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Drug Design, Development and Therapy 2023Direct oral anticoagulants (DOACs) are widely used for stroke prevention in atrial fibrillation. However, they have a bleeding complication. Breast cancer resistance...
PURPOSE
Direct oral anticoagulants (DOACs) are widely used for stroke prevention in atrial fibrillation. However, they have a bleeding complication. Breast cancer resistance protein, encoded by , is known to be an efflux transporter of apixaban and rivaroxaban among DOACs. This study aimed to investigate the association between gene variants and bleeding complications during treatment with ABCG2 substrates (apixaban and rivaroxaban).
PATIENTS AND METHODS
Patients treated with apixaban and rivaroxaban were enrolled from June 2018 to December 2021. Five single nucleotide polymorphisms (SNPs) of were selected. Previously studied genes (, and ) were further analyzed as possible confounders. Finally, a total of 16 SNPs were examined in this case-control study. The outcome was defined as major bleeding and clinically relevant non-major bleeding. Two models were constructed using the multivariable analysis.
RESULTS
Among 293 patients, 64 were cases. The mean age of the patients was 68.8 years, and males comprised 62.5% of the study population. Model I revealed that a history of bleeding, concurrent use of proton pump inhibitor (PPI), rs3114018, and rs1045642 were significantly associated with bleeding complications; the AORs (95% CI) were 6.209 (2.210-17.442), 2.385 (1.064-5.349), 2.188 (1.156-4.142), and 3.243 (1.371-7.671), respectively. Model II showed that modified HAS-BLED score, concurrent use of PPI, rs3114018, and rs1045642 were significantly associated with bleeding complications.
CONCLUSION
The modified HAS-BLED score, a history of bleeding, concurrent use of PPI, rs3114018, and rs1045642 were significantly associated with the risk of bleeding complications in patients on apixaban and rivaroxaban, after adjusting for other confounders. These findings can be used to develop individualized treatment strategies for patients taking apixaban and rivaroxaban.
Topics: Male; Humans; Aged; Female; Rivaroxaban; ATP Binding Cassette Transporter, Subfamily G, Member 2; Case-Control Studies; Neoplasm Proteins; Polymorphism, Single Nucleotide
PubMed: 37641689
DOI: 10.2147/DDDT.S417096 -
American Journal of Cardiovascular... Jan 2024Rivaroxaban 2.5 mg twice daily with aspirin 100 mg daily was shown to be better than aspirin 100 mg daily for preventing cardiovascular (CV) death, stroke or myocardial... (Clinical Trial)
Clinical Trial
BACKGROUND
Rivaroxaban 2.5 mg twice daily with aspirin 100 mg daily was shown to be better than aspirin 100 mg daily for preventing cardiovascular (CV) death, stroke or myocardial infarction in patients with either stable coronary artery disease (CAD) or peripheral artery disease (PAD). The cost-effectiveness of this regimen in this population is essential for decision-makers to know.
METHODS
US direct healthcare system costs (in USD) were applied to hospitalized events, procedures and study drugs utilized by all patients. We determined the mean cost per participant for the full duration of the trial (mean follow-up of 23 months) plus quality-adjusted life years (QALYs) and the incremental cost-effectiveness ratio (ICER) over a lifetime using a two-state Markov model with 1-year cycle length. Sensitivity analyses were performed on the price of rivaroxaban and the annual discontinuation rate.
RESULTS
The costs of events and procedures were reduced for Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) patients who received rivaroxaban 2.5 mg orally (BID) plus acetylsalicylic acid (ASA) compared with ASA alone. Total costs were higher for the combination group ($7426 versus $4173) after considering acquisition costs of the study drug. Over a lifetime, patients receiving rivaroxaban plus ASA incurred $27,255 more and gained 1.17 QALYs compared with those receiving ASA alone resulting in an ICER of $23,295/QALY. ICERs for PAD only and polyvascular disease subgroups were lower.
CONCLUSION
Rivaroxaban 2.5 mg BID plus ASA compared with ASA alone was cost-effective (high value) in the USA. COMPASS ClinicalTrials.gov identifier: NCT01776424.
Topics: Humans; Aspirin; Cost-Benefit Analysis; Drug Therapy, Combination; Factor Xa Inhibitors; Myocardial Infarction; Peripheral Arterial Disease; Rivaroxaban; Stroke
PubMed: 38153624
DOI: 10.1007/s40256-023-00620-6 -
American Journal of Nephrology 2016
Topics: Anticoagulants; Atrial Fibrillation; Factor Xa Inhibitors; Humans; Kidney Failure, Chronic; Practice Guidelines as Topic; Renal Dialysis; Rivaroxaban; Thromboembolism; Venous Thrombosis
PubMed: 27100995
DOI: 10.1159/000445329 -
Tissue Barriers Oct 2021Rivaroxaban is one of the direct factor Xa inhibitors. Its function in the inactivated coagulation cascade is unclear. The aim of the study was to assess the effect of...
BACKGROUND
Rivaroxaban is one of the direct factor Xa inhibitors. Its function in the inactivated coagulation cascade is unclear. The aim of the study was to assess the effect of rivaroxaban on the endothelial integrity and inflammatory properties of endothelial cells stimulated by 25-hydroxycholesterol (25-OHC).
METHODS
HUVECs were stimulated with 25-OHC, rivaroxaban and 25-OHC+ rivaroxaban. HUVEC integrity and permeability were measured using the xCELLigence system and paracellular flux assay. The mRNA expression of tissue factor, ICAM-1, VEGF, IL-33, MCP-1, TNF-α was analyzed in the real-time PCR. Apoptosis and viability were measured by flow cytometry. The VEGF protein concentration was assessed by ELISA. The confocal microscope was used to evaluate the expression of VE-cadherin in endothelial cells.
RESULTS
25-OHC decreased endothelial cell integrity and increased the mRNA expression of IL-33, tissue factor, ICAM-1, MCP-1, VEGF, TNF-α as compared to unstimulated controls. Following the stimulation with rivaroxaban, HUVEC restored integrity disrupted by 25-OHC ( < .01). In HUVECs pre-stimulated with oxysterol, rivaroxaban decreased mRNA expression of IL-33, TNF-α, chemokines MCP-1, ICAM-1, VEGF and tissue factor ( < .01). Rivaroxaban 100 mg/ml+25-OHC increased the VE-cadherin expression in endothelium as compared to 25-OHC ( < .05).
CONCLUSION
Our finding suggests that rivaroxaban may restore the endothelial barrier and inhibit the inflammatory activation caused by oxysterol .
Topics: Endothelium, Vascular; Human Umbilical Vein Endothelial Cells; Humans; Oxysterols; Rivaroxaban
PubMed: 34323663
DOI: 10.1080/21688370.2021.1956284 -
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 -
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 -
Cardiovascular Therapeutics 2021Direct oral anticoagulants (DOACs) are widely used for the prevention of stroke in nonvalvular atrial fibrillation, treatment of deep venous thrombosis and pulmonary... (Review)
Review
Direct oral anticoagulants (DOACs) are widely used for the prevention of stroke in nonvalvular atrial fibrillation, treatment of deep venous thrombosis and pulmonary embolism, and as prophylaxis after hip and knee surgery after approval by the Food and Drug Administration. In the last decade, DOACs were studied for various indications; this review is focused on rivaroxaban, a factor Xa inhibitor, which is used in an expanded evidence-based fashion for coronary artery disease, peripheral artery disease, heart failure, malignancy, and prophylaxis of deep venous thrombosis in acute medical illnesses.
Topics: Cardiovascular Diseases; Clinical Decision-Making; Factor Xa Inhibitors; Hemorrhage; Humans; Patient Selection; Risk Factors; Rivaroxaban; Treatment Outcome
PubMed: 33505518
DOI: 10.1155/2021/8886210 -
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 Oct 2023Despite availability of effective preventive therapies based on guidelines, patients with vascular diseases continue to be at a high risk for recurrent ischemic events.... (Review)
Review
Despite availability of effective preventive therapies based on guidelines, patients with vascular diseases continue to be at a high risk for recurrent ischemic events. Therefore, novel therapeutic strategies are required to further reduce the residual risk present in these patients. Platelet aggregation and fibrin organization are involved in arterial thrombosis. Rivaroxaban is capable of targeting both processes and has a synergistic effect when used in combination with acetylsalicylic acid (ASA), providing the so‑called dual pathway inhibition (DPI). The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial showed that the DPI (a combination of rivaroxaban at 2.5 mg twice daily [vascular dose] and ASA at 100 mg once daily) reduced cardiovascular death, stroke, or myocardial infarction by 24% in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD). Subsequently, the VOYAGER PAD (Vascular Outcomes Study of ASA Along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) trial confirmed the effectiveness of the vascular dose of rivaroxaban in patients with PAD after lower‑extremity revascularization, as compared with ASA alone. Therefore, DPI is recommended in the patients with CAD (+/- PAD) or symptomatic PAD at a high risk of ischemia. The purpose of this review is to examine the clinical benefits and practical implications of DPI in the CAD and PAD patients.
Topics: Humans; Rivaroxaban; Cardiovascular Diseases; Platelet Aggregation Inhibitors; Outpatients; Factor Xa Inhibitors; Drug Therapy, Combination; Aspirin; Peripheral Arterial Disease; Ischemia
PubMed: 37738024
DOI: 10.20452/pamw.16566 -
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