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Journal of Market Access & Health Policy 2023To assess the comparative budget and health impact of lower-dose dabigatran versus reduced doses of apixaban and rivaroxaban in atrial fibrillation (AF) patients...
To assess the comparative budget and health impact of lower-dose dabigatran versus reduced doses of apixaban and rivaroxaban in atrial fibrillation (AF) patients eligible for a lower-/reduced-dose due to individual patient characteristics in the Netherlands. A budget impact model was developed in accordance with ISPOR guidelines. A 3-year-time horizon was considered, and analyses were conducted from a Dutch healthcare payer's perspective. The model applies published data to local AF-epidemiology, allowing calculations to estimate clinical events (strokes and haemorrhages) and costs. The analyses were based on real-world outcomes from patients with AF receiving a first direct oral anticoagulant (DOAC) prescription for low-dose dabigatran (110 mg) and a reduced dose of apixaban (2.5 mg) or rivaroxaban (15 mg). Two situations of switching treatments from one to another DOAC were modelled: switching from apixaban to dabigatran and from rivaroxaban to dabigatran. Base case results were given as savings per 100 patient-year, per total Dutch population, and events avoided. A univariate sensitivity analysis was conducted to explore the uncertainty around epidemiological and event costs input data. Scenario analyses were performed to estimate the effect of different market shares and potential price reductions due to future patent expiry for the total real-world population from the Netherlands. The 3-years outcomes of switching patients eligible for a lower-/reduced-dose due to individual patient characteristics from apixaban or rivaroxaban to dabigatran resulted in cost savings estimated at €157 or €72 thousand per 100 patient-years, respectively, or €146 million per total Dutch population. Looking into the clinical events, dabigatran reflected the lowest number of mortalities, ischemic strokes, major bleeding, non-major bleeding, and haemorrhagic stroke compared to apixaban and rivaroxaban. The sensitivity analysis consistently reflected cost savings, with the ischeamic stroke events having the biggest impact. Accounting for the Dutch situation, both scenarios showed total savings ranging from €45 to €229 million over 3 years. Switching eligible AF-patients from reduced-dose apixaban or rivaroxaban to lower-dose dabigatran has the potential to reduce healthcare payer's budget expenditures and provide health gains. Cost savings can potentially be further enhanced by market share adjustments and further price reductions.
PubMed: 37675057
DOI: 10.1080/20016689.2023.2247719 -
Journal of Multidisciplinary Healthcare 2023To investigate the safety and effectiveness of cryo-balloon pulmonary vein isolation (PVI) and left atrial appendage closure (LAAC) combined procedure and half-dose...
Safety and Efficacy of Cryoballoon Pulmonary Vein Isolation and Left Atrial Appendage Closure Combined Procedure and Half-Dose Rivaroxaban After Operation in Elderly Patients with Atrial Fibrillation.
BACKGROUND
To investigate the safety and effectiveness of cryo-balloon pulmonary vein isolation (PVI) and left atrial appendage closure (LAAC) combined procedure and half-dose rivaroxaban after operation in elderly patients with atrial fibrillation (AF).
PATIENTS AND METHODS
A total of 203 AF patients presented for cryo-balloon PVI, and LAAC combined procedure was included from 2019 to 2021. Postoperative patients were anticoagulated with rivaroxaban with/without clopidogrel for 60 days, with oral rivaroxaban of 10 mg in the elderly group and 20 mg in the non-elderly group. Patients with AF ≥80 and <80 years were considered elderly and non-elderly groups, respectively. Scheduled follow-ups and transesophageal echocardiography were used to assess peri- and post-procedural safety and effectiveness.
RESULTS
A total of 203 patients underwent the combined procedure, 83 in the elderly and 120 in the non-elderly groups. All patients successfully obtained PVI and satisfactory LAAC. During the perioperative period, one patient had puncture complications in the elderly group and one with thrombosis in the non-elderly group. Oral rivaroxaban was administered to 83.2% and 75% of patients in the elderly and non-elderly groups, respectively, and rivaroxaban was combined with clopidogrel anticoagulation in the remaining patients. The annual rates of composite clinical events were 8.4% and 9.2% in the elderly and non-elderly groups, respectively, with no statistically significant difference. Patients in both groups had complete sealing, and there was no displacement of devices, death and peripheral arterial thrombosis. Recurrence of AF occurred in 25 and 32 patients in the elderly and non-elderly groups, respectively, with no statistically significant difference. Besides, the two groups had no statistically significant difference in cerebral infarction/transient ischemic attack and device-related thrombosis (p > 0.05).
CONCLUSION
This study suggests that cryo-balloon PVI and LAAC combined procedure and half-dose rivaroxaban after the operation is safe and effective in treating elderly patients with AF.
PubMed: 37693855
DOI: 10.2147/JMDH.S424843 -
Cureus Feb 2024An effective anticoagulation therapy is required for patients with atrial fibrillation because it presents a significant risk of stroke. The current study evaluates the... (Review)
Review
An effective anticoagulation therapy is required for patients with atrial fibrillation because it presents a significant risk of stroke. The current study evaluates the relative safety as well as efficacy of rivaroxaban in patients who are diagnosed with atrial fibrillation. A thorough literature review of relevant databases was conducted, focusing on academic and clinical studies that were published from 2017 onward. Inclusion criteria comprised randomized controlled trials and other observational studies comparing the incidence of stroke and the safety index of rivaroxaban in atrial fibrillation. We followed the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) for data overview reporting and overview. A total of 21 studies were selected based on the inclusion criteria. A total of 19/21 studies advocated the adoption of rivaroxaban for minimizing stroke incidence. Rivaroxaban also showed superiority in achieving the therapeutic objectives, i.e., reduction in the incidence of stroke. The results for rivaroxaban against warfarin showed an improved safety index and effectiveness of rivaroxaban. The total effect size for the analysis was calculated to be Z=2.62 (p-value=0.009). The individual effect of all studies favored the "rivaroxaban" group. The heterogeneity in the study was as follows: tau=0.10; chi=110.10, df=6; I=95%. The second analysis for risk reduction and incidence of stroke after rivaroxaban therapy also showed a bias towards rivaroxaban therapy. The combined effect for the analysis was found to be as follows: HR=0.73 ((95% CI: 0.50, 1.07). The total effect was calculated to be Z=1.61 (p-value= 0.10). The heterogeneity was found to be as follows: tau= 0.20, chi=89.97, df=6, I=93%. Standard dosing of rivaroxaban emerges as a preferred strategy for stroke prevention, balancing efficacy and safety. Clinical decision-making should consider individual patient characteristics and future research should delve into specific subpopulations and long-term outcomes to further refine treatment guidelines.
PubMed: 38496142
DOI: 10.7759/cureus.54252 -
Cureus Sep 2023Direct oral anticoagulants (DOACs) have shifted the landscape of anticoagulation over the past decade, becoming a frequently used pharmaceutical agent. The increased use...
Direct oral anticoagulants (DOACs) have shifted the landscape of anticoagulation over the past decade, becoming a frequently used pharmaceutical agent. The increased use of DOACs for long-term anticoagulation has led to a rise in reported anticoagulant-related adverse reactions, such as anticoagulant-related nephropathy (ARN). The occurrence of ARN is well reported with warfarin; however, there are few cases of ARN reported with DOAC use. We report the case of an elderly man with coronary artery disease and hypertension who was initiated on apixaban for atrial fibrillation three years prior to presentation but developed rapid renal decline over the six months prior to presentation. The estimated glomerular filtration rate (eGFR) had decreased precipitously from 48 mL/min/1.73 m to 19 mL/min/1.73 m with a concurrent drop in hemoglobin in the setting of persistent microscopic hematuria. A renal biopsy showed red blood cell casts consistent with glomerular hematuria, despite no crescents or signs of other forms of glomerulonephritis. The patient's renal function ceased to deteriorate and had a 35% recovery (serum creatinine 2.6 mg/dL, eGFR 25 mL/min/1.73 m) after the discontinuation of apixaban and conversion to rivaroxaban without the use of corticosteroids. The patient reported at follow-up that he discontinued rivaroxaban four days after initiation on his own accord due to extrarenal bleeding. Our case highlights the importance of prompt recognition and treatment of the underreported but potentially significant incidence of ARN with apixaban in a patient with an otherwise unexplained kidney injury.
PubMed: 37799236
DOI: 10.7759/cureus.44672 -
Annals of Medicine and Surgery (2012) Apr 2024Cerebral venous thromboembolism (CVT) poses a significant risk of venous infarction and haemorrhage, which can lead to neurological deficits and, in severe cases, even... (Review)
Review
BACKGROUND
Cerebral venous thromboembolism (CVT) poses a significant risk of venous infarction and haemorrhage, which can lead to neurological deficits and, in severe cases, even death. The optimal treatment regimen for patients with CVT remains unclear.
METHODS
MEDLINE, Embase, Google Scholar, Web of Science (WoS), and Cochrane Central databases were searched for randomized controlled trials (RCTs) and observational studies assessing the efficacy and safety of rivaroxaban in patients with CVT. All-site venous thromboembolism (VTE), risk of clinically relevant non-major bleeding, incidence of partial recanalization, complete recanalization and major haemorrhage were among outcomes of interest. Mantel-Haenszel weighted random-effects model was used to calculate relative risks (RRs) with 95% CIs.
RESULTS
The analysis included 1 RCT and 3 observational studies containing 211 patients. Compared to vitamin K antagonists (VKAs), rivaroxaban did not significantly decrease the all-site VTE [RR 0.31 (95% CI 0.01, 8.43); =0.49, I=0%]. Compared with VKAs, patients on rivaroxaban did not show a significantly reduced risk of recurrent cerebral venous thrombosis. In terms of incidence of partial recanalization, there was no discernible difference between rivaroxaban and VKAs [RR 0.90 (95% CI 0.66, 1.22); =0.49, I=0%]. There was no discernible difference in incidence of complete recanalization [RR 0.98 (95% CI 0.32, 3.03); =0.97, I=28%] and incidence of major haemorrhage [RR 0.19 (95% CI 0.01, 4.54); =0.30].
CONCLUSION
Rivaroxaban was found to have similar efficacy to VKAs. Due to its lower risk of severe bleeding and no need for INR monitoring, rivaroxaban may be a preferable treatment option for CVT.
PubMed: 38576935
DOI: 10.1097/MS9.0000000000001689 -
Medicine Sep 2023Possible challenges in dosing non-vitamin K antagonist oral anticoagulants in nonvalvular atrial fibrillation (NVAF) and limited evidence in Saudi Arabia make it...
Possible challenges in dosing non-vitamin K antagonist oral anticoagulants in nonvalvular atrial fibrillation (NVAF) and limited evidence in Saudi Arabia make it difficult to assess their appropriateness. This study aimed to assess the appropriateness of prescribing rivaroxaban and apixaban in hospitalized patients with newly diagnosed NVAF. This single-center, descriptive, retrospective study was conducted at a tertiary hospital in Saudi Arabia between December 2018 and December 2019. The included patients were aged 18 years and older with newly diagnosed NVAF who received either rivaroxaban or apixaban during hospitalization. The primary outcome was the dosing appropriateness of rivaroxaban and apixaban in NVAF based on recent food and drug administration prescribing guidelines. Descriptive statistics including frequencies and percentages as well as mean ± standard deviation was used to summarize the data. Pearson Chi-square was used to test for significant difference in proportions of appropriate and inappropriate dosing. Pearson Correlation was used to test for associations between underdosing and overdosing with other patients characteristics. A priori P value < .05 was considered significant throughout. A total of 203 patients were included in our analysis. Majority of the patients {125 (61.6%), P = .001} received rivaroxaban. Overall, the dosing appropriateness observed in 143 (70.5%) of the patients who received the rivaroxaban and apixaban was significantly higher than the dosing inappropriateness observed in 60 (29.5%) of the patients who received the same drugs, P < .001. Apixaban had the highest proportion of patients, 45 (57.7%) with dosing inappropriateness. Overall, underdosing was the most common dosing inappropriateness observed in 53 (26.1%) of the patients. There was a significant negative correlation between the drugs underdosing and creatinine clearance, r = -0.223, P = .001. The findings in our present study showed that majority of the patients received appropriate dosing of rivaroxaban and apixaban in hospitalized patients with NVAF. Healthcare providers should update themselves with the recent dosing recommendations for the non-vitamin K-antagonist oral anticoagulants in NVAF to further improve the dosing appropriateness in hospitalized patients with NVAF.
Topics: United States; Humans; Atrial Fibrillation; Rivaroxaban; Retrospective Studies; Tertiary Care Centers; Anticoagulants
PubMed: 37682197
DOI: 10.1097/MD.0000000000035058 -
Clinical Research in Cardiology :... Nov 2023COVID-19 is associated with a prothrombotic state. Current guidelines recommend prophylactic anticoagulation upon hospitalization. (Randomized Controlled Trial)
Randomized Controlled Trial
Initial therapeutic anticoagulation with rivaroxaban compared to prophylactic therapy with heparins in moderate to severe COVID-19: results of the COVID-PREVENT randomized controlled trial.
BACKGROUND
COVID-19 is associated with a prothrombotic state. Current guidelines recommend prophylactic anticoagulation upon hospitalization.
METHODS
COVID-PREVENT, an open-label, multicenter, randomized, clinical trial enrolled patients (≥ 18 years) with moderate to severe COVID-19 and age-adjusted D-dimers > 1.5 upper limit of normal (ULN). The participants were randomly assigned (1:1) to receive either therapeutic anticoagulation with rivaroxaban 20 mg once daily or thromboprophylaxis with a heparin (SOC) for at least 7 days followed by prophylactic anticoagulation with rivaroxaban 10 mg once daily for 28 days or no thromboprophylaxis. The primary efficacy outcome was the D-dimer level and the co-primary efficacy outcome the 7-category ordinal COVID-19 scale by WHO at 7 days post randomization. The secondary outcome was time to the composite event of either venous or arterial thromboembolism, new myocardial infarction, non-hemorrhagic stroke, all-cause death or progression to intubation and invasive ventilation up to 35 days post randomization.
RESULTS
The primary efficacy outcome D-dimer at 7 days was not different between patients assigned to therapeutic (n = 55) or prophylactic anticoagulation (n = 56) (1.21 mg/L [0.79, 1.86] vs 1.27 mg/L [0.79, 2.04], p = 0.78). In the whole study population D-dimer was significantly lower at 7 days compared to baseline (1.05 mg/L [0.75, 1.48] vs 1.57 mg/L [1.13, 2.19], p < 0.0001). Therapy with rivaroxaban compared to SOC was not associated an improvement on the WHO 7-category ordinal scale at 7 days (p = 0.085). Rivaroxaban improved the clinical outcome measured by the score in patients with a higher baseline D-dimer > 2.0 ULN (exploratory analysis; 0.632 [0.516, 0.748], p = 0.026). The secondary endpoint occurred in 6 patients (10.9%) in the rivaroxaban group and in 12 (21.4%) in the SOC group (time-to-first occurrence of the components of the secondary outcome: HR 0.5; 95% CI 0.15-1.67; p = 0.264). There was no difference in fatal or non-fatal major or clinically relevant non-major bleeding between the groups.
CONCLUSIONS
Therapeutic anticoagulation with rivaroxaban compared to prophylactic anticoagulation with a heparin did not improve surrogates of clinical outcome in patients with moderate to severe COVID-19. Whether initial rivaroxaban at therapeutic doses might be superior to thromboprophylaxis in patients with COVID-19 and a high risk as defined by D-dimer > 2 ULN needs confirmation in further studies.
Topics: Humans; COVID-19; Rivaroxaban; Anticoagulants; SARS-CoV-2; Venous Thromboembolism; Heparin; Treatment Outcome
PubMed: 37407731
DOI: 10.1007/s00392-023-02240-1 -
Heliyon Nov 2023Current observational studies have compared the effectiveness and safety of edoxaban with other oral anticoagulants in patients with AF, but the results are still... (Review)
Review
BACKGROUND AND AIM
Current observational studies have compared the effectiveness and safety of edoxaban with other oral anticoagulants in patients with AF, but the results are still disputed. This meta-analysis was conducted to compare the effect of edoxaban in patients with AF.
METHODS
We performed systematic research from the PubMed, EMBASE, and Cochrane Library databases until November 2022 to obtain relevant observational studies. Adjusted risk ratios (RRs) and 95 % confidence intervals (CIs) of the outcomes were collected and pooled by a random-effects model. This study was prospectively registered in PROSPERO (CRD42022314222).
RESULTS
A total of 17 observational studies were included in this meta-analysis. Compared with vitamin K antagonists, edoxaban was associated with lower risks of stroke or systemic embolism (RR = 0.67, 95 % CI:0.61-0.74), major bleeding (RR = 0.54, 95 % CI:0.44-0.67), and intracranial hemorrhage (RR = 0.51, 95 % CI:0.29-0.90). Compared with dabigatran or rivaroxaban, edoxaban was associated with reduced risks of stroke or systemic embolism (dabigatran [RR = 0.76, 95 % CI:0.66-0.87]; rivaroxaban [RR = 0.81, 95 % CI:0.70-0.94]) and major bleeding (dabigatran [RR = 0.82, 95 % CI:0.69-0.98]; rivaroxaban [RR = 0.81, 95 % CI:0.70-0.94]). Compared with apixaban, edoxaban was associated with a reduced risk of stroke or systemic embolism (RR = 0.87, 95 % CI:0.79-0.97), but had similar risks of bleeding events.
CONCLUSIONS
Our current evidence suggested that edoxaban might have superior effectiveness and/or safety outcomes than vitamin K antagonists, dabigatran, rivaroxaban, and apixaban for stroke prevention in patients with AF.
PubMed: 38027839
DOI: 10.1016/j.heliyon.2023.e21740 -
Clinical and Translational Science Mar 2024Administration of oral medicinal products as crushed tablets or open capsules is an important delivery option for patients suffering from dysphagia. To obtain full... (Review)
Review
Administration of oral medicinal products as crushed tablets or open capsules is an important delivery option for patients suffering from dysphagia. To obtain full interchangeability of generics with the original products, demonstration of bioequivalence (BE) between both products administered as crushed tablets/open capsules was required for poorly soluble product by European Medicines Agency (EMA) at the time of development of our rivaroxaban and deferasirox generic products. We present the results of two BE studies with modified administration of these products, which compared relative bioavailability between generic and reference products. In the rivaroxaban study, the test product was administered as a capsule sprinkled on and mixed with applesauce, whereas the reference tablet was crushed and administered with applesauce under fed conditions. In the deferasirox study, both treatments were administered as crushed tablets under fasting conditions. Both studies applied a two-way crossover design and were conducted after a single-dose in healthy volunteers. The 90% confidence interval of the geometric mean ratio area under the analyte concentration versus time curve, from time zero to the time of the last measurable analyte concentration and maximum measured analyte concentration over the sampling period of the test to reference ratio were 103.36-110.37% and 97.98-108.45% for rivaroxaban, respectively, and 96.69-107.29% and 94.19-109.45% for deferasirox, respectively. Thus, the BE criteria (80.00-125.00%) were met in both studies which demonstrated that bioavailability was not affected when the test and reference products were administered in the form of crushed tablet/open capsule. These results support the argument of redundancy of crushed product studies for poorly soluble drugs, which is in line with the currently revised position of the EMA on this topic.
Topics: Humans; Therapeutic Equivalency; Rivaroxaban; Deferasirox; Administration, Oral; Tablets; Drugs, Generic
PubMed: 38511529
DOI: 10.1111/cts.13752 -
Frontiers in Pharmacology 2023venous thromboembolism (VTE) is one of the most common complications after major orthopaedic surgery. Recent studies have suggested that aspirin may also be effective...
Comparison of efficacy and safety between aspirin and oral anticoagulants for venous thromboembolism prophylaxis after major orthopaedic surgery: a meta-analysis of randomized clinical trials.
venous thromboembolism (VTE) is one of the most common complications after major orthopaedic surgery. Recent studies have suggested that aspirin may also be effective in preventing VTE, but it is still controversial whether it can be routinely used. To compare the efficacy and safety of aspirin against oral anticoagulants in the prevention of VTE following total hip arthroplasty (THA), total knee arthroplasty (TKA) or hip fracture surgery (HFS). Relevant publications have been obtained using electronic search databases such as PubMed, Embase, Web of Science, Cochrane Library, and Clinical Trials. gov. from inception to 20 July 2023. Only RCTs evaluating the efficacy and safety of aspirin compared with oral anticoagulants undergoing major orthopaedic surgery were included in the meta-analysis. The primary outcome reported was any VTE event (including deep vein thrombosis (DVT) and pulmonary embolism (PE)). Secondary outcomes included mortality, major bleeding (including gastrointestinal bleed, cerebrovascular hemorrhage, or any bleeding requiring a return to the theater), minor bleeding (ecchymosis, epistaxis, hematuria), and wound complications. The risk of bias for all included studies was assessed according to the Cochrane Collaboration's tool. After screening 974 studies, 12 randomized clinical trials (RCTs) were included, involving 5,088 participants, including 2,540 participants in aspirin, 2,205 participants in rivaroxaban, and 323 participants in warfarin. Aspirin was found to be less effective than oral anticoagulants in thromboprophylaxis after major orthopedic surgery (RR = 1.206, 95% CI 1.053-1.383). After subgroup analysis according to the type of oral anticoagulant, the results showed that aspirin was similar to rivaroxaban and inferior to warfarin. Considering that the studies in the warfarin group were all conducted before 2000, our results need to be further confirmed. In addition, the aspirin group had a higher risk of VTE than the control group in other subgroups, including a follow-up time of ≤3 months, type of procedure as TKA, high-dose aspirin (≥650 mg qd), and no combined use of mechanical prophylaxis. In terms of safety events, aspirin did not show significant differences in major bleeding (RR = 0.952, 95% CI 0.499-1.815), all-cause mortality (RR = 1.208, 95% CI 0.459-3.177), and wound-related events (RR = 0.618, 95% CI 0.333-1.145) compared with oral anticoagulants, and aspirin was associated with a reduction in the risk of minor bleeding (RR = 0.685, 95% CI 0.552-0.850) events and total bleeding (RR = 0.726, 95% CI 0.590-0.892). Aspirin reduces bleeding risk after major orthopedic surgery compared with oral anticoagulants, but may sacrifice VTE prevention to some extent. Updated evidence is needed to analyze the thromboprophylaxis effects of aspirin in patients undergoing major orthopedic surgery. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=463481, identifier CRD42023463481.
PubMed: 38259284
DOI: 10.3389/fphar.2023.1326224