associated with apixaban for prevention or treatment of VTE in patients with cancer.
RESULTS
A total of 532 articles were identified. After duplicates were removed, 423 articles were screened, and 12 articles were eligible for full-text review. Of the 12 articles, 2 were excluded for having no comparator group, and 2 were excluded for being abstracts only. Ultimately, 8 articles met the inclusion criteria.
CONCLUSIONS
The available literature supports the safety and efficacy of apixaban for the treatment and prevention of CA-VTE. With the recent publication of the CARAVAGGIO trial, we anticipate that apixaban will be uniformly recommended in national guidelines as a treatment option for CA-VTE.
Topics: Administration, Oral; Anticoagulants; Humans; Neoplasms; Pyrazoles; Pyridones; Venous Thromboembolism
PubMed: 34229946
DOI: 10.1016/j.japh.2021.06.005 -
Chest Feb 2015Direct oral anticoagulants (DOAs) have been shown to be as effective and at least as safe as conventional anticoagulation for the prevention of recurrences in patients... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Direct oral anticoagulants (DOAs) have been shown to be as effective and at least as safe as conventional anticoagulation for the prevention of recurrences in patients with VTE. Whether this is the case in patients with cancer-associated VTE remains undefined.
METHODS
We performed a meta-analysis of randomized controlled trials with the aim of assessing the efficacy and safety of DOAs in patients with VTE and cancer. MEDLINE, EMBASE, and CENTRAL were searched up to December 2013 with no language restriction. The primary outcome of the analysis was recurrent VTE. Data on major bleeding (MB) and clinically relevant nonmajor bleeding were analyzed. Data were pooled and compared by ORs and 95% CIs.
RESULTS
Overall, 10 studies comparing DOAs with conventional anticoagulation for treatment of VTE including patients with cancer were included in the review. Six studies were included in the meta-analysis (two with dabigatran, two with rivaroxaban, one with edoxaban, and one with apixaban), accounting for a total of 1,132 patients. VTE recurred in 23 of 595 (3.9%) and in 32 of 537 (6.0%) patients with cancer treated with DOAs and conventional treatment, respectively (OR, 0.63; 95% CI, 0.37-1.10; I2, 0%). MB occurred in 3.2% and 4.2% of patients receiving DOAs and conventional treatment, respectively (OR, 0.77; 95% CI, 0.41-1.44; I2, 0%).
CONCLUSIONS
DOAs seem to be as effective and safe as conventional treatment for the prevention of VTE in patients with cancer. Further clinical trials in patients with cancer-associated VTE should be performed to confirm these results.
Topics: Anticoagulants; Antithrombins; Factor Xa Inhibitors; Heparin; Humans; Neoplasms; Recurrence; Venous Thromboembolism; Vitamin K
PubMed: 25211264
DOI: 10.1378/chest.14-0402 -
Current Problems in Cardiology Nov 2022Patients with cancer are at higher risk of atrial fibrillation (AF). Currently there are no definitive data on clinical outcomes for nonvitamin K antagonist oral... (Meta-Analysis)
Meta-Analysis Review
Efficacy and Safety of the Non-Vitamin K Antagonist Oral Anticoagulant Among Patients With Nonvalvular Atrial Fibrillation and Cancer: A Systematic Review and Network Meta-analysis.
Patients with cancer are at higher risk of atrial fibrillation (AF). Currently there are no definitive data on clinical outcomes for nonvitamin K antagonist oral anticoagulant (NOACs) and warfarin in cancer patients with AF. Therefore, we conducted a meta-analysis to evaluate the efficacy and safety of NOACs compared with warfarin. A search through Pubmed/MEDLINE, Embase, and Cochrane library was done from the databases inception to March 2022. Studies that compared NOACs to warfarin in the setting of AF and cancer were included. The primary outcomes were the incidence of major bleeding and ischemic stroke/systemic embolism (SE). Secondary outcomes were major adverse cardiovascular event (MACE), intracranial bleeding, and Major gastrointestinal bleeding. Risk ratios (RRs) with 95% confidence intervals (CI) were used to report the outcomes. A total of 11 studies were included. We found that NOACs were associated with a lower incidence of major bleeding and combined ischemic stroke/SE in patients with AF and cancer compared with warfarin (RR 0.57; 95% CI 0.44-0.75, P < 0.0001 and RR 0.59; 95% CI 0.47-0.75, P < 0.0001, respectively). Also, there was lower incidence of Intracranial and major gastrointestinal bleeding in patients who received NOACs compared with warfarin (P < 0.0001). Network analyses revealed that apixaban and dabigatran were associated with reduction of major bleeding compared with warfarin. Among patients who diagnosed with AF and cancer, NOACs were associated with lower incidence of major bleeding ischemic stroke/SE compared with warfarin. Furthermore, NOACs were associated with lower gastrointestinal and intracranial bleeding.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Gastrointestinal Hemorrhage; Humans; Ischemic Stroke; Neoplasms; Network Meta-Analysis; Stroke; Treatment Outcome; Warfarin
PubMed: 35932849
DOI: 10.1016/j.cpcardiol.2022.101346 -
Journal of Vascular Surgery Jul 2019The direct thrombin inhibitor bivalirudin (BIV) was shown to be superior to unfractionated heparin (UFH) in percutaneous coronary interventions for reducing procedural... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The direct thrombin inhibitor bivalirudin (BIV) was shown to be superior to unfractionated heparin (UFH) in percutaneous coronary interventions for reducing procedural blood loss. The aim of this study was to compare outcome profiles of BIV and UFH in peripheral endovascular procedures (PEPs) by synthesizing the currently available data.
METHODS
Following the PRISMA statement, we conducted a comprehensive literature search using Medline, Cochrane CENTRAL, PubMed, EMBASE, CINAHL Google scholar, and clinicaltrials.gov. We recruited randomized, controlled trials and well-conducted observational studies that compared UFH and BIV in PEPs requiring anticoagulation, excluding endovascular cardiac procedures and coronary interventions. Random-effects meta-analyses were conducted to compare the outcome profiles of these two agents.
RESULTS
Thirteen articles containing 14 studies involving a total of 21,057 patients were enrolled. Of these, 2 were randomized controlled trials, 2 were prospective cohort studies, and 10 were retrospective studies. There were no significant differences between BIV and UFH in terms of procedural success rates, major and minor perioperative bleeding, transfusion, perioperative transient ischemic attack, or hemorrhagic strokes. However, compared with UFH, BIV had significantly lower odds ratios (OR) of perioperative mortality (OR, 0.58; 95% confidence interval [CI], 0.40-0.86), major adverse cardiovascular events (OR, 0.65; 95% CI, 0.51-0.83), net adverse clinical events (OR, 0.75; 95% CI, 0.63-0.88), perioperative myocardial infarction (OR, 0.73; 95% CI, 0.55-0.98), major vascular complications (OR, 0.59; 95% CI, 0.39-0.91), and minor vascular complications (OR, 0.58; 95% CI, 0.40-0.84).
CONCLUSIONS
Compared with UFH, PEPs using BIV had comparable procedural success rates and odds of perioperative transient ischemic attack and hemorrhagic stroke. However, procedures with BIV had a lower but nonsignificant odds of perioperative bleeding and transfusion. Depending on the procedures conducted, the patients who received BIV will have reduced or comparable odds of perioperative mortality, myocardial infarction, major adverse cardiovascular events, net adverse clinical events, and major and minor vascular complications. Therefore, BIV may be chosen solely as an alternative procedural anticoagulant to UFH for PEPs.
Topics: Anticoagulants; Antithrombins; Endovascular Procedures; Hemorrhage; Heparin; Hirudins; Humans; Ischemic Attack, Transient; Myocardial Infarction; Observational Studies as Topic; Patient Safety; Peptide Fragments; Peripheral Vascular Diseases; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Risk Factors; Stroke; Treatment Outcome
PubMed: 31230646
DOI: 10.1016/j.jvs.2018.12.037 -
Clinical Drug Investigation Apr 2021Rivaroxaban and apixaban are direct oral anticoagulants increasing in popularity as convenient alternatives to warfarin. However, current guidelines recommend against...
BACKGROUND AND OBJECTIVE
Rivaroxaban and apixaban are direct oral anticoagulants increasing in popularity as convenient alternatives to warfarin. However, current guidelines recommend against use in patients with a BMI > 40 kg/m or bodyweight > 120 kg unless drug-specific levels are measured, which may not be feasible across all clinical practices. Accordingly, the objective of this study was to broadly examine literature evaluating the clinical outcomes of rivaroxaban and/or apixaban in patients with increased body mass.
METHODS
A systematic literature review (guided by PRISMA) was performed through January 27, 2021 using PubMed, Embase, and Scopus. Key search term clusters included drug and weight-related concepts (overweight/obese, body mass index [BMI], waist circumference). DistillerSR was utilized to review and process search results. Studies met inclusion if they analyzed the risk of bleeding and/or thrombosis in patients with increased body mass (i.e., via BMI or other criteria) receiving rivaroxaban or apixaban. Clinical guidelines, case reports/series, pharmacokinetic/dynamic analyses, and commentaries were excluded. Bias was examined qualitatively across studies.
RESULTS
After duplicates were removed, the original search rendered 1822 abstracts and 200 full-texts for screening, ultimately providing a final set of 24 studies for qualitative review. Of these studies, 13 (54.2%) enabled comparisons between patients of increased versus normal body mass, while 11 (45.8%) reported outcomes only for patients of increased body mass. The working definition of 'increased body mass' varied amongst the studies, including 11 (45.8%) studies that utilized BMI, seven (29.2%) with a combination of BMI and body measurement, two (8.3%) that relied on body weight alone, and four (16.7%) that identified obesity-related ICD codes. All 13 comparative studies found similar or reduced rates of safety and efficacy outcomes with rivaroxaban and apixaban.
CONCLUSION
The literature reports similar or lower bleeding and thrombotic risk for rivaroxaban and apixaban in patients of increased body mass compared to patients of normal body mass. Future prospective controlled studies are needed to further define guidelines for use in this population.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Body Mass Index; Hemorrhage; Humans; Pyrazoles; Pyridones; Rivaroxaban; Warfarin
PubMed: 33677803
DOI: 10.1007/s40261-021-01019-4 -
International Journal of Hematology Oct 2017To prevent thromboembolic events associated with heparin-induced thrombocytopenia (HIT), patients usually are treated with argatroban, lepirudin, and bivalirudin. Here,... (Comparative Study)
Comparative Study Meta-Analysis Review
To prevent thromboembolic events associated with heparin-induced thrombocytopenia (HIT), patients usually are treated with argatroban, lepirudin, and bivalirudin. Here, we conducted a meta-analysis of studies to comparing the treatment of HIT with the following direct thrombin inhibitor: argatroban versus lepirudin and argatroban versus bivalirudin. We systematically searched PubMed, Embase, and Cochrane Library database for relevant studies. The clinical outcomes were thromboembolic complication and bleeding. A total of 589 articles were found and 9 of which were finally included in this meta-analysis. There were no significantly differences of thromboembolic complication between argatroban and hirudin analogues (lepirudin and bivalirudin) in the treatment of HIT (lepirudin: RR = 0.773, 95% CI = 0.449-1.331, P = 0.353; bivalirudin: RR = 0.768, 95% CI = 0.386-1.527, P = 0.452). Moreover, the incidence of clinical bleeding of argatroban was similar to hirudin analogues (lepirudin: RR = 0.755, 95% CI = 0.531-1.073, P = 0.117; bivalirudin: RR = 0.995, 95% CI = 0.673-1.472, P = 0.981). Current evidences show that argatroban has the similar effectiveness and safety with lepirudin and bivalirudin for defending against HIT.
Topics: Arginine; Female; Heparin; Hirudins; Humans; Male; Pipecolic Acids; Recombinant Proteins; Sulfonamides; Thrombocytopenia
PubMed: 28600720
DOI: 10.1007/s12185-017-2271-8 -
Critical Care (London, England) Dec 2012Data from interventional trials of systemic anticoagulation for sepsis inconsistently suggest beneficial effects in case of acute lung injury (ALI). Severe systemic... (Review)
Review
BACKGROUND
Data from interventional trials of systemic anticoagulation for sepsis inconsistently suggest beneficial effects in case of acute lung injury (ALI). Severe systemic bleeding due to anticoagulation may have offset the possible positive effects. Nebulization of anticoagulants may allow for improved local biological availability and as such may improve efficacy in the lungs and lower the risk of systemic bleeding complications.
METHOD
We performed a systematic review of preclinical studies and clinical trials investigating the efficacy and safety of nebulized anticoagulants in the setting of lung injury in animals and ALI in humans.
RESULTS
The efficacy of nebulized activated protein C, antithrombin, heparin and danaparoid has been tested in diverse animal models of direct (for example, pneumonia-, intra-pulmonary lipopolysaccharide (LPS)-, and smoke inhalation-induced lung injury) and indirect lung injury (for example, intravenous LPS- and trauma-induced lung injury). Nebulized anticoagulants were found to have the potential to attenuate pulmonary coagulopathy and frequently also inflammation. Notably, nebulized danaparoid and heparin but not activated protein C and antithrombin, were found to have an effect on systemic coagulation. Clinical trials of nebulized anticoagulants are very limited. Nebulized heparin was found to improve survival of patients with smoke inhalation-induced ALI. In a trial of critically ill patients who needed mechanical ventilation for longer than two days, nebulized heparin was associated with a higher number of ventilator-free days. In line with results from preclinical studies, nebulization of heparin was found to have an effect on systemic coagulation, but without causing systemic bleedings.
CONCLUSION
Local anticoagulant therapy through nebulization of anticoagulants attenuates pulmonary coagulopathy and frequently also inflammation in preclinical studies of lung injury. Recent human trials suggest nebulized heparin for ALI to be beneficial and safe, but data are very limited.
Topics: Acute Lung Injury; Administration, Inhalation; Animals; Anticoagulants; Humans; Nebulizers and Vaporizers
PubMed: 22546487
DOI: 10.1186/cc11325 -
The Lancet. Gastroenterology &... Feb 2017Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin.
METHODS
For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs).
FINDINGS
We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47-1·08]; warfarin vs dabigatran 0·88 [0·59-1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42-2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20-1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07-0.76]) or dabigatran (0.24 [0.07-0.77]).
INTERPRETATION
Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with warfarin or low-molecular-weight heparin. These findings support the continued use of direct oral anticoagulants.
FUNDING
Leeds Teaching Hospitals Charitable Foundation.
Topics: Administration, Oral; Anticoagulants; Dabigatran; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Network Meta-Analysis; Risk Factors; Warfarin
PubMed: 28403994
DOI: 10.1016/S2468-1253(16)30162-5 -
European Journal of Clinical... Aug 2023Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to non-major bleeding, which may lead to stroke recurrence. We... (Meta-Analysis)
Meta-Analysis Review
Non-major bleeding risk of direct oral anticoagulants versus vitamin K antagonists for stroke prevention with atrial fibrillation: a systematic review and network meta-analysis.
BACKGROUND
Direct oral anticoagulants (DOACs) are associated with bleeding. Patients often stop taking DOACs due to non-major bleeding, which may lead to stroke recurrence. We aimed to determine the risk of non-major bleeding using different DOACs to prevent strokes in atrial fibrillation (AF).
METHODS
A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting non-major bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated.
RESULTS
Nineteen randomized controlled trials (RCTs) (involving 85,826 patients) were included. For clinically relevant non-major bleeding, the risk for bleeding was lowest for apixaban (SUCRA, 93.9), followed by that for VKAs (SUCRA, 47.7), dabigatran (SUCRA, 40.3), rivaroxaban (SUCRA, 35.9), and edoxaban (SUCRA, 32.2). The minor bleeding safety of DOACs was ranked from highest to lowest as follows: apixaban (SUCRA, 78.1), edoxaban (SUCRA, 69.4), dabigatran (SUCRA, 48.8), and VKAs (SUCRA, 3.7).
CONCLUSIONS
Based on current evidence, for stroke prevention in patients with AF, the safest DOAC is apixaban in terms of non-major bleeding. This suggests that apixaban may have a lower risk of non-major bleeding than other anticoagulants and may help provide some clinical reference for choosing a more appropriate drug for the patient.
Topics: Humans; Atrial Fibrillation; Dabigatran; Network Meta-Analysis; Anticoagulants; Hemorrhage; Stroke; Rivaroxaban; Fibrinolytic Agents; Vitamin K; Administration, Oral
PubMed: 37310479
DOI: 10.1007/s00228-023-03520-5 -
American Journal of Cardiovascular... Aug 2015The non-vitamin K antagonist oral anticoagulants (NOACs) overcame some limitations of vitamin K antagonists (VKAs), and are at least as effective in stroke prevention,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The non-vitamin K antagonist oral anticoagulants (NOACs) overcame some limitations of vitamin K antagonists (VKAs), and are at least as effective in stroke prevention, with an additional decrease of intracranial bleeding risk. The transferability of these benefits to the real world requires tolerability (related to adverse events) and acceptability (drug discontinuation) profiles at least similar to VKAs.
METHODS
We performed a systematic review with meta-analysis of randomized controlled trials (RCTs) evaluating NOACs versus VKAs in patients with non-valvular atrial fibrillation (AF). Studies were searched in April 2015 through MEDLINE, the Cochrane Collaboration's Database, Health Technology Assessment (HTA), Web of Science, and regulatory agencies' documents. Serious adverse events (SAEs) as well as drug-related and patient-related discontinuation rates were the outcomes of interest. Random-effects meta-analysis was performed, and the results expressed as risk ratios (RRs) and 95 % confidence intervals (CIs). Heterogeneity was evaluated with I (2) test.
RESULTS
Five RCTs evaluating four NOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) and 72,720 patients were included. Overall, NOACs were associated with a 4 % risk reduction of SAEs (95 % CI 2-6; I (2) = 0 %). Drug-related and patient-related discontinuation rates were similar between NOACs and VKAs (RR 1.03 [0.88-1.21] and RR 0.99 [0.89-1.10], respectively). Significant heterogeneity (I (2) ≥ 75 %) was found among studies results, which could be, at least partially, explained by the findings of the open-label dabigatran trial.
CONCLUSIONS
NOACs were associated with a small, yet significant, risk reduction of SAEs in patients with AF. NOACs' drug-related and patient-related acceptability profiles were similar to those for VKAs. The results were heterogeneous mainly because of the increased rate of discontinuation associated with dabigatran. Pragmatic trials and cohort studies should be conducted to further address these important clinical questions.
Topics: Antithrombins; Atrial Fibrillation; Blood Coagulation; Dabigatran; Humans; Intracranial Hemorrhages; Pharmacovigilance; Randomized Controlled Trials as Topic; Stroke
PubMed: 26091633
DOI: 10.1007/s40256-015-0132-5