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1.
Geroscience ; 46(1): 923-944, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37261677

ABSTRACT

Balancing stroke prevention and risk of bleeding in patients with atrial fibrillation (AF) is challenging. Direct oral anticoagulants (DOACs) are by now considered standard of care for treating patients with AF in international guidelines. Our objective was to assess the safety of long-term intake of DOACs in older adults with AF. We included RCTs in elderly (≥ 65 years) patients with AF. A systematic search in MEDLINE and EMBASE was performed on 19 April 2022. For determination of risk of bias, the RoB 2 tool was applied. We pooled outcomes using random-effects meta-analyses. The quality of evidence was assessed using GRADE. Eleven RCTs with a total of 63,374 patients were identified. Two RCTs compared apixaban with either warfarin or aspirin, four edoxaban with either placebo, aspirin, or vitamin K antagonists (VKAs), two dabigatran with warfarin and three rivaroxaban with warfarin. DOACs probably reduce mortality in elderly patients with AF (HR 0.89 95%CI 0.77 to 1.02). Low-dose DOACs likely reduce bleeding compared to VKAs (HR ranged from 0.47 to 1.01). For high-dose DOACS the risk of bleeding varied widely (HR ranged from 0.80 to 1.40). We found that low-dose DOACs probably decrease mortality in AF patients. Moreover, apixaban and probably edoxaban are associated with fewer major or clinically relevant bleeding (MCRB) events compared to VKAs. For dabigatran and rivaroxaban, the risk of MCRB varies depending on dose. Moreover, subgroup analyses indicate that in the very old (≥ 85) the risk for MCRB events might be increased when using DOACs.Registration: PROSPERO: CRD42020187876.


Subject(s)
Atrial Fibrillation , Pyridines , Thiazoles , Humans , Aged , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Warfarin/adverse effects , Rivaroxaban/therapeutic use , Dabigatran/therapeutic use , Randomized Controlled Trials as Topic , Anticoagulants/adverse effects , Hemorrhage/chemically induced , Hemorrhage/complications , Hemorrhage/drug therapy , Aspirin/therapeutic use
2.
Biomed Pharmacother ; 170: 116018, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38113628

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most fatal solid malignancies worldwide. Evidence suggests that thrombin stimulates tumor progression via fibrin formation and platelet activation. Meanwhile, we also found a correlation between thrombin and HCC through bioinformatics analysis. Dabigatran is a selective, direct thrombin inhibitor that reversibly binds to thrombin. Dabigatran was used as the lead agent in this study, and 19 dabigatran derivatives were designed and synthesized based on docking mode. The thrombin-inhibitory activity of the derivative AX-2 was slightly better than that of dabigatran. BX-2, a prodrug of AX-2, showed a fairly strong inhibitory effect on thrombin-induced platelet aggregation, and effectively antagonized proliferation of HCC tumor cells induced by thrombin at the cellular level. Furthermore, BX-2 reduced tumor volume, weight, lung metastasis, and secondary tumor occurrence in nude mouse models. BX-2 combined with sorafenib increased sorafenib efficacy. This study lays the foundation for discovering new anti-HCC mechanism based on thrombin. BX-2 can be used as an anti-HCC drug lead for further research.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Mice , Animals , Dabigatran/pharmacology , Dabigatran/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Thrombin/metabolism , Sorafenib/pharmacology , Liver Neoplasms/drug therapy
3.
J Am Heart Assoc ; 12(23): e030380, 2023 Dec 05.
Article in English | MEDLINE | ID: mdl-38014696

ABSTRACT

BACKGROUND: Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain. METHODS AND RESULTS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the PubMed, EMBASE, and Cochrane databases for randomized controlled trials that compared thromboembolic or bleeding outcomes between a direct oral anticoagulant (DOAC) and a vitamin K antagonist (VKA) and reported outcomes for patients aged ≥75 years with atrial fibrillation. The efficacy outcome was the composite of stroke and systemic embolism. Safety outcomes included major bleeding, any clinically relevant bleeding, and intracranial hemorrhage. Each DOAC and VKA was compared pairwise in a network meta-analysis. High- and low-dose regimens and factor IIa and Xa inhibitors were also compared. Seven randomized controlled trials were included in the analysis. Stroke and systemic embolism risks did not differ significantly among DOACs. There were no significant differences in major bleeding between each DOAC and VKA. Intracranial hemorrhage risk was significantly lower with dabigatran, apixaban, and edoxaban than with VKA and rivaroxaban, which had similar risks. High-dose regimens led to lower risks of stroke or systemic embolism compared with VKA and low-dose regimens, with both doses having similar bleeding risks. CONCLUSIONS: In patients aged ≥75 years with atrial fibrillation, DOACs were associated with fewer thromboembolic events compared with VKA, whereas dabigatran, apixaban, and edoxaban were associated with lower risks of intracranial hemorrhage compared with VKA and rivaroxaban. REGISTRATION: URL: www.crd.york.ac.uk/prospero/. Unique identifier: CRD42022329557.


Subject(s)
Atrial Fibrillation , Embolism , Stroke , Humans , Aged , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/chemically induced , Rivaroxaban/adverse effects , Dabigatran/therapeutic use , Network Meta-Analysis , Randomized Controlled Trials as Topic , Anticoagulants/therapeutic use , Stroke/prevention & control , Stroke/complications , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Embolism/prevention & control , Intracranial Hemorrhages/chemically induced , Intracranial Hemorrhages/epidemiology , Intracranial Hemorrhages/complications , Administration, Oral
4.
Turk Kardiyol Dern Ars ; 51(2): 88-96, 2023 03.
Article in English | MEDLINE | ID: mdl-36916815

ABSTRACT

OBJECTIVE: Oral anticoagulant therapy is the cornerstone of atrial fibrillation management to prevent stroke and systemic embolism. However, there is limited real-world information regarding stroke and systemic embolism prevention strategies in patients with atrial fibrillation. The aim of the ROTA study is to obtain the real-world data of anticoagulant treatment patterns in patients with atrial fibrillation. METHODS: The ROTA study is a prospective, multicenter, and observational study that included 2597 patients with atrial fibrillation. The study population was recruited from 41 cardiology outpatient clinics between January 2021 and May 2021. RESULTS: The median age of the study population was 72 years (range: 22-98 years) and 57.4% were female. The median CHA2DS2-VASc and HAS-BLED scores were 4 (range: 0-9) and 1 (range: 0-6), respectively. Vitamin K antagonists and direct oral anticoagulants were used in 15.9% and 79.4% of patients, respectively. The mean time in therapeutic range was 52.9% for patients receiving vitamin K antagonists, and 76% of those patients had an inadequate time in therapeutic range with <70%. The most common prescribed direct oral anticoagulants were rivaroxaban (38.1%), apixaban (25.5%), and edoxaban (11.2%). The rate of overuse of vitamin K antagonists and direct oral anticoagulants was high (76.1%) in patients with low stroke risk, and more than one-fourth of patients on direct oral anticoagulant therapy were receiving a reduced dose of direct oral anticoagulants. Among patients who were on direct oral anticoagulant treatment, patients with apixaban treatment were older, had higher CHA2DS2-VASc and HAS-BLED scores, and had lower creatinine clearance than the patients receiving other direct oral anticoagulants. CONCLUSIONS: The ROTA study provides important real-world information about anticoagulant treatment patterns in patients with atrial fibrillation.time in therapeutic range with <70%.


Subject(s)
Atrial Fibrillation , Embolism , Stroke , Humans , Female , Young Adult , Adult , Middle Aged , Aged , Aged, 80 and over , Male , Anticoagulants , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Prospective Studies , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , Rivaroxaban/therapeutic use , Pyridones/therapeutic use , Embolism/drug therapy , Vitamin K , Administration, Oral , Dabigatran/therapeutic use
5.
Kardiol Pol ; 81(2): 132-140, 2023.
Article in English | MEDLINE | ID: mdl-36594528

ABSTRACT

BACKGROUND: It is unclear whether warfarin treatment with high time in therapeutic range (TTR) is as effective and safe as non-vitamin K antagonist oral anticoagulants (NOACs). It is crucial to compare warfarin with effective TTR and NOACs to predict long-term adverse events in patients with atrial fibrillation. AIMS: We aimed to compare the long-term follow-up results of patients with atrial fibrillation (AF) who use vitamin K antagonists (VKAs) with effective TTR and NOACs. METHODS: A total of 1140 patients were followed at 35 different centers for five years. During the follow-up period, the international normalized ratio (INR) values were studied at least 4 times a year, and the TTR values were calculated according to the Roosendaal method. The effective TTR level was accepted as >60% as recommended by the guidelines. There were 254 patients in the effective TTR group and 886 patients in the NOAC group. Ischemic cerebrovascular disease/transient ischemic attack (CVD/TIA), intracranial bleeding, and mortality were considered primary endpoints based on one-year and five-year follow-ups. RESULTS: Ischemic CVD/TIA (3.9% vs. 6.2%; P = 0.17) and intracranial bleeding (0.4% vs. 0.5%; P = 0.69), the one-year mortality rate (7.1% vs. 8.1%; P = 0.59), the five-year mortality rate (24% vs. 26.3%; P = 0.46) were not different between the effective TTR and NOACs groups during the follow-up, respectively. The CHA2DS2-VASC score was similar between the warfarin with effective TTR group and the NOAC group (3 [2-4] vs. 3 [2-4]; P = 0.17, respectively). Additionally, survival free-time did not differ between the warfarin with effective TTR group and each NOAC in the Kaplan-Meier analysis (dabigatran; P = 0.59, rivaroxaban; P = 0.34, apixaban; P = 0.26, and edoxaban; P = 0.14). CONCLUSION: There was no significant difference in primary outcomes between the effective TTR and NOAC groups in AF patients.


Subject(s)
Atrial Fibrillation , Ischemic Attack, Transient , Stroke , Humans , Administration, Oral , Anticoagulants , Atrial Fibrillation/drug therapy , Dabigatran/therapeutic use , Ischemic Attack, Transient/chemically induced , Ischemic Attack, Transient/drug therapy , Pyridones/therapeutic use , Rivaroxaban/therapeutic use , Stroke/prevention & control , Stroke/drug therapy , Warfarin/therapeutic use , Warfarin/adverse effects
6.
J Clin Pharmacol ; 63(6): 654-663, 2023 06.
Article in English | MEDLINE | ID: mdl-36609916

ABSTRACT

Four direct oral anticoagulants (DOACs) are used in Japan (edoxaban, rivaroxaban, apixaban, and dabigatran); however, few studies have examined the long-term treatment persistence of these DOACs. Furthermore, the factors associated with persistence remain unclear. This single-center, retrospective cohort study enrolled participants who were newly prescribed the 4 DOACs between January 1, 2012, and April 30, 2020. We assessed the treatment persistence rate by calculating the cumulative incidence rate of prescription switch or discontinuation for 5 years from the initial prescription. The factors associated with persistence were examined using multivariate analysis. The edoxaban was used as a reference for comparison with the other DOACs. The persistence rate at 5 years was 52.9% for all DOACs, including 67.0%, 51.6%, 50.2%, and 37.0% for edoxaban, rivaroxaban, apixaban, and dabigatran, respectively. Multivariate analysis revealed that age >65 years (hazard ratio [HR], 0.62 [95%CI, 0.41-0.93]), chronic kidney disease (HR, 1.63 [95%CI, 1.11-2.39]), baseline hemoglobin (HR, 0.85 [95%CI, 0.78-0.93]), diabetes mellitus (HR, 0.51 [95%CI, 0.29-0.93]), and type of DOACs (rivaroxaban: HR, 1.81 [95%CI, 1.03-3.18]; apixaban: HR, 2.00 [95%CI, 1.15-3.48]; and dabigatran: HR, 2.84 [95%CI, 1.66-4.86]) were significantly associated with nonpersistence at 1 year. At 5 years, diabetes mellitus (HR, 0.60 [95%CI, 0.37-0.97]) and type of DOAC were significantly associated with nonpersistence (rivaroxaban: HR, 1.79 [95%CI, 1.09-2.94]; apixaban: HR, 2.04 [95%CI, 1.26-3.31]; and dabigatran: HR, 2.76 [1.73-4.42]). Long-term treatment persistence differed according to the type of DOAC, with edoxaban exhibiting the highest level of persistence. The factors associated with persistence may change over the treatment course, but larger studies are required to generalize our findings.


Subject(s)
Atrial Fibrillation , Stroke , Humans , Aged , Atrial Fibrillation/drug therapy , Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Rivaroxaban/therapeutic use , Dabigatran/therapeutic use , Anticoagulants/therapeutic use , Retrospective Studies , Pyridones/therapeutic use , Administration, Oral
7.
Ann Pharmacother ; 57(8): 918-924, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36373362

ABSTRACT

BACKGROUND: Warfarin, a commonly prescribed anticoagulant, requires frequent lab monitoring. Lab monitoring puts patients at risk of COVID-19 exposure and diverts medical resources away from health care systems. Direct oral anticoagulants (DOACs) do not require routine therapeutic monitoring and are indicated first line for nonvalvular atrial fibrillation (NVAF) stroke prevention and venous thromboembolism (VTE) prevention/treatment. OBJECTIVE: The purpose of the study was to determine the proportion of patients who qualify for DOACs and assess for predictors of qualification. METHODS: This cross-sectional study investigated patients on warfarin managed by Michigan Medicine Anticoagulation Service. Direct oral anticoagulant eligibility criteria were established using apixaban, dabigatran, and rivaroxaban package inserts. Patient eligibility was determined through chart review. The primary outcome was the proportion of patients who qualify for DOACs based on clinical factors. Predictors of DOAC qualification were assessed. RESULTS: This study included 3205 patients and found 51.8% (n = 1661) of patients qualified for DOACs. Qualifying patients were older (71.9 vs 59.4 years, P < 0.0001) with a higher CHA2DS2 VASc (3.7 vs 3.4, P < 0.0007). The primary disqualifying factor was extreme weight, high and low. Accounting for a patient's sex and referral source, age > 65 (odds ratio [OR] = 1.9, P < 0.0001) and NVAF indication (OR = 5.6, P < 0.0001) were significant predictors for DOAC qualification. CONCLUSION AND RELEVANCE: Approximately 52% of patients on warfarin were eligible for DOACs. This presents an opportunity to reduce patient exposure to health care settings and health care utilization in the setting of COVID-19. Increased costs of DOACs need to be assessed.


Subject(s)
Atrial Fibrillation , COVID-19 , Stroke , Humans , Warfarin/adverse effects , Stroke/prevention & control , Cross-Sectional Studies , Anticoagulants , Rivaroxaban/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Dabigatran/therapeutic use , Pyridones/therapeutic use , Administration, Oral , Retrospective Studies
8.
Cardiovasc Drugs Ther ; 37(2): 363-377, 2023 04.
Article in English | MEDLINE | ID: mdl-34436708

ABSTRACT

PURPOSE: We aimed to determine the safety of direct oral anticoagulants (DOACs) for stroke prevention and treatment in patients with atrial fibrillation (AF). METHODS: A systematic search of four databases (PubMed, EMBASE, Web of Science, and Cochrane Library) was performed to identify randomized controlled trials (RCTs) reporting severe bleeding events in patients taking DOACs or vitamin K antagonists (VKAs). In this frequency-based network meta-analysis, odds ratios and 95% confidence intervals were used for reporting. Based on the surface under the cumulative ranking curves (SUCRA), the relative ranking probability of each group was generated. RESULTS: Twenty-three RCTs met the inclusion criteria, and a total of 87,616 patients were enrolled. The bleeding safety of DOACs for stroke prevention and treatment in patients with AF was ranked from highest to lowest as follows: fatal bleeding: edoxaban (SUCRA,80.2), rivaroxaban (SUCRA,68.3), apixaban (SUCRA,48.5), dabigatran (SUCRA,40.0), VKAs (SUCRA,12.9); major bleeding: dabigatran (SUCRA,74.0), apixaban (SUCRA,71.5), edoxaban (SUCRA,66.5), rivaroxaban (SUCRA,22.7), VKAs (SUCRA,15.4); gastrointestinal bleeding: apixaban (SUCRA,55.9), VKAs (SUCRA,53.7), edoxaban (SUCRA,50.5), rivaroxaban (SUCRA,50.4), dabigatran (SUCRA,39.5); intracranial hemorrhage: dabigatran (SUCRA,84.6), edoxaban (SUCRA,74.1), apixaban (SUCRA,65.8), rivaroxaban (SUCRA,24.4), VKAs (SUCRA,1.1). CONCLUSION: Based on current evidence, for stroke prevention and treatment in patients with AF, the most safe DOAC is edoxaban in terms of fatal bleeding; dabigatran in terms of major bleeding and intracranial hemorrhage and apixaban in terms of gastrointestinal bleeding. However, given the nature of indirect comparisons, more high-quality evidence from head-to-head comparisons is still needed to confirm them.


Subject(s)
Anticoagulants , Atrial Fibrillation , Stroke , Vitamin K , Humans , Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Dabigatran/adverse effects , Dabigatran/therapeutic use , Gastrointestinal Hemorrhage/chemically induced , Intracranial Hemorrhages/chemically induced , Network Meta-Analysis , Rivaroxaban/adverse effects , Rivaroxaban/therapeutic use , Stroke/chemically induced , Stroke/etiology , Stroke/prevention & control , Vitamin K/antagonists & inhibitors , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/therapeutic use , Administration, Oral
9.
NEJM Evid ; 2(7): EVIDe2300106, 2023 Jul.
Article in English | MEDLINE | ID: mdl-38320170

ABSTRACT

Direct oral anticoagulants such as apixaban or dabigatran have revolutionized anticoagulant treatment. These drugs, which specifically inhibit either factor Xa or thrombin, respectively, are at least as effective as vitamin K antagonists (e.g., warfarin) in patients with atrial fibrillation or venous thromboembolism and have important safety advantages that include reduced risks of intracranial hemorrhage, fatal bleeding, and all-cause mortality.1-3 They are also much easier to use because they are given in a fixed dose without routine laboratory monitoring of the anticoagulant effect and dose adjustment in the individual patient.


Subject(s)
Anticoagulants , Rivaroxaban , Humans , Rivaroxaban/therapeutic use , Anticoagulants/therapeutic use , Warfarin/therapeutic use , Dabigatran/therapeutic use , Heart Valves
12.
Int J Clin Pract ; 2022: 6707985, 2022.
Article in English | MEDLINE | ID: mdl-35685531

ABSTRACT

Background: Data directly comparing trends in the use of different oral anticoagulants (OACs) among patients with atrial fibrillation (AF) from different countries are limited. We addressed this using a large-scale network cohort study in the United States (US), Belgium, France, Germany, and the United Kingdom (UK). Methods: We used nine databases (claims or electronic health records) that had been converted into the Observational Medical Outcomes Partnership Common Data Model with analysis performed using open-source analytical tools. We identified adults with AF and a first OAC prescription, either vitamin K antagonist (VKA) or direct oral anticoagulant (DOAC), from 2010 to 2017. We described time trends in use, continuation, and switching. Results: In 2010, 87.5%-99.8% of patients started on a VKA. By 2017, the majority started on a DOAC: 87.0% (US), 88.3% (Belgium), 93.1% (France), 88.4% (Germany), and 86.1%-86.7% (UK). In the UK, DOACs became the most common starting OAC in 2015, 2-3 years later than elsewhere. Apixaban was the most common starting OAC by 2017, 50.2%-57.8% (US), 31.4% (Belgium), 45.9% (France), 39.5% (Germany), and 49.8%-50.5% (UK), followed by rivaroxaban, 24.8%-32.5% (US), 25.7% (Belgium), 38.4% (France), 24.9% (Germany), and 30.2%-31.2% (UK). Long-term treatment was less common in the US than in Europe, especially the UK. A minority of patients switched from their index OAC in the short and long term. Conclusions: From 2010 to 2017, VKA use had significantly declined and DOAC use had significantly increased in the US and Europe. Apixaban was the most prescribed OAC in 2017, followed by rivaroxaban.


Subject(s)
Atrial Fibrillation , Stroke , Administration, Oral , Adult , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Cohort Studies , Dabigatran/therapeutic use , France , Humans , Rivaroxaban/therapeutic use , Stroke/drug therapy , United States/epidemiology
13.
Lancet Child Adolesc Health ; 6(3): 207-214, 2022 03.
Article in English | MEDLINE | ID: mdl-35033222

ABSTRACT

With the increasing incidence of thromboembolism in children and improvement in management for patients with medically complex diseases, expanded availability of safe and effective anticoagulant medications is needed. Traditionally, the most common anticoagulants used for the treatment or prevention of venous thromboembolism or embolic stroke in children were either unfractionated heparin or the low-molecular-weight heparins. These medications require either intravenous access or daily subcutaneous injections, in addition to multiple venepunctures to monitor drug concentrations. Direct oral anticoagulants provide an alternative, and potentially safer, choice for children, as they are available in oral formulations and do not require drug monitoring. With the approval of the direct factor Xa inhibitor, rivaroxaban (by the European Medicines Agency and Health Canada), and the direct thrombin inhibitor, dabigatran (by the European Medicines Agency and US Food and Drug Administration), the field of paediatric anticoagulation is changing. In this Review, we provide an overview of the four direct oral anticoagulants approved in adults for the treatment and prevention of thrombosis and the completed and ongoing paediatric trials.


Subject(s)
Clinical Trials as Topic , Dabigatran/therapeutic use , Factor Xa Inhibitors/therapeutic use , Pediatrics , Pyrazoles/therapeutic use , Pyridines/therapeutic use , Pyridones/therapeutic use , Rivaroxaban/therapeutic use , Thiazoles/therapeutic use , Antithrombins/therapeutic use , Child , Humans
16.
J Eval Clin Pract ; 28(3): 436-444, 2022 06.
Article in English | MEDLINE | ID: mdl-34636130

ABSTRACT

BACKGROUND: In the treatment of atrial fibrillation (AF), anticoagulant medications such as warfarin and rivaroxaban are commonly prescribed to reduce the risk of ischaemic strokes, and other thromboembolic events. Research has highlighted advantages and disadvantages of each of these medications, but there remains an absence of qualitative evidence regarding the lived experiences of AF patients. The present study helps address this gap and obtain a greater understanding of the patient experience and beliefs surrounding their anticoagulant medication. METHOD: Semi-structured qualitative interviews with a purposive sample of 20 participants (10 warfarin, 10 rivaroxaban). Interviews were transcribed verbatim and thematically analysed. RESULTS: Data analysis led to the generation of three key themes: positive perceptions of medication, distrust of alternatives, and inconsistencies in support experiences. CONCLUSIONS: Positive perceptions of one anticoagulant medication (ACM) and distrust of alternatives may influence patients' confidence in switching medications. This is potentially problematic where there is a lack of patient engagement in medication changes, as seen during the COVID pandemic. Gaps in patient understanding of anticoagulation, including lack of clarity around medications selection and misconceptions about treatment, were evident. By addressing these misconceptions, clinicians may be better positioned to support people with AF in self-management of their ACM.


Subject(s)
Atrial Fibrillation , COVID-19 , Stroke , Administration, Oral , Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Dabigatran/therapeutic use , Humans , Rivaroxaban/therapeutic use , Trust , Warfarin/therapeutic use
17.
J Clin Pharm Ther ; 47(4): 523-530, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34783090

ABSTRACT

WHAT IS KNOWN AND OBJECTIVE: With the high cost, the long-term persistence of new oral anticoagulants (NOACs) was lower than that of warfarin in Chinese patients with non-valvular atrial fibrillation (NVAF) for a long time. The prices of NOACs (apixaban, rivaroxaban and dabigatran) decreased significantly over the past year in mainland China. The objective of this study was to evaluate the cost-effectiveness of NOACs versus warfarin for preventing stroke in patients with NVAF from a Chinese healthcare system perspective. METHODS: A decision tree and Markov model were used to assess the treatment strategies of four NOACs versus warfarin over a lifetime horizon. For each treatment strategy, the total lifetime cost, quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) were calculated. The impact of parameter uncertainties on base-case analysis results was evaluated using sensitivity analyses. RESULTS AND DISCUSSION: In the base-case analysis, compared with warfarin, apixaban had a decreased total lifetime cost of USD 389 and rivaroxaban of USD 1482, while low-dose dabigatran had an increased total lifetime cost of USD 925 and high-dose dabigatran of USD 6641, with QALY increasing by 0.53, 1.32, 0.92 and 1.83, respectively. The ICER of low-dose dabigatran versus warfarin was USD 1005 per QALY gain, while those of apixaban (-USD 734 per QALY gain) and rivaroxaban (-USD 1123 per QALY gain) were negative. One-way and probabilistic sensitivity analyses indicated that the base-case results were robust by applying certain varying parameters to the model. WHAT IS NEW AND CONCLUSION: These four NOAC (apixaban, rivaroxaban, low-dose dabigatran and high-dose dabigatran) treatment strategies were cost-effective compared with warfarin and recommended as substitutes for warfarin treatment for preventing stroke in patients with NVAF in the healthcare system of China, which might be driven by large drug price reductions in the past year.


Subject(s)
Atrial Fibrillation , Stroke , Administration, Oral , Anticoagulants/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Cost-Benefit Analysis , Dabigatran/therapeutic use , Humans , Pyridones/therapeutic use , Rivaroxaban/therapeutic use , Stroke/drug therapy , Stroke/etiology , Stroke/prevention & control , Warfarin/therapeutic use
19.
PLoS One ; 16(11): e0260585, 2021.
Article in English | MEDLINE | ID: mdl-34843582

ABSTRACT

Several direct oral anticoagulants have been developed to prevent cardiogenic thrombosis in patients with atrial fibrillation, on the other hand, have the complication of bleeding. Since clinical course after bleeding with direct oral anticoagulant remains unclear, the present retrospective cohort study was to clarify the course after hemorrhage among patients receiving direct oral anticoagulants. Among all 2005 patients prescribed dabigatran, rivaroxaban, apixaban, or edoxaban between April 2011 and June 2017, subjects comprised 96 patients with non-valvular atrial fibrillation who experienced relevant bleeding during direct oral anticoagulant therapy (Bleeding Academic Research Consortium type 2 or above). The clinical course after hemorrhage was reviewed to examine whether rebleeding or thrombotic events occurred up to the end of December 2019. Gastrointestinal bleeding was the most frequent cause of initial bleeding (57 patients, 59%). Rebleeding occurred in 11 patients (4.5%/year), with gastrointestinal bleeding in 10 and subarachnoid hemorrhage in 1. All rebleeding occurred in patients who resumed anticoagulation therapy. Another significant factor related with rebleeding included past history of gastrointestinal bleeding. On the other hand, major adverse cardiac and cerebrovascular events occurred in 6 patients older than 75 years old or more (2.5%/year), with systemic thrombosis in 4 and cardiac death in 2. All 4 patients with systemic thrombosis withheld anticoagulants after index bleeding, although only 10 patients withheld anticoagulation therapy. Rebleeding should be taken care of when anticoagulants are resumed after bleeding, particularly among patients who initially experienced gastrointestinal bleeding. Systemic thrombosis occurred at a high rate when anticoagulant therapy was withheld after bleeding.


Subject(s)
Atrial Fibrillation/drug therapy , Factor Xa Inhibitors/therapeutic use , Hemorrhage/chemically induced , Thrombosis/drug therapy , Aged , Aged, 80 and over , Atrial Fibrillation/complications , Dabigatran/adverse effects , Dabigatran/therapeutic use , Factor Xa Inhibitors/adverse effects , Female , Gastrointestinal Hemorrhage/chemically induced , Humans , Male , Pyrazoles/adverse effects , Pyrazoles/therapeutic use , Pyridines/adverse effects , Pyridines/therapeutic use , Pyridones/adverse effects , Pyridones/therapeutic use , Retrospective Studies , Rivaroxaban/adverse effects , Rivaroxaban/therapeutic use , Thiazoles/adverse effects , Thiazoles/therapeutic use , Thrombosis/complications
20.
PLoS One ; 16(11): e0259199, 2021.
Article in English | MEDLINE | ID: mdl-34762667

ABSTRACT

BACKGROUND: The incidence of atrial fibrillation (AF) is increasing, and effective anticoagulation therapy can prevent adverse events. Selecting the appropriate OAC based on patient characteristics has become a challenge. Interventions are going to be a potential area of focus. OBJECTIVES: To explore the discrepancies between clinician prescriptions and recommended guidelines of oral anticoagulants (OACs) for patients with atrial fibrillation (AF), and to provide direction for improving anticoagulation strategies for treating patients with AF. MATERIALS AND METHODS: Data were collected from the electronic medical record system of Fuwai Yunnan Cardiovascular Hospital between July 2019 and January 2020. The suitability of prescribed OACs for patients with AF was assessed according to the Rules for Avoiding Prescription Inappropriateness, the prescribed medicine label, and any relevant antithrombotic guidelines for treating patients with AF. RESULTS: A total of 460 patients met the inclusion criteria. Of these, 53.7% received an appropriate prescription and 46.3% received an inappropriate prescription. Of the patients who received inappropriate prescriptions, 15.4% were prescribed without the presenting appropriate indicators, 1.3% were prescribed inappropriate drug selection, and 29.6% were prescribed inappropriate drug doses. For patients prescribed without providing appropriate indicators, 2.2% had no indication for medication and 13.3% had an indication for medication, but not a specific OAC. For patients with inappropriate drug selection, 1, 5 patients were on rivaroxaban, dabigatran respectively. The distribution of NOAC doses was as follows: dabigatran standard dose (45.2%), the low dose (54.8%). Rivaroxaban standard dose (58.9%), low dose (36.8%), high dose (4.3%). A total of 44 patients (9.6%) experienced bleeding events, 12 patients (2.6%) experienced embolic events, and 7 patients experienced other adverse events after dosing. CONCLUSIONS: In clinical practice, it is common for patients with AF to receive inappropriate prescriptions of OACs. Therefore there is a need to enhance anticoagulation management in patients with AF to improve the appropriate use of OACs.


Subject(s)
Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Inappropriate Prescribing/statistics & numerical data , Administration, Oral , Aged , Anticoagulants/adverse effects , China , Dabigatran/adverse effects , Dabigatran/therapeutic use , Female , Hemorrhage/etiology , Hospitals , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Rivaroxaban/adverse effects , Rivaroxaban/therapeutic use
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