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European Journal of Vascular and... Nov 2014The aim was to perform a review of the efficacy and safety of new oral anticoagulants (NOAs) in the management of venous thromboembolism (VTE). (Meta-Analysis)
Meta-Analysis Review
Editor's Choice - efficacy and safety of the new oral anticoagulants dabigatran, rivaroxaban, apixaban, and edoxaban in the treatment and secondary prevention of venous thromboembolism: a systematic review and meta-analysis of phase III trials.
OBJECTIVES
The aim was to perform a review of the efficacy and safety of new oral anticoagulants (NOAs) in the management of venous thromboembolism (VTE).
METHODS
This was a systematic review and meta-analysis. On March 26, 2014, Medline, Embase, and the Cochrane trial register were searched for randomized controlled trials (RCTs) comparing the NOAs dabigatran, rivaroxaban, apixaban, and edoxaban with vitamin K antagonists (VKAs) in VTE treatment and secondary prevention. Two investigators assessed the methodological quality of the RCTs. The main study outcomes (efficacy, safety and net clinical benefit) were expressed as risk ratios (RR) with 95% confidence interval (CI).
RESULTS
Ten RCTs, mostly with low risk of bias, with nearly 38,000 patients, were identified. In six trials of treatment, NOAs were equally effective as VKAs in preventing recurrent symptomatic VTE (RR 0.89, 95% CI 0.75-1.05), but major bleeding occurred less often (1.08% vs. 1.73% for VKAs, RR 0.63, 95% CI 0.51-0.77), leading net clinical benefit to favor NOAs (RR 0.79, 95% CI 0.70-0.90). Fatal bleeding occurred less often with NOAs (0.09% vs. 0.18% for VKAs), a difference that approached statistical significance (RR 0.51, 95% CI 0.26-1.01). In three secondary prevention trials, NOAs reduced VTE recurrence rates to 1.32% (vs. 7.24% with placebo, RR 0.17, 95% CI 0.12-0.24) and fatal pulmonary embolism (PE) (including unexplained deaths) to 0.1% (vs. 0.29% for placebo, RR 0.37, 95% CI 0.10-1.38) at the expense of clinically relevant non-major bleeding (4.3% vs. 1.8% for placebo, RR 2.32, 95% CI 1.65-3.35), but not major bleeding. All-cause mortality rate was reduced to 0.41% with NOAs (vs. 0.86% with placebo, RR 0.38, 95% CI 0.18-0.79). Net clinical benefit favored NOAs (RR 0.21, 95% CI 0.15-0.29), and NNT was 18.
CONCLUSIONS
Compared to VKAs, NOAs are not only effective in treating VTE but also safer in terms of bleeding, thereby conferring clinical benefit. Their safety and efficacy was confirmed further in secondary prevention trials.
Topics: Administration, Oral; Anticoagulants; Benzimidazoles; Clinical Trials, Phase III as Topic; Dabigatran; Humans; Morpholines; Pyrazoles; Pyridines; Pyridones; Rivaroxaban; Secondary Prevention; Thiazoles; Thiophenes; Venous Thromboembolism; beta-Alanine
PubMed: 24951377
DOI: 10.1016/j.ejvs.2014.05.001 -
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 -
Journal of Clinical Medicine Jul 2023Valvular heart disease is a common disease often necessitating valve replacement. Mechanical heart valves (MHVs) are often used in younger patients because of their... (Review)
Review
UNLABELLED
Valvular heart disease is a common disease often necessitating valve replacement. Mechanical heart valves (MHVs) are often used in younger patients because of their longer durability. Their main disadvantage is the need for lifelong anticoagulation. Warfarin is considered a standard treatment, but it is far from perfect. Direct oral anticoagulants (DOACs) are a new and more patient-friendly alternative to warfarin when anticoagulation is required, but have not yet been approved for the indication of mechanical valves.
EVIDENCE ACQUISITION
A literature search of Pubmed, Embase, Web of Science (Core Collection), and Cochrane Library (from inception to May 2023) was performed using a search string that was well defined and not modified during the study. An extensive overview of the search terms used in each database can be found in the Appendix. Only prospective clinical trials were included in this review. A total of 10 publications were included in this review.
RELEVANCE TO CLINICAL PRACTICE
This systematic review summarizes the different types of DOACs and their possible use in the anticoagulation of mechanical valves. We aim to propose future directions in anticoagulation research for mechanical valves.
CONCLUSIONS
DOAC use in MHVs has been halted due to the failure of both dabigatran and apixaban in two major clinical trials. However, rivaroxaban was successful in two small clinical trials. Ample research is still needed to explore new valve designs as well as new anticoagulation targets.
PubMed: 37568386
DOI: 10.3390/jcm12154984 -
Vascular and Endovascular Surgery Oct 2021We performed a systematic review and meta-analysis to evaluate the efficacy and safety of rivaroxaban in patients with PAD for the first time. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We performed a systematic review and meta-analysis to evaluate the efficacy and safety of rivaroxaban in patients with PAD for the first time.
METHODS
We searched MEDLINE, EMBASE and the Cochrane Library database for randomized controlled trials (RCTs) conducted for PAD.
RESULTS
Three trials which contained 14873 patients were included for final meta-analysis. The results showed patients with rivaroxaban was associated with reduction in primary efficacy outcome (RR 0.83; 95% CI 0.76 to 0.90; p < 0.001). The RR was 0.85 (0.71 to 1.01) for patients with rivaroxaban alone and 0.81 (0.74 to 0.89) for those with rivaroxaban plus aspirin (p for heterogeneity between groups = 0.65). Patients with rivaroxaban showed a lower rate of acute limb ischemia (0.56; 0.47 to 0.66; p < 0.001). There was a trend toward a reduction in the rate of major amputation for vascular causes in the rivaroxaban arm (0.81; 0.63 to 1.03; p = 0.08). Compared with control, rivaroxaban therapy did not reduce the risks of myocardial infarction (0.87, 0.73 to 1.04, p = 0.12), ischemic stroke (0.85, CI 0.68 to 1.06, p = 0.15), death from cardiovascular causes (0.99, 0.85 to 1.15, p = 0.91) or death from any cause (1.00, 0.90 to 1.12, p = 0.98). Rivaroxaban therapy was associated with a 1.57-fold higher major bleeding rate as compared with those with aspirin or warfarin alone.
CONCLUSIONS
Overall, the risks of the primary efficacy outcomes or adverse limb events were significantly lower with rivaroxaban than with aspirin or warfarin alone in patients with PAD. It also points out the significant major bleeding that occur because of such therapies.
Topics: Aged; Amputation, Surgical; Disease Progression; Factor Xa Inhibitors; Female; Hemorrhage; Humans; Limb Salvage; Male; Peripheral Arterial Disease; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Rivaroxaban; Time Factors; Treatment Outcome
PubMed: 34032469
DOI: 10.1177/15385744211012916 -
American Journal of Cardiovascular... Jan 2021This meta-analysis was conducted to compare the efficacy and safety of rivaroxaban with warfarin in patients with atrial fibrillation (AF) and diabetes mellitus. (Meta-Analysis)
Meta-Analysis
AIMS
This meta-analysis was conducted to compare the efficacy and safety of rivaroxaban with warfarin in patients with atrial fibrillation (AF) and diabetes mellitus.
METHODS
PubMed, Embase, Cochrane Library, and Web of Science databases were systematically searched from the establishment of databases up to 15 October 2019. Studies on efficacy and safety outcomes of rivaroxaban and warfarin were included. Efficacy and safety outcomes, including stroke, ischemic stroke, stroke or systemic embolism, myocardial infarction, major adverse cardiac events, major bleeding, intracranial hemorrhage, and major gastrointestinal bleeding were collected for meta-analysis.
RESULTS
Compared with warfarin, rivaroxaban could significantly reduce stroke (risk ratio [RR] 0.77; 95% confidence interval [CI] 0.63-0.95; P = 0.01), ischemic stroke (RR 0.74; 95% CI 0.63-0.87; P = 0.0004), stroke or systemic embolism (RR 0.73; 95% CI 0.60-0.89; P = 0.002), myocardial infarction (RR 0.68; 95% CI 0.56-0.82; P < 0.0001), and major adverse cardiac events (RR 0.71; 95% CI 0.53-0.94; P = 0.02) in patients with AF and diabetes. Moreover, rivaroxaban was associated with a lower risk of major bleeding (RR 0.79; 95% CI 0.65-0.96; P = 0.02), intracranial hemorrhage (RR 0.52; 95% CI 0.39-0.69; P < 0.00001), and major gastrointestinal bleeding (RR 0.74; 95% CI 0.56-0.98; P = 0.04). Similar results were obtained in stratified meta-analysis of cohort studies.
CONCLUSION
Our study suggests a favorable risk-benefit profile of rivaroxaban, with superior efficacy and safety over warfarin in patients with AF and diabetes.
Topics: Anticoagulants; Atrial Fibrillation; Clinical Trials as Topic; Diabetes Mellitus; Hemorrhage; Humans; Myocardial Infarction; Rivaroxaban; Stroke; Warfarin
PubMed: 32514866
DOI: 10.1007/s40256-020-00407-z -
The Bone & Joint Journal Aug 2016There is uncertainty regarding the optimal means of thromboprophylaxis following total hip and knee arthroplasty (THA, TKA). This systematic review presents the evidence... (Meta-Analysis)
Meta-Analysis Review
AIMS
There is uncertainty regarding the optimal means of thromboprophylaxis following total hip and knee arthroplasty (THA, TKA). This systematic review presents the evidence for acetylsalicylic acid (aspirin) as a thromboprophylactic agent in THA and TKA and compares it with other chemoprophylactic agents.
MATERIALS AND METHODS
A search of literature published between 2004 and 2014 was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 13 studies were eligible for inclusion.
RESULTS
Evidence from one good quality randomised controlled trial (RCT) showed no difference in rates of venous thrombo-embolism (VTE) in patients given aspirin or low molecular weight heparin (LMWH) following TKA. There was insufficient evidence from trials with moderate to severe risk of bias being present to suggest aspirin is more or less effective than LMWH, warfarin or dabigatran for the prevention of VTE in TKA or THA. Compared with aspirin, rates of asymptomatic deep vein thrombosis (DVT) in TKA may be reduced with rivaroxaban but insufficient evidence exists to demonstrate an effect on incidence of symptomatic DVT. Compared with aspirin there is evidence of more wound complications following THA and TKA with dabigatran and in TKA with rivaroxaban. Some studies highlighted concerns over bleeding complications and efficacy of aspirin.
CONCLUSION
The results suggest aspirin may be considered a suitable alternative to other thromboprophylactic agents following THA and TKA. Further investigation is required to fully evaluate the safety and efficacy of aspirin. Cite this article: Bone Joint J 2016;98-B:1056-61.
Topics: Anticoagulants; Arthroplasty, Replacement, Hip; Arthroplasty, Replacement, Knee; Aspirin; Clinical Protocols; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Humans; Intraoperative Care; Randomized Controlled Trials as Topic; Registries; Venous Thromboembolism; Warfarin
PubMed: 27482017
DOI: 10.1302/0301-620X.98B8.36957 -
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 -
Journal of Clinical Medicine Jun 2022There is a plethora of real-world data on the safety and effectiveness of direct-acting oral anticoagulants (DOACs); however, study heterogeneity has contributed to... (Review)
Review
BACKGROUND
There is a plethora of real-world data on the safety and effectiveness of direct-acting oral anticoagulants (DOACs); however, study heterogeneity has contributed to inconsistent findings. We compared the effectiveness and safety of apixaban with those of other direct-acting oral anticoagulants (DOACs) and vitamin K antagonists (VKA e.g., warfarin).
METHODS
A systematic review and meta-analysis was conducted retrieving data from PubMed, SCOPUS and Web of Science from January 2009 to December 2021. Studies that evaluated apixaban (intervention) prescribed for adults (aged 18 years or older) with AF for stroke prevention compared to other DOACs or VKAs were identified. Primary outcomes included stroke/systemic embolism (SE), all-cause mortality, and major bleeding. Secondary outcomes were intracranial haemorrhage (ICH) and ischaemic stroke. Randomised controlled trials and non-randomised trials were considered for inclusion.
RESULTS
In total, 67 studies were included, and 38 studies were meta-analysed. Participants taking apixaban had significantly lower stroke/SE compared to patients taking VKAs (relative risk (RR) 0.77, 95% confidence interval (CI) 0.64-0.93, I = 94%) and dabigatran (RR 0.84, 95% CI 0.74-0.95, I = 66%), but not to patients administered rivaroxaban. There was no statistical difference in mortality between apixaban and VKAs or apixaban and dabigatran. Compared to patients administered rivaroxaban, participants taking apixaban had lower mortality rates (RR 0.83, 95% CI 0.71-0.96, I = 96%). Apixaban was associated with a significantly lower risk of major bleeding compared to VKAs (RR 0.58, 95% CI 0.52-0.65, I = 90%), dabigatran (RR 0.79, 95% CI 0.70-0.88, I = 78%) and rivaroxaban (RR 0.61, 95% CI 0.53-0.70, I = 87%).
CONCLUSIONS
Apixaban was associated with a better overall safety and effectiveness profile compared to VKAs and other DOACs.
PubMed: 35807073
DOI: 10.3390/jcm11133788 -
Cardiovascular Revascularization... Sep 2021The use of warfarin in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) has been implicated with efficacy and safety concerns. Evidence on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The use of warfarin in patients with atrial fibrillation (AF) and end-stage renal disease (ESRD) has been implicated with efficacy and safety concerns. Evidence on the role of direct oral anticoagulants (DOACs) in this population is limited.
METHODS
Electronic databases were searched and articles comparing the safety and efficacy of warfarin with apixaban or rivaroxaban were identified. Pooled hazard ratios (HR) were computed using a random-effects model.
RESULTS
A total of eight articles consisting of 30,806 patients; (rivaroxaban 2196, apixaban 2745 and warfarin 25,865) were identified. The pooled HR for major bleeding events favored apixaban over warfarin (0.53, 95% confidence interval (CI) 0.33-0.84, p = 0.008). Apixaban was similar to warfarin in terms of clinically relevant non-major bleeding (HR 1.08, 95% CI 0.64-1.84, p = 0.77) and stroke events (HR 1.09, 95% CI 0.85, 1.39, p = 0.99). There was no significant difference in the risk of major bleeding events (HR 0.95, 95% CI 0.50-1.81, p = 0.88) and stroke between rivaroxaban (HR 1.39, 95% CI, 0.59-3.29, p = 0.09) and warfarin. The combined results of major bleeding in the apixaban group were not affected by the sensitivity analysis.
CONCLUSIONS
Apixaban may have a lower risk of major bleeding and comparable risk of stroke when compared with warfarin in AF patients with ESRD.
Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Humans; Kidney Failure, Chronic; Pyrazoles; Pyridones; Rivaroxaban; Stroke; Warfarin
PubMed: 34420589
DOI: 10.1016/j.carrev.2020.09.041 -
Clinical and Applied... 2020There is no direct evidence comparing the 2 most commonly prescribed direct oral anticoagulants, apixaban and rivaroxaban, used for stroke prevention in nonvalvular... (Comparative Study)
Comparative Study
There is no direct evidence comparing the 2 most commonly prescribed direct oral anticoagulants, apixaban and rivaroxaban, used for stroke prevention in nonvalvular atrial fibrillation (NVAF). A number of network meta-analyses (NMAs) of randomized control trials and real-world evidence (RWE) studies comparing the efficacy, effectiveness, and safety of apixaban and rivaroxaban have been published; however, a comprehensive evidence review across the available body of evidence is lacking. In this study, we aimed to systematically review and evaluate the clinical outcomes of apixaban and rivaroxaban using a combination of data gleaned from both NMAs and RWE studies. The review identified 21 NMAs and 5 RWE studies. The data demonstrated that apixaban was associated with fewer major bleeding events compared to rivaroxaban. There was no difference in the efficacy/effectiveness profiles between these treatments. Bleeding is a serious complication of anticoagulation therapy for the management of NVAF, and is associated with increased rates of hospitalization, morbidity, mortality, and health-care expenditure. The majority of studies in this comprehensive evidence review suggests that apixaban has a lower risk of major bleeding events compared to rivaroxaban in patients with NVAF.
Topics: Aged; Atrial Fibrillation; Female; Hemorrhage; Humans; Male; Middle Aged; Network Meta-Analysis; Pyrazoles; Pyridones; Rivaroxaban
PubMed: 31918558
DOI: 10.1177/1076029619898764