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Journal of Managed Care & Specialty... Jun 2020Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM),... (Review)
Review
Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Pearson is employed by ICER; Synnott was employed by ICER at the time of this report. Ollendorf, Campbell, and McQueen received grants from ICER for work on this review. Ollendorf also reports advisory board, consulting, and other fees from Sarepta Therapeutics, DBV Technologies, EMD Serono, Gerson Lehman Group, The CEA Registry Sponsors, Autolus, Analysis Group, Amgen, AbbVie, Cytokinetics, Aspen Institute/University of Southern California, and University of Colorado, unrelated to this review.
Topics: Aspirin; Cardiovascular Diseases; Cost-Benefit Analysis; Dose-Response Relationship, Drug; Drug Costs; Drug Therapy, Combination; Eicosapentaenoic Acid; Hemorrhage; Humans; Models, Economic; Randomized Controlled Trials as Topic; Rivaroxaban; Time Factors; Treatment Outcome
PubMed: 32463783
DOI: 10.18553/jmcp.2020.26.6.782 -
BMC Neurology Feb 2021New Oral Anticoagulants (NOACs) such as Rivaroxaban are introduced as alternatives to conventional vitamin-K antagonists in the long-term treatment of thrombotic events...
BACKGROUND
New Oral Anticoagulants (NOACs) such as Rivaroxaban are introduced as alternatives to conventional vitamin-K antagonists in the long-term treatment of thrombotic events due to their lower bleeding risk. There is a lack of evidence on the effectiveness and safety of Rivaroxaban in Cerebral venous thrombosis (CVT). This study aims to assess the effectiveness and bleeding risk of Rivaroxaban in comparison with Warfarin for the treatment of CVT.
MATERIALS AND METHODS
36 patients with diagnosis of CVT were included. Clinical and background information was assessed on admission and patients were followed for at least 12 months. Measured outcomes were modified Rankin Scale (mRS), evidence of recanalization on contrast-enhanced Brain MR venography (MRV) and major or minor bleeding. Patients were divided into two groups according to the type of oral anticoagulant (Rivaroxaban vs Warfarin). Groups were compared in terms of final outcomes and side effects.
RESULT
Overall, 13 (36.11%) patients received Warfarin and 23 (63.89%) received Rivaroxaban. Optimal mRS score (0-1) was attained in 9 of 10 (90%) of patients treated with Rivaroxaban and 19 of 22 (86.36%) of patients received Warfarin. MRV showed complete or partial recanalization in 12 of 14 (85.71%) patients treated with Rivaroxaban and all patients in the Warfarin group. There was no significant difference between the two groups in terms of major and minor hemorrhage.
CONCLUSION
Rivaroxaban holds promise for the treatment of CVT.
Topics: Adult; Anticoagulants; Factor Xa Inhibitors; Female; Humans; Intracranial Thrombosis; Male; Middle Aged; Rivaroxaban; Treatment Outcome; Venous Thrombosis; Warfarin
PubMed: 33588777
DOI: 10.1186/s12883-021-02091-1 -
The American Journal of Medicine Sep 2017The health implications of obesity are myriad and multifaceted. Physiologic changes associated with obesity can affect the absorption, distribution, metabolism, and... (Review)
Review
The health implications of obesity are myriad and multifaceted. Physiologic changes associated with obesity can affect the absorption, distribution, metabolism, and excretion of administered drugs, thereby altering their pharmacologic profiles. In 2016, the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis published recommendations about the use of direct oral anticoagulants (DOACs) in obese patients. This guidance provides uniform recommendations for all DOACs, yet data suggest that individual agents may be affected to different degrees by obesity. Moreover, there are no recommendations currently available to guide DOAC use in bariatric surgery patients, in whom anatomic and physiologic changes to the digestive system can influence drug pharmacokinetics. Our review of the available literature indicates that the clinical profile of the DOAC rivaroxaban is not affected by high weight or bariatric surgery; hence, it does not appear that rivaroxaban dosing needs to be altered in these patient populations.
Topics: Bariatric Surgery; Factor Xa Inhibitors; Humans; Obesity, Morbid; Practice Guidelines as Topic; Rivaroxaban; Thrombosis
PubMed: 28601546
DOI: 10.1016/j.amjmed.2017.05.011 -
Critical Care (London, England) Aug 2016Recently, a new generation of direct-acting oral anticoagulants (DOACs) with a greater specificity towards activated coagulation factors was introduced based on... (Review)
Review
BACKGROUND
Recently, a new generation of direct-acting oral anticoagulants (DOACs) with a greater specificity towards activated coagulation factors was introduced based on encouraging results for efficacy and safety in clinical studies. An initial limitation of these new drugs was the absence of an adequate strategy to reverse the effect if a bleeding event occurs or an urgent invasive procedure has to be carried out.
MAIN TEXT
Specific reversing agents for DOACs have become available, however, and are now evaluated in clinical studies. For the anti-factor Xa agents (rivaroxaban, apixaban, and edoxaban) a number of studies have shown that the administration of prothrombin complex concentrate resulted in a correction of the prolonged prothrombin time and restored depressed thrombin generation after rivaroxaban treatment in a controlled trial in healthy human subjects. In view of the relatively wide availability of prothrombin complex concentrates, this would be an interesting option if the results can be confirmed in patients on oral factor Xa inhibitors who present with bleeding complications. More specific reversal can be achieved with andexanet, a new agent currently in development that competitively binds to the anti-factor Xa agents. For the direct thrombin inhibitor dabigatran, the administration of prothrombin complex concentrates showed variable results in various volunteer trials and efficacy at relatively high doses in animal studies. Recently, a Fab fragment of a monoclonal antibody (idarucizumab) was shown to be an effective reversal agent for dabigatran in human studies.
CONCLUSION
For the new generation of DOACs, several reversal strategies and specific antidotes are under evaluation, although most interventions need further evaluation in clinical trials.
Topics: Administration, Oral; Anticoagulants; Disease Management; Factor Xa Inhibitors; Hemorrhage; Humans; Incidence; Prothrombin Time; Pyrazoles; Pyridines; Pyridones; Risk Factors; Rivaroxaban; Thiazoles
PubMed: 27543264
DOI: 10.1186/s13054-016-1413-3 -
Journal of the American College of... Jul 2021
Topics: Humans; Peripheral Arterial Disease; Rivaroxaban
PubMed: 34294269
DOI: 10.1016/j.jacc.2021.05.023 -
Clinical and Applied... Jul 2016Rivaroxaban, a direct factor Xa inhibitor, has been developed to meet clinical needs in a broad range of indications in adults: prevention of venous thromboembolism... (Review)
Review
BACKGROUND
Rivaroxaban, a direct factor Xa inhibitor, has been developed to meet clinical needs in a broad range of indications in adults: prevention of venous thromboembolism after elective hip or knee replacement surgery, treatment and secondary prevention of venous thromboembolism, prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation having one or more risk factors, and in Europe, prevention of atherothrombotic events after an acute coronary syndrome in patients with elevated cardiac biomarkers. However, the precise dose and regimen vary with the indication, leading to this effort to provide clarity concerning the appropriate use of rivaroxaban. This article reviews the clinical development program for rivaroxaban and summarizes the evidence for each approved, indication-specific dose regimen.
RESULTS
Although initially investigated for twice-daily dosing, early observations, including the finding that the pharmacodynamic effects of rivaroxaban last longer than the elimination half-life, suggested that once-daily dosing might be attainable and effective. These observations were evaluated within the extensive phase II program, which, together with pharmacology studies, provides the evidence underpinning the selection of once-daily regimens for most, but not all, of the approved clinical indications for rivaroxaban.
CONCLUSION
The evidence for each dosing regimen demonstrates that although pharmacology studies are of paramount importance, dose regimens must be subjected to careful empirical validation. Once-daily dosing was shown to be clinically appropriate for most rivaroxaban indications. Furthermore, a "one size fits all" approach to dosing frequency is unlikely to result in a regimen that yields optimal patient outcomes across different indications.
Topics: Adult; Cardiovascular Diseases; Clinical Trials as Topic; Dose-Response Relationship, Drug; Evidence-Based Medicine; Factor Xa Inhibitors; Humans; Rivaroxaban; Treatment Outcome
PubMed: 26893445
DOI: 10.1177/1076029616631427 -
Polish Archives of Internal Medicine Aug 2023Isolated distal deep vein thrombosis (IDDVT) is a frequent manifestation of venous thromboembolism (VTE), accounting for up to 50% cases of lower‑extremity deep vein... (Review)
Review
Isolated distal deep vein thrombosis (IDDVT) is a frequent manifestation of venous thromboembolism (VTE), accounting for up to 50% cases of lower‑extremity deep vein thrombosis (DVT). As compared with proximal DVT, IDDVT is more frequently associated with transient risk factors and less often occurs unprovoked or in the presence of permanent risk factors. IDDVT generally carries a significantly lower risk of proximal extension, post‑thrombotic syndrome, and recurrence than proximal DVT. Nevertheless, some patient subgroups, such as those with active cancer, other predisposing permanent risk factors, prior VTE, unprovoked IDDVT, persistently restricted mobility, and trifurcation or bilateral involvement, exhibit a non‑negligible recurrence risk. Unlike in proximal DVT, the optimal therapeutic management of IDDVT remains uncertain. In clinical practice, the vast majority of IDDVT patients are managed with anticoagulation rather than with surveillance serial compression ultrasonography, which tends to be reserved to individuals at a high bleeding risk. Available data seem to favor anticoagulant therapy over no anticoagulation, thanks to a significant reduction in the risk for proximal extension and recurrence, without increased bleeding risk. Recent results of the RIDTS (Rivaroxaban for the Treatment of Symptomatic Isolated Distal Deep Vein Thrombosis) randomized clinical trial with rivaroxaban further support the use of anticoagulant therapy for 3 months over shorter durations (eg, ≤6 weeks). In this review, we offer an updated overview of the epidemiology, risk factors, and clinical course of IDDVT, with a focus on the therapeutic management in light of current guideline recommendations and most recent evidence. We also present real‑life clinical cases of IDDVT with proposed therapeutic approaches, and highlight major challenges and gaps in this field.
Topics: Humans; Venous Thromboembolism; Rivaroxaban; Recurrence; Venous Thrombosis; Anticoagulants; Hemorrhage; Randomized Controlled Trials as Topic
PubMed: 37548526
DOI: 10.20452/pamw.16543 -
BMC Cardiovascular Disorders Jun 2023We evaluated the efficacy of the factor Xa inhibitor rivaroxaban on the differentiation ability of vascular endothelial progenitor cells (EPCs), which play roles in...
BACKGROUND
We evaluated the efficacy of the factor Xa inhibitor rivaroxaban on the differentiation ability of vascular endothelial progenitor cells (EPCs), which play roles in vascular injury repair and atherogenesis. Antithrombotic treatment in patients with atrial fibrillation undergoing percutaneous coronary intervention (PCI) is challenging, and current guidelines recommend oral anticoagulant monotherapy 1 year or more after PCI. However, biological evidence of the pharmacological effects of anticoagulants is insufficient.
METHODS
EPC colony-forming assays were performed using peripheral blood-derived CD34-positive cells from healthy volunteers. Adhesion and tube formation of cultured EPCs were assessed in human umbilical cord-derived CD34-positive cells. Endothelial cell surface markers were assessed using flow cytometry, and Akt and endothelial nitric oxide synthase (eNOS) phosphorylation were examined using western blot analysis of EPCs. Adhesion, tube formation and endothelial cell surface marker expression was observed in EPCs transfected with small interfering RNA (siRNA) against protease-activated receptor (PAR)-2. Finally, EPC behaviors were assessed in patients with atrial fibrillation undergoing PCI in whom warfarin was changed to rivaroxaban.
RESULTS
Rivaroxaban increased the number of large EPC colonies and increased the bioactivities of EPCs, including adhesion and tube formation. Rivaroxaban also increased vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, Tie-2, and E-selectin expression as well as Akt and eNOS phosphorylation. PAR-2 knockdown increased the bioactivities of EPCs and endothelial cell surface marker expression. Patients in whom the number of large colonies increased after switching to rivaroxaban showed better vascular repair.
CONCLUSIONS
Rivaroxaban increased the differentiation ability of EPCs, leading to potential advantages in the treatment of coronary artery disease.
Topics: Humans; Endothelial Progenitor Cells; Rivaroxaban; Factor Xa Inhibitors; Proto-Oncogene Proteins c-akt; Vascular Endothelial Growth Factor A; Atrial Fibrillation; Fibrinolytic Agents; Percutaneous Coronary Intervention; Cell Differentiation; Cells, Cultured; Cell Movement
PubMed: 37268884
DOI: 10.1186/s12872-023-03318-4 -
Europace : European Pacing,... Dec 2016Rivaroxaban is increasingly used in patients undergoing catheter ablation of atrial fibrillation (AF). In the absence of large controlled trials, a comprehensive... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of rivaroxaban compared with vitamin K antagonists for peri-procedural anticoagulation in catheter ablation of atrial fibrillation: a systematic review and meta-analysis.
Rivaroxaban is increasingly used in patients undergoing catheter ablation of atrial fibrillation (AF). In the absence of large controlled trials, a comprehensive meta-analysis of the literature appears to be the best way to obtain reliable evidence on rare peri-procedural outcomes such as thromboembolic or bleeding events. We aimed to provide a detailed analysis of currently available data on safety and efficacy of peri-procedural rivaroxaban in patients undergoing AF ablation. We performed a systematic search of the English language literature for studies comparing peri-procedural rivaroxaban therapy with vitamin K antagonists (VKAs) and reporting detailed data on bleeding and/or thromboembolic complications. The Peto odds ratio (POR) was used to pool data into a fixed-effect meta-analysis. A total of 7400 patients undergoing catheter ablation were included in 15 observational and 1 randomized studies of which 1994 were receiving rivaroxaban and 5406 VKA. The risk of thromboembolism trended to be lower in the rivaroxaban group [4/1954 vs. 19/5219, POR 0.40, 95% confidence interval (CI), 0.16-1.01, P = 0.052]. Major bleeding events occurred in 23 of 1994 cases (1.15%) in the rivaroxaban and 90 of 5406 (1.66%) in the VKA group (POR 0.74, 95% CI, 0.46-1.21, P = 0.23). A total of 87 minor bleeding events were reported in 1753 patients (4.96%) in the rivaroxaban group and in 165 of 4009 patients (4.12%) in the VKA group (POR 0.84, 95% CI 0.63-1.11, p = 0.22). In patients undergoing AF ablation, rivaroxaban appears to be an effective and safe alternative to VKA.
Topics: Anticoagulants; Atrial Fibrillation; Blood Coagulation; Catheter Ablation; Factor Xa Inhibitors; Hemorrhage; Humans; Rivaroxaban; Stroke; Thromboembolism; Vitamin K; Warfarin
PubMed: 26797248
DOI: 10.1093/europace/euv408 -
Hematology. American Society of... Dec 2016Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better... (Review)
Review
Direct oral anticoagulants (DOACs) have at least noninferior efficacy compared with other oral anticoagulants and have ancillary benefits, including overall better safety profiles, lack of the need for routine monitoring, rapid onset of action, and ease of administration. Reversal of these agents may be indicated in certain situations such as severe bleeding and for perioperative management. DOAC-associated bleeding should be risk stratified: patients with moderate or severe bleeding should have the DOAC discontinued and reversal strategies should be considered. Laboratory testing has limited utility in the acute management of bleeding; thrombin time and activated partial thromboplastin time may be useful for excluding clinically relevant levels of dabigatran. Prothrombin time is potentially useful for rivaroxaban and edoxaban, but calibrated anti-Xa assays are optimal for determining clinically relevant levels of factor Xa inhibitors. Because specific reversal agents are not widely available, supportive care and interventions for local hemostasis remain the cornerstones of therapy in the patient with DOAC-associated bleeding. Nonspecific reversal agents should be considered only in the event of severe bleeding because their efficacy is unknown, and they are associated with risk of thrombosis. Recent results from phase 3/4 studies demonstrate efficacy for an antidote to dabigatran (idarucizumab, a monoclonal antibody fragment with specificity for dabigatran) and an antidote to factor Xa inhibitors (andexanet alfa, a recombinant and inactive form of factor Xa that binds inhibitors). A universal reversal agent (ciraparantag) for many anticoagulants, including the DOACs, shows promise in results from phase 1 and 2 studies.
Topics: Administration, Oral; Antibodies, Monoclonal, Humanized; Anticoagulants; Antidotes; Dabigatran; Factor Xa; Hemorrhage; Humans; Partial Thromboplastin Time; Prothrombin Time; Recombinant Proteins; Rivaroxaban
PubMed: 27913536
DOI: 10.1182/asheducation-2016.1.612