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Frontiers in Pharmacology 2023A lack of clarity persists regarding the efficacy and risks associated with direct oral anticoagulants (DOACs) in end-stage renal disease (ESRD) patients with atrial...
A lack of clarity persists regarding the efficacy and risks associated with direct oral anticoagulants (DOACs) in end-stage renal disease (ESRD) patients with atrial fibrillation (AF) undergoing dialysis, primarily due to limited retrospective studies. Therefore, the objective of this study was to evaluate the existing data and propose a practical protocol for the clinical utilization of DOACs in ESRD patients with AF undergoing dialysis. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for clinical studies evaluating DOACs in ESRD patients with AF on dialysis published up to 2 February 2023. DOACs included warfarin, dabigatran, apixaban, edoxaban, and rivaroxaban. The outcomes were mortality, ischemic stroke, hemorrhagic stroke, any stroke, gastrointestinal bleeding, major bleeding, intracranial bleeding, and minor bleeding. Compared with placebo, apixaban (HR = 0.97, 95% CI: 0.88-1.07), rivaroxaban (HR = 0.91, 95% CI: 0.76-1.10), and warfarin (HR = 0.96, 95% CI: 0.90-1.01) did not reduce mortality. Regarding direct comparisons of mortality, the comparisons of warfarin vs. apixaban (HR = 0.99, 95% CI: 0.92-1.06), placebo vs. warfarin (HR = 1.04, 95% CI: 0.99-1.11), and rivaroxaban vs. warfarin (HR = 0.96, 95% CI: 0.80-1.14) did not significantly reduce mortality. Based on the surface under the cumulative ranking curve, rivaroxaban (75.53%), warfarin (62.14%), and apixaban (45.6%) were the most effective interventions for managing mortality, and placebo (16.74%) was the worst. In conclusion, rivaroxaban demonstrated efficacy in reducing mortality and the incidence of ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage. Dabigatran is recommended for the prevention of hemorrhagic stroke. However, caution should be exercised due to the risk of major bleeding. Warfarin can effectively reduce minor bleeding but does not offer significant protection against gastrointestinal or intracranial bleeding. Apixaban was not recommended for mortality reduction or for preventing ischemic or hemorrhagic strokes. Further research will be necessary to establish specific clinical protocols.
PubMed: 38161701
DOI: 10.3389/fphar.2023.1320939 -
Journal of Clinical Medicine Jul 2022Venous thromboembolism (VTE) is a serious complication that can occur during and after postoperative treatment, including in treatment after orthopedic surgery. The... (Review)
Review
Venous thromboembolism (VTE) is a serious complication that can occur during and after postoperative treatment, including in treatment after orthopedic surgery. The current guidelines for VTE prophylaxis in postoperative patients recommend the use of LMWHs, one of which is enoxaparin. Another recommendation for use in pharmacological VTE prophylaxis is rivaroxaban, which has better efficacy than enoxaparin but a higher bleeding risk. The aim of this systematic review is to provide an update on the profile of rivaroxaban for VTE prophylaxis after orthopedic surgery. PubMed, SCOPUS, EMBASE, and EBSCOhost were searched up until May 2022. The outcome sought was efficacy and safety, described by the incidence of VTE and incidence of bleeding, respectively. Five randomized controlled trials (RCT) were finally included. Rivaroxaban was confirmed to have better efficacy by significantly reducing the risk of VTE and all-cause mortality (RR = 0.38; 95% CI = 0.27-0.54) compared to enoxaparin. However, regarding the safety variable, no significant difference was found between the incidence of major bleeding in rivaroxaban and enoxaparin (RR = 0.97; 95% CI = 0.56-1.68). The results of the analysis show that rivaroxaban has better efficacy than enoxaparin but the same safety profile, so when used, the bleeding of patients should still be monitored.
PubMed: 35887834
DOI: 10.3390/jcm11144070 -
Journal of Vascular Surgery. Venous and... Nov 2021Direct oral anticoagulants (DOACs) have been recommended for the treatment of deep vein thrombosis (DVT). However, the benefits are uncertain for the prevention of... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Direct oral anticoagulants (DOACs) have been recommended for the treatment of deep vein thrombosis (DVT). However, the benefits are uncertain for the prevention of post-thrombotic syndrome (PTS). We performed a systematic review and meta-analysis of reported studies to assess the efficacy of DOACs vs vitamin K antagonists for the risk reduction of PTS in patients with DVT.
METHODS
We searched PubMed, Medline, the Cochrane Library, Embase, and the Web of Science for studies reporting on the development of PTS after acute DVT. The outcomes were the risk reduction of PTS, PTS severity, the presence of residual vein thrombosis, and the incidence of recurrent venous thromboembolic (VTE) events.
RESULTS
A total of 59,199 patients from six retrospective and two randomized controlled studies had received DOAC treatment and were followed up for the development of PTS. In all studies, rivaroxaban had been compared with initial low-molecular-weight heparin followed by warfarin. Of the 59,199 patients, 19,840 (33.5%) had received rivaroxaban and 39,377 (66.5%), warfarin. The rivaroxaban group had a significant reduction in PTS development compared with the warfarin group (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.43-0.63; P < .001). Severe PTS was less common in the rivaroxaban group than in the warfarin group (3.7% vs 6.4%; OR, 0.55; 95% CI, 0.36-0.85; P = .024). Additionally, rivaroxaban was associated with a significant reduction in VTE recurrence (OR, 0.83; 95% CI, 0.59-1.18; P = .03) and low rates of residual vein thrombosis compared with warfarin (36.5% vs 51.8%; P = .037).
CONCLUSIONS
Rivaroxaban after acute DVT was associated with a reduced risk of PTS compared with warfarin. Patients treated with rivaroxaban more rarely developed severe PTS and recurrent VTE events compared with patients treated with warfarin.
Topics: Factor Xa Inhibitors; Humans; Postthrombotic Syndrome; Rivaroxaban; Treatment Outcome
PubMed: 33965611
DOI: 10.1016/j.jvsv.2021.04.016 -
Europace : European Pacing,... Oct 2023Limited real-world data show that rivaroxaban following dosage criteria from either ROCKET AF [20 mg/day or 15 mg/day if creatinine clearance (CrCl) < 50 mL/min]... (Meta-Analysis)
Meta-Analysis
Comparisons of effectiveness and safety between on-label dosing, off-label underdosing, and off-label overdosing in Asian and non-Asian atrial fibrillation patients treated with rivaroxaban: a systematic review and meta-analysis of observational studies.
AIMS
Limited real-world data show that rivaroxaban following dosage criteria from either ROCKET AF [20 mg/day or 15 mg/day if creatinine clearance (CrCl) < 50 mL/min] or J-ROCKET AF (15 mg/day or 10 mg/day if CrCl < 50 mL/min) is associated with comparable risks of thromboembolism and bleeding with each other in patients with non-valvular atrial fibrillation (NVAF). We are aimed to study whether these observations differ between Asian and non-Asian subjects.
METHODS AND RESULTS
A systematic review and meta-analysis with random effects was conducted to estimate the aggregate hazard ratio (HR) and 95% confidence interval (CI) using PubMed and MEDLINE databases from 8 September 2011 to 31 December 2022 searched for adjusted observational studies that reported relevant clinical outcomes of NVAF patients receiving rivaroxaban 10 mg/day if CrCl > 50 mL/min, on-label dose rivaroxaban eligible for ROCKET AF or J-ROCKET AF, and rivaroxaban 20 mg/day if CrCl < 50 mL/min. Effectiveness and safety endpoints were compared between ROCKET AF and J-ROCKET AF dosing regimen in Asian and non-Asian subjects, separately. Also, risks of events of rivaroxaban 10 mg/day despite of CrCl > 50 mL/min and rivaroxaban 20 mg/day despite of CrCl < 50 mL/min were compared to that of 'ROCKET AF/J-ROCKET AF dosing'. Sensitivity analyses were performed by sequential elimination of each study from the pool. The meta-regression analysis was performed to explore the influence of potential factors on the effectiveness and safety outcomes. Eighteen studies involving 67 571 Asian and 54 882 non-Asian patients were included. Rivaroxaban following J-ROCKET AF criteria was associated with comparable risks of thromboembolism in the Asian subgroup, whereas rivaroxaban following J-ROCKET AF criteria was associated with higher risks of all-cause mortality (HR:1.30; 95% CI:1.05-1.60) compared with that of ROCKET AF criteria in the non-Asian population. There were no differences in risks of major bleeding between rivaroxaban following J-ROCKET AF vs. ROCKET AF criteria either in the Asian or non-Asian population. The use of rivaroxaban 10 mg despite of CrCl > 50 mL/min was associated with a higher risk of thromboembolism (HR:1.64; 95% CI:1.28-2.11) but lower risk of major bleeding (HR:0.72; 95% CI:0.57-0.90) compared with eligible dosage criteria. The use of rivaroxaban 20 mg despite of CrCl < 50 mL/min was associated with worse clinical outcomes in the risks of thromboembolism (HR:1.32; 95% CI:1.09-1.59), mortality (HR:1.33; 95% CI:1.10-1.59), and major bleeding (HR:1.26; 95% CI:1.03-1.53) compared with eligible dosage criteria. The pooled results were generally in line with the primary effectiveness and safety outcomes by removing a single study at one time. Meta-regression analyses failed to detect the bias in most potential patient characteristics associated with the clinical outcomes.
CONCLUSION
Rivaroxaban dosing regimen following J-ROCKET criteria may serve as an alternative to ROCKET AF criteria for the Asian population with NVAF, whereas the dosing regimen following ROCKET AF criteria was more favourable for the non-Asian population. The use of rivaroxaban 10 mg despite of CrCl > 50 mL/min was associated with a higher risk of thromboembolism but a lower risk of major bleeding, while use of rivaroxaban 20 mg despite of CrCl < 50 mL/min was associated with worse outcome in most clinical events.
Topics: Humans; Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Hemorrhage; Off-Label Use; Rivaroxaban; Stroke; Thromboembolism; Treatment Outcome; Warfarin; Observational Studies as Topic
PubMed: 37738425
DOI: 10.1093/europace/euad288 -
Journal of Clinical Pharmacy and... Feb 2011Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative... (Comparative Study)
Comparative Study Meta-Analysis Review
WHAT IS KNOWN AND OBJECTIVE
Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta-analysis, and adjusted indirect comparison.
METHODS
We searched PubMed, EMBASE, trial registries and regulatory documents through May 2009 for randomized controlled trials (RCTs) of dabigatran (150 and 220 mg daily) and rivaroxaban (10 mg daily) compared with enoxaparin (40-60 mg daily) in elective orthopaedic surgery. We used random effects meta-analysis to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI) for the outcomes of total venous thromboembolism, VTE (deep venous thrombosis, non-fatal pulmonary embolism and all-cause mortality), and haemorrhagic adverse events (major and clinically relevant non-major bleeds). Adjusted indirect comparison was used for the pooled RRs of dabigatran and rivaroxaban with enoxaparin as the common control.
RESULTS
Rivaroxaban was superior to enoxaparin for the prevention of venous thromoboembolism (RR 0.56, 95% CI 0.43-0.73, P<0.0001), with a trend for increased haemorrhage (RR 1.26, 95% CI 0.94-1.69, P=0.13). Dabigatran was not superior to enoxaparin for prevention of VTE (RR 1.12, 95% 0.97-1.29, P=0.12), and did not reduce haemorrhage risk (RR 1.10, 95% 0.90-1.35, P=0.32). Adjusted indirect comparison showed that rivaroxaban was superior to dabigatran in preventing VTE, RR 0.50 (95% CI 0.37-0.68), but with a slight trend towards increased haemorrhage RR 1.14 (95% CI 0.80-1.64).
WHAT IS NEW AND CONCLUSION
Rivaroxaban may be more effective than dabigatran for prevention of VTE after elective orthopaedic surgery but might also slightly increase the risk of haemorrhage.
Topics: Anticoagulants; Antithrombins; Benzimidazoles; Dabigatran; Enoxaparin; Factor Xa Inhibitors; Hemorrhage; Humans; Morpholines; Orthopedic Procedures; Postoperative Complications; Pulmonary Embolism; Rivaroxaban; Thiophenes; Venous Thromboembolism; Venous Thrombosis; beta-Alanine
PubMed: 21198726
DOI: 10.1111/j.1365-2710.2010.01162.x -
Pharmacotherapy Jun 2018While not designated as guideline-recommended first-line anticoagulation therapy, about one in five patients in the United States receive rivaroxaban for the treatment... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
While not designated as guideline-recommended first-line anticoagulation therapy, about one in five patients in the United States receive rivaroxaban for the treatment of cancer-associated venous thrombosis (CAT).
METHODS
A systematic review and meta-analysis were performed to evaluate the incidences of recurrent venous thromboembolism (VTE), major bleeding, and all-cause mortality in rivaroxaban patients treated for CAT in routine practice. Literature searches of MEDLINE and SCOPUS were performed through September 2017 to identify real-world studies of ≥ 20 patients evaluating the incidence of recurrent VTE, major bleeding, or all-cause mortality in CAT patients anticoagulated with rivaroxaban. Using a Hartung-Knapp random-effects model, the pooled incidence estimates and 95% confidence intervals (CIs) were calculated for each end point.
RESULTS
Six studies evaluating rivaroxaban for CAT were identified. Of these, three were prospective and three were retrospective. Study sample sizes ranged from 41 to 949 patients, and duration of follow-up ranged from 164 to 496 days. The most frequent active cancer sites reported in studies were gastrointestinal (range: 12.0-56.0%), genitourinary (range: 8.6-26.0%), and breast (range: 9.3-25.5%). The weighted average incidences of recurrent VTE, major bleeding, and all-cause mortality were 4.2% (95% CI = 2.6-6.6%; I = 31%), 2.9% (95% CI = 1.6-5.0%; I = 59%), and 16.1% (95% CI = 6.0-36.6%; I = 96%).
CONCLUSIONS
This meta-analysis suggests that incidences of recurrent VTE and major bleeding among rivaroxaban-managed patients are not dissimilar to those seen in recent randomized trials of anticoagulation in CAT. The pooled incidence for mortality was lower than reported in many anticoagulation CAT trials. This may suggest that rivaroxaban is being used in CAT patients who have less severe cancer.
Topics: Factor Xa Inhibitors; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism
PubMed: 29604102
DOI: 10.1002/phar.2113 -
Pharmaceutics Feb 2023Rivaroxaban has been widely used to prevent and treat various thromboembolic diseases for more than a decade. However, whether a lower dose of rivaroxaban is required... (Review)
Review
Rivaroxaban has been widely used to prevent and treat various thromboembolic diseases for more than a decade. However, whether a lower dose of rivaroxaban is required for Asians is still debatable. This review aimed to explore the potential ethnic difference in pharmacokinetic/pharmacodynamic (PK/PD) characteristics between Asians and Caucasians. A systematic search was conducted and twenty-four studies were identified, of which 10 were conducted on Asian adults, 11 on predominantly Caucasian adults, and 3 on Caucasian pediatrics. The apparent clearance (CL/F) of rivaroxaban in Caucasian adults with non-valvular atrial fibrillation (6.45-7.64 L/h) was about 31-43% higher than that in Asians (4.46-5.98 L/h) taking 10~20 mg rivaroxaban every 24 h. Moreover, there was no obvious difference in CL/F among Japanese, Chinese, Thai, and Irani people. Regarding PK/PD relationship, prothrombin time was linked to rivaroxaban concentration in a linear or near-linear manner, and Factor Xa activity was linked with the E model. The exposure-response relationship was comparable between Asians and Caucasians. Renal function has a significant influence on CL/F, and no covariate was recognized for exposure-response relationship. In conclusion, a lower dose of rivaroxaban might be required for Asians, and further studies are warranted to verify this ethnic difference to facilitate optimal dosing regimens.
PubMed: 36839909
DOI: 10.3390/pharmaceutics15020588 -
Clinical Pharmacokinetics Dec 2022Venous thromboembolism (VTE) is a leading cause of morbidity and mortality globally. The direct oral anticoagulants, including rivaroxaban, are relatively novel...
INTRODUCTION
Venous thromboembolism (VTE) is a leading cause of morbidity and mortality globally. The direct oral anticoagulants, including rivaroxaban, are relatively novel therapeutic options in the treatment and prevention of VTE. There is a conflicting and inconclusive evidence surrounding the pharmacokinetics (PK) of rivaroxaban in patients with VTE who are obese.
OBJECTIVES
We conducted a systematic review to provide an overview, and to synthesize the available evidence in the current literature pertaining to rivaroxaban PK in obese subjects who are healthy or diseased.
METHODS
The PubMed, Embase, ScienceDirect, Rayyan, and Cochrane Library databases were systematically searched from 1 May 2021 through 28 February 2022. Studies investigating rivaroxaban PK in adult obese subjects were included in the review. Pertinent data, including anthropometric parameters, rivaroxaban dosage regimen, PK parameters, PK model, and outcome measures were extracted. Reference values of rivaroxaban PK parameters in the general population were used for comparison purposes. The review protocol was registered in the PROSPERO database (CRD42020177770).
RESULTS
In the 11 studies included in this systematic review, over 7140 healthy or diseased subjects received rivaroxaban therapy, with varying clinical indications in the diseased population. The reported PK parameters of rivaroxaban in obese subjects compared with reference values in the general population were variable. The reported values of the volume of distribution (V) among obese subjects (73.4-82.8 L) fell within the range of values reported/calculated for the general population (59.4-104 L), assuming complete bioavailability. However, some of the reported values of clearance (CL) in obese subjects (7.86-16.8 L.h) do not fall within the range of values reported/calculated for the general population (5.57-11.3 L.h). The reported maximum plasma concentrations in obese subjects versus the general population following a 10 mg dose were 149 vs. 143-180 µg.L, and following a 20 mg dose were 214-305 vs. 299-360 µg.L, respectively. The area under the plasma concentration versus time curves (AUC) over different intervals in obese subjects versus the general population following a 10 mg dose were 1155 (AUC from time zero to infinity [AUC]) vs. 1029 (AUC) µg.h.L; and 1204-2800 (AUC from time zero to 24 h [AUC]) vs. 3200 (AUC) µg.h.L, respectively, following a 20 mg dose. The reported values of half-life and time to reach the maximum plasma concentration in obese subjects versus the general population were not consistent across studies.
CONCLUSION
Variable changes and inconsistencies in different rivaroxaban PK parameters were reported in obese subjects. Further well-designed studies are warranted to better characterize the PK and clinical outcomes of rivaroxaban in subjects with obesity.
Topics: Adult; Humans; Rivaroxaban; Venous Thromboembolism; Half-Life; Obesity; Biological Availability; Anticoagulants
PubMed: 36201149
DOI: 10.1007/s40262-022-01160-z -
Supportive Care in Cancer : Official... Dec 2022The efficacy and safety of direct oral anticoagulants (DOACs), including dabigatran, apixaban, rivaroxaban, and edoxaban, for preventing and treating venous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The efficacy and safety of direct oral anticoagulants (DOACs), including dabigatran, apixaban, rivaroxaban, and edoxaban, for preventing and treating venous thromboembolism (VTE) in patients with cancer is unclear.
METHODS
We searched the PubMed, Embase, Web of Science, and Cochrane Library databases from the establishment to November 30, 2021. In the frequency-based network meta-analysis, the odds ratio with a 95% confidence interval was reported. The relative ranking probability of each group was generated based on the surface under the cumulative ranking curve (SUCRA).
RESULTS
We included 15 randomized controlled trials involving a total of 6162 patients. Apixaban reduced the risk of VTE compared with low-molecular heparin [OR = 0.53, 95% CI (0.32, 0.89)]. The efficacy of drugs was ranked from highest to lowest as follows: apixaban (SUCRA, 81.0), rivaroxaban (73.0), edoxaban (65.9), dabigatran (51.4), warfarin (30.8), and low-molecular-weight heparin (LMWH) (27.4). Edoxaban increased the risk of major bleeding compared with LMWH [OR = 1.83, 95% CI (1.04, 3.22)]. The safety of drugs was ranked from highest to lowest as follows: major bleeding-apixaban (SUCRA, 68.5), LMWH (55.1), rivaroxaban (53.0), warfarin (35.9), dabigatran (29.2), edoxaban (16.5) and clinically relevant non-major bleeding-LMWH (73.0), apixaban (57.8), edoxaban (45.8), rivaroxaban (35.3), and warfarin (10.8).
CONCLUSIONS
For preventing and treating VTE, in terms of VTE occurrence and major bleeding, apixaban had the lowest risk; in terms of clinically relevant non-major bleeding, LMWH had the lowest risk, followed by apixaban. Generally, apixaban is the most efficient and safest DOAC and presents better efficacy and relatively low bleeding risk among the VTE prevention and treatment drugs for patients with cancer.
Topics: Humans; Venous Thromboembolism; Dabigatran; Rivaroxaban; Warfarin; Heparin, Low-Molecular-Weight; Network Meta-Analysis; Administration, Oral; Anticoagulants; Hemorrhage; Neoplasms
PubMed: 36318341
DOI: 10.1007/s00520-022-07433-4 -
Blood Advances Aug 2019Both apixaban and rivaroxaban have been approved for use in acute venous thromboembolism (VTE). Although indirect comparison through network meta-analyses of randomized... (Meta-Analysis)
Meta-Analysis
Both apixaban and rivaroxaban have been approved for use in acute venous thromboembolism (VTE). Although indirect comparison through network meta-analyses of randomized trials have been performed to compare the efficacy and safety of these agents, further comparison between these agents was lacking until recently. We sought to systematically review and carry out a meta-analysis of studies to further compare apixaban with rivaroxaban from multiple studies done in the real-world settings. Studies comparing rivaroxaban with apixaban in patients with acute VTE were identified through electronic literature searches of MEDLINE, EMBASE, Scopus, and the Cochrane library up to May 2019. Study-specific risk ratios (RRs) were calculated and combined using a random-effects model meta-analysis. In an analysis involving 24 041 patients, recurrent VTE within 6 months occurred in 56 of 4897 patients (1.14%) in the apixaban group and 258 of 19 144 patients (1.35%) in the rivaroxaban group (RR, 0.89; 95% confidence interval [CI], 0.67-1.19; = .45). Clinically relevant major bleeding occurred in 85 of 11 559 patients (0.74%) in the apixaban group and 350 of 33 909 patients (1.03%) in the rivaroxaban group (RR, 0.73; 95% CI, 0.58-0.93; = .01). Clinically relevant nonmajor bleeding occurred in 169 of 3417 patients (4.95%) in the apixaban group and 1094 of 12 475 patients (8.77%) in the rivaroxaban group (RR, 0.59; 95% CI, 0.50-0.70; < .01). Apixaban shows equivalent efficacy in prevention of recurrent VTE but decreased risk of major and minor bleeding events compared with rivaroxaban.
Topics: Blood Coagulation; Hemorrhage; Humans; Odds Ratio; Pyrazoles; Pyridones; Rivaroxaban; Treatment Outcome; Venous Thromboembolism
PubMed: 31405948
DOI: 10.1182/bloodadvances.2019000572