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Annals of Palliative Medicine Jul 2021To evaluate the efficacy and safety of Xa inhibitors in patients with heart failure (HF) and coronary artery disease (CAD) or peripheral artery disease (PAD). (Meta-Analysis)
Meta-Analysis
Efficacy and safety of Xa inhibitors in patients with heart failure and coronary or peripheral artery disease: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
To evaluate the efficacy and safety of Xa inhibitors in patients with heart failure (HF) and coronary artery disease (CAD) or peripheral artery disease (PAD).
METHODS
A systematic electronic literature search was performed using the PubMed, Web of Science, EMBASE, and Cochrane Library databases from inception to June 26, 2019. A total of four randomized controlled trials involving 14,694 patients were included in this meta-analysis.
RESULTS
The meta-analysis showed that there was no statistical difference between the Xa inhibitor and control group regarding the primary efficacy outcome [rivaroxaban 2.5 mg group: relative risk (RR) 0.82, 95% CI: 0.66-1.01, P=0.06; rivaroxaban 5 mg group: RR 0.86, 95% CI: 0.73-1.02, P=0.08]. The risk of the primary safety outcome was significantly increased among patients who received Xa inhibitors compared with the control group (rivaroxaban 2.5 mg group: RR 1.55, 95% CI: 1.21-1.98, P=0.0006; rivaroxaban 5 mg group: RR 1.66, 95% CI: 1.30-2.12, P<0.0001). There was no significant difference in the risk of cardiovascular death between the Xa inhibitor and control group (rivaroxaban 2.5 mg group: RR 0.79, 95% CI: 0.54-1.14, P=0.21; rivaroxaban 5 mg group: RR 0.89, 95% CI: 0.73-1.08, P=0.24). The risk of myocardial infarction (MI) in the rivaroxaban 5 mg group was significantly lower than that of the control group (RR 0.83, 95% CI: 0.69-0.99, P=0.04). However, the risk of MI in the rivaroxaban 2.5 mg group was similar to that of the control group (RR 0.85, 95% CI: 0.71-1.01, P=0.07).
DISCUSSION
Xa inhibitors were associated with a higher risk of major adverse cardiovascular events and bleeding among HF and CAD or PAD patients. Therefore, Xa inhibitors should be used cautiously in patients with HF and CAD or PAD.
Topics: Factor Xa Inhibitors; Heart Failure; Humans; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Rivaroxaban
PubMed: 34353093
DOI: 10.21037/apm-21-1645 -
Clinical and Applied... 2022Direct Oral Anticoagulants (DOACs) , which partially replace warfarin, have been developed as a safe and effective therapy for patients with stable coronary artery... (Meta-Analysis)
Meta-Analysis
Direct Oral Anticoagulants (DOACs) , which partially replace warfarin, have been developed as a safe and effective therapy for patients with stable coronary artery disease (SCAD) and atrial fibrillation (AF). However, the choice of DOACs and warfarin remains controversial. We conducted a network meta-analysis (NMA) using randomized controlled trials (RCTs) through a systematic literature review to evaluate the the efficacy and safety of DOACs in SCAD and AF patients. Five RCTs with 6524 patients were included. The results showed that patients taking DOACs had a lower risk of stroke/systemic embolism (OR, 0.64; 95% CI, 0.54-0.76, < .00001, = 89%), intracranial bleeding (OR, 0.41; 95% CI, 0.26-0.64, = .0001, = 0%), major bleeding (OR, 0.98; 95% CI, 0.81-1.148, = .80, = 88%), and all-cause mortality (OR, 1.04; 95% CI, 0.88-1.22, = .66, = 51%) than those taking warfarin. Compared to warfarin, rivaroxaban (20 mg, once/day) was more advantageous in preventing stroke/systemic embolism, as was apixaban (5 mg or 2.5 mg, twice/day) in reducing major bleeding (OR, 0.79; 95% CI, 0.48-1.3) and all-cause mortality (OR, 0.97; 95% CI, 0.69-1.4). Different doses of DOACs showed obvious advantages against intracranial hemorrhage, without significant differences. Thus, DOACs have more effective than warfarin in clinical efficacy and safety.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Embolism; Hemorrhage; Humans; Network Meta-Analysis; Rivaroxaban; Stroke; Warfarin
PubMed: 36198012
DOI: 10.1177/10760296221131033 -
Blood Sep 2020Direct oral anticoagulants (DOACs) are an emerging treatment option for patients with cancer and acute venous thromboembolism (VTE), but studies have reported... (Meta-Analysis)
Meta-Analysis
Direct oral anticoagulants (DOACs) are an emerging treatment option for patients with cancer and acute venous thromboembolism (VTE), but studies have reported inconsistent results. This systematic review and meta-analysis compared the efficacy and safety of DOACs and low-molecular-weight heparins (LMWHs) in these patients. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and conference proceedings were searched to identify relevant randomized controlled trials. Additional data were obtained from the original authors to homogenize definitions for all study outcomes. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Other outcomes included the composite of recurrent VTE and major bleeding, clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Summary relative risks (RRs) were calculated in a random effects meta-analysis. In the primary analysis comprising 2607 patients, the risk of recurrent VTE was nonsignificantly lower with DOACs than with LMWHs (RR, 0.68; 95% CI, 0.39-1.17). Conversely, the risks of major bleeding (RR, 1.36; 95% CI, 0.55-3.35) and CRNMB (RR, 1.63; 95% CI, 0.73-3.64) were nonsignificantly higher. The risk of the composite of recurrent VTE or major bleeding was nonsignificantly lower with DOACs than with LMWHs (RR, 0.86; 95% CI, 0.60-1.23). Mortality was comparable in both groups (RR, 0.96; 95% CI, 0.68-1.36). Findings were consistent during the on-treatment period and in those with incidental VTE. In conclusion, DOACs are an effective treatment option for patients with cancer and acute VTE, although caution is needed in patients at high risk of bleeding.
Topics: Anticoagulants; Factor Xa Inhibitors; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Neoplasms; Treatment Outcome; Venous Thromboembolism
PubMed: 32396939
DOI: 10.1182/blood.2020005819 -
Value in Health Regional Issues Jan 2023Several studies have evaluated the economic evaluation of a group of medications known as novel oral anticoagulant drugs (NOACs) in recent years. The aim of this study...
OBJECTIVES
Several studies have evaluated the economic evaluation of a group of medications known as novel oral anticoagulant drugs (NOACs) in recent years. The aim of this study is to review and systematically analyze the cost-utility studies results of warfarin compared with other NOAC drugs in atrial fibrillation patients.
METHODS
A systematic review was performed to identify all studies evaluating the NOAC medications in comparison with warfarin. For this purpose, PubMed, Cochrane Library, ISI Web of Science, and Scopus were searched from 2013 to 2022. Articles were independently screened with inclusion criteria, and full texts were reviewed. First, the Consolidated Health Economic Evaluation Reporting Standards checklist was used to evaluate the quality of the articles. Then, the costs and outcomes of the studies were analyzed, and findings were appraised critically.
RESULTS
A total of 84 costs-per-quality-adjusted life-year (QALY) cases were extracted from the studies in which the share of rivaroxaban, edoxaban, apixaban, and dabigatran were 31%, 13%, 29%, and 27%, respectively. The median cost per QALY of rivaroxaban, edoxaban, apixaban, and dabigatran was 21 910$/QALY, 22 096$/QALY, 17 765$/QALY, and 24 161$/QALY, respectively. Subgroup analysis based on perspective showed that dabigatran had the highest incremental cost-effectiveness ratio (ICER) and edoxaban had the lowest ICER value. Edoxaban and apixaban had the highest and the lowest cost per QALY from an insurance perspective, respectively.
CONCLUSION
Despite the differences and variations in the economic evaluation studies of NOAC drugs, these drugs have shown acceptable cost-effectiveness in developed and developing countries. Among NOAC drugs, apixaban has the lowest ICER and the highest cost-effectiveness.
Topics: Humans; Anticoagulants; Warfarin; Atrial Fibrillation; Rivaroxaban; Dabigatran; Cost-Benefit Analysis; Administration, Oral; Stroke
PubMed: 36402007
DOI: 10.1016/j.vhri.2022.09.006 -
Journal of the American Heart... Jul 2019Background Several studies have investigated the effect of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer, but the... (Meta-Analysis)
Meta-Analysis
Background Several studies have investigated the effect of non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients with cancer, but the results remain controversial. Therefore, we conducted a meta-analysis to compare the efficacy and safety of NOACs versus warfarin in this population. Methods and Results We systematically searched the PubMed and Embase databases until February 16, 2019 for studies comparing the effect of NOACs with warfarin in AF patients with cancer. Risk ratios (RRs) with 95% CIs were extracted and pooled by a random-effects model. Five studies involving 8908 NOACs and 12 440 warfarin users were included. There were no significant associations between cancer status and risks of stroke or systemic embolism, major bleeding, or death in AF patients. Compared with warfarin, NOACs were associated with decreased risks of stroke or systemic embolism (RR, 0.52; 95% CI, 0.28-0.99), venous thromboembolism (RR, 0.37, 95% CI, 0.22-0.63), and intracranial or gastrointestinal bleeding (RR, 0.65; 95% CI, 0.42-0.98) and with borderline significant reductions in ischemic stroke (RR, 0.63; 95% CI, 0.40-1.00) and major bleeding (RR, 0.73; 95% CI, 0.53-1.00). In addition, risks of efficacy and safety outcomes of NOACs versus warfarin were similar between AF patients with and without cancer. Conclusions In patients with AF and cancer, compared with warfarin, NOACs had lower or similar rates of thromboembolic and bleeding events and posed a reduced risk of venous thromboembolism.
Topics: Anticoagulants; Atrial Fibrillation; Dabigatran; Embolism; Factor Xa Inhibitors; Gastrointestinal Hemorrhage; Hemorrhage; Humans; Intracranial Hemorrhages; Neoplasms; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Stroke; Thiazoles; Venous Thromboembolism; Warfarin
PubMed: 31310583
DOI: 10.1161/JAHA.119.012540 -
Cardiovascular Therapeutics 2022Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Rivaroxaban and apixaban are the most widely used nonvitamin K oral anticoagulants (NOACs) in patients with venous thromboembolism (VTE). This meta-analysis evaluates the effectiveness and safety of both NOACs versus standard of care (SoC) in real-world practice.
METHODS
Real-world evidence (RWE) studies were identified through a systematic literature review conducted between January 2012 and July 2020, using Embase, MEDLINE, and the websites of cardiological, hematological, and oncological associations. Eligible RWE studies recruited adult patients with deep vein thrombosis and/or pulmonary embolism and presented a comparison between rivaroxaban and apixaban versus SoC, consisting either of vitamin K antagonists, heparins, or combinations thereof. Hazard ratios (HRs) for the comparison between NOACs and SoC were extracted from the relevant studies or estimated based on the reported binary data. The between-treatment contrasts were reported as HRs with associated 95% confidence intervals.
RESULTS
A total of 65 RWE studies were identified and considered relevant for the meta-analysis. Compared with SoC, both rivaroxaban and apixaban were associated with reduced risks of recurrent VTE and a lower rate of major bleeding events. Patients treated with rivaroxaban were at a lower risk of all-cause death compared with those receiving SoC (HR = 0.56 [0.39-0.80]), while evidence for apixaban from the identified studies was insufficient to demonstrate a statistically significant change in mortality (HR = 0.66 [0.30-1.47]).
CONCLUSION
This analysis indicates that in real-world practice, rivaroxaban and apixaban are associated with a lower risk of recurrent VTE and major bleeding events compared with SoC. Survival benefit in patients treated with rivaroxaban was also observed.
Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thromboembolism
PubMed: 35801133
DOI: 10.1155/2022/2756682 -
BMJ Open Feb 2021Current guidelines do not recommend direct oral anticoagulants (DOACs) to treat cerebral venous thrombosis (CVT) despite their benefits over standard therapy. We...
OBJECTIVES
Current guidelines do not recommend direct oral anticoagulants (DOACs) to treat cerebral venous thrombosis (CVT) despite their benefits over standard therapy. We performed a systematic review to summarise the published experience of DOAC therapy in CVT.
DATA SOURCES
MEDLINE, Embase and COCHRANE databases up to 18 November 2020.
ELIGIBILITY CRITERIA
All published articles of patients with CVT treated with DOAC were included. Studies without follow-up information were excluded.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers screened articles and extracted data. A risk of bias analysis was performed.
PRIMARY AND SECONDARY OUTCOME MEASURES
Safety data included mortality, intracranial haemorrhage (ICH) or other adverse events. Efficacy data included recurrent CVT, recanalisation rates and disability by modified Rankin Scales (mRS).
RESULTS
33 studies met inclusion criteria. One randomised controlled trial, 5 observational cohorts and 27 case series or studies reported 279 patients treated with DOAC for CVT: 41% dabigatran, 47% rivaroxaban, 10% apixaban and 2% edoxaban, in addition to 315 patients treated with standard therapy. The observational cohorts showed a similar risk of death in DOAC and standard therapy arms (RR 2.12, 95% CI 0.29 to 15.59). New ICH was reported in 2 (0.7%) DOAC-treated patients and recurrent CVT occurred in 4 (1.5%). A favourable mRS between 0 and 2 was reported in 94% of DOAC-treated patients, more likely than standard therapy in observational cohorts (RR 1.13, 95% CI 1.02 to 1.25).
CONCLUSION
The evidence for DOAC use in CVT is limited although suggests sufficient safety and efficacy despite variability in timing and dose of treatment. This systematic review highlights that further rigorous trials are needed to validate these findings and to determine optimal treatment regimens.
Topics: Administration, Oral; Anticoagulants; Dabigatran; Hemorrhage; Humans; Venous Thrombosis
PubMed: 33593766
DOI: 10.1136/bmjopen-2020-040212 -
European Review For Medical and... Aug 2021To compare the outcomes between direct-acting oral anticoagulants and vitamin K antagonists, particularly for risk of stroke and bleeding, among patients with atrial... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of outcomes of direct-acting oral anticoagulants vs. vitamin K antagonists in patients with bioprosthetic heart valves or valve repair: a systematic review and meta-analysis.
OBJECTIVE
To compare the outcomes between direct-acting oral anticoagulants and vitamin K antagonists, particularly for risk of stroke and bleeding, among patients with atrial fibrillation (AF) and bioprosthetic heart valve replacement or repair.
MATERIALS AND METHODS
A systematic search was conducted in the PubMed, Scopus, Cochrane Database of Systematic Reviews and Google scholar databases. Studies that were done in patients with AF who underwent bioprosthetic heart valve replacement or repair and that compared the outcomes between the use of direct-acting oral anticoagulants (DOACs) and vitamin K antagonists were eligible for inclusion. Studies that were preferably randomized controlled trials or adopted a cohort approach or retrospective data-based studies were considered for inclusion. The strength of association was presented in the form of pooled hazards risk (HR). Statistical analysis was done using STATA version 16.0.
RESULTS
A total of 8 articles were included in the meta-analysis. There were no significant differences in the risk of "all-cause stroke" [HR 0.72, 95% CI: 0.39, 1.34] and ischemic stroke [HR 0.79, 95% CI: 0.49, 1.29] between the two groups. The risk of "any bleeding" [HR 0.74, 95% CI: 0.64, 0.87], major bleeding [HR 0.60, 95% CI: 0.42, 0.86] and intra-cranial bleeding [HR 0.54, 95% CI: 0.36, 0.81] was much lower in those that received DOAC compared to warfarin. Compared to those receiving warfarin, those on DOACs had substantially reduced risk of any clinical thromboembolic events [HR 0.52, 95% CI: 0.39, 0.70]. No significant differences were noted for all-cause mortality [HR 0.88, 95% CI: 0.74, 1.05], cardiovascular events/myocardial infarction (MI) [HR 0.58, 95% CI: 0.33, 1.04] and and readmission rates [HR 0.85, 95% CI: 0.62, 1.18].
CONCLUSIONS
Findings suggest that the use DOACs in patients with AF with bioprosthetic valve replacement or repair is comparatively better than vitamin K antagonists in reducing the risk of bleeding and thrombo-embolic events. Future studies with a randomized design and larger sample sizes are needed to further substantiate these findings.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Heart Valves; Humans; Vitamin K
PubMed: 34355372
DOI: 10.26355/eurrev_202108_26457 -
Journal of Medical Economics Oct 2019To determine the clinical effectiveness and safety of venous thromboembolism (VTE) prophylaxis using US- and Europe-approved anticoagulants relative to...
Effectiveness and safety of betrixaban extended prophylaxis for venous thromboembolism compared with standard-duration prophylaxis intervention in acute medically ill patients: a systematic literature review and network meta-analysis.
To determine the clinical effectiveness and safety of venous thromboembolism (VTE) prophylaxis using US- and Europe-approved anticoagulants relative to extended-duration VTE prophylaxis with betrixaban. Low molecular weight heparins (LMWHs), unfractionated heparin (UFH), fondaparinux sodium and placebo were each compared to betrixaban, as standard-duration VTE prophylaxis for hospitalized, non-surgical patients with acute medical illness at risk of VTE. A systematic literature review was conducted up to June 2019 to identify randomized controlled trials (RCTs) of VTE prophylaxis in hospitalized, non-surgical patients with acute medical illness at risk of VTE. Studies that reported the occurrence of VTE events (including death) and, where possible, major bleeding, from treatment initiation to 20-50 days thereafter were retrieved and extracted. A Bayesian fixed effect network meta-analysis was used to estimate efficacy and safety of betrixaban compared with standard-duration VTE prophylaxis. Seven RCTs were analyzed which compared betrixaban, LMWHs, UFH, fondaparinux sodium, or placebo. There were significantly higher odds (median odds [95% credible interval]) of VTE with LMWHs (1.38 [1.12-1.70]), UFH (1.60 [1.05-2.46]), and placebo (2.37 [1.55-3.66]) compared with betrixaban. There were significantly higher odds of VTE-related death with placebo (7.76 [2.14-34.40]) compared with betrixaban. No significant differences were observed for the odds of major bleeding with all comparators, VTE-related death with any active standard-duration VTE prophylaxis, or of VTE with fondaparinux sodium, compared with betrixaban. In this indirect comparison, betrixaban was shown to be an effective regimen with relative benefits compared with LMWHs and UFH. This indicates that betrixaban could reduce the burden of VTE in at-risk hospitalized patients with acute medical illness who need extended prophylaxis, though without direct comparative evidence, stronger conclusions cannot be drawn.
Topics: Acute Disease; Anticoagulants; Bayes Theorem; Benzamides; Delayed-Action Preparations; Factor Xa Inhibitors; Heparin; Heparin, Low-Molecular-Weight; Humans; Network Meta-Analysis; Patient Safety; Pyridines; Treatment Outcome; Venous Thromboembolism
PubMed: 31314619
DOI: 10.1080/13696998.2019.1645679 -
Clinical Cardiology Jan 2021Although the European Medicines Agency and the US Food and Drug Administration have, respectively, approved rivaroxaban for the prevention of recurrent major adverse... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although the European Medicines Agency and the US Food and Drug Administration have, respectively, approved rivaroxaban for the prevention of recurrent major adverse cardiovascular events in patients with myocardial infarction and stable coronary artery disease, its efficacy and safety is unclear. This meta-analysis aimed to evaluate the benefit and risk of adding rivaroxaban in coronary artery disease (CAD) patients, focusing on treatment effects stratified by different baseline clinical presentations.
HYPOTHESIS
There are differences in treatment effects of adding rivaroxaban among CAD patients with different baseline clinical presentations.
METHODS
Medline, EMBASE, and Cochrane Databases were systematically searched from inception to 21 July 2020 for randomized controlled trials (RCTs) comparing rivaroxaban in CAD patients. The primary efficacy endpoint and safety endpoint were assessed by using Mantel-Haenszel pooled risk ratios (RRs) and 95% confidence intervals (CIs).
RESULTS
Five RCTs that included 43 650 patients were identified. Patients receiving rivaroxaban had a significantly lower risk of the primary efficacy endpoint (RR, 0.86; 95% CI, 0.76-0.97, p = .01) accompanied by increased risk of the primary safety endpoint (RR, 1.83; 95% CI, 1.10-3.05, p = .02). Subgroup analyses showed that in males the risk-benefit appears to be more favorable while in patients ≥65 years, in females, in patients with diabetes, those with mild to moderate impaired renal function, and region of Asia/other seems unfavorable.
CONCLUSION
Rivaroxaban may provide an additional choice for secondary prevention in CAD patients. However, careful estimation of the risk of ischemic and bleeding events using patient characteristics are critical to achieving net benefit.
Topics: Coronary Artery Disease; Factor Xa Inhibitors; Hemorrhage; Humans; Risk Factors; Rivaroxaban
PubMed: 33219708
DOI: 10.1002/clc.23514