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Journal of Thrombosis and Thrombolysis Jan 2023Data on non-vitamin K antagonist oral anticoagulants (NOACs) in transcatheter aortic valve replacement (TAVR) patients are controversial. In patients without atrial...
Data on non-vitamin K antagonist oral anticoagulants (NOACs) in transcatheter aortic valve replacement (TAVR) patients are controversial. In patients without atrial fibrillation (AF), rivaroxaban showed enhanced ischemia and bleeding as compared to standard of care. ENVISAGE showed enhanced bleeding in AF patients as compared to vitamin K antagonist (VKA). Only apixaban was non-inferior but failed superiority regarding bleeding in AF patients after TAVR. One could hypothesize that this might be due to pharmacokinetics of NOACs. Therefore, we compared outcome in rivaroxaban/edoxaban (once-daily) and apixaban (twice-daily) treated patients. 568 patients with indication for permanent oral anticoagulation due to AF undergoing TAVR were analyzed via inverse probability of treatment weighting. Valve academic research consortium complications during 30-day follow-up were assessed. Bleeding complications were similar in once-daily and twice-daily NOACs (major: 22 (7.5%) vs. 14 (5.3%), p = 0.285; minor: 66 (22.4%) vs. 46 (17.4%), p = 0.133). Complications did not change when splitting the cohort in the different agents apixaban, rivaroxaban and edoxaban. These findings remained robust after multivariate analysis. In summary, twice-daily and once-daily NOACs did not differ regarding bleeding complications in a hypothesis generating real-world cohort of TAVR patients with AF.
Topics: Humans; Anticoagulants; Rivaroxaban; Transcatheter Aortic Valve Replacement; Administration, Oral; Hemorrhage; Atrial Fibrillation; Fibrinolytic Agents; Stroke; Treatment Outcome
PubMed: 36318378
DOI: 10.1007/s11239-022-02721-6 -
JAMA Network Open Aug 2023Extending the duration of oral anticoagulation for venous thromboembolism (VTE) beyond the initial 3 to 6 months of treatment is often recommended, but it is not clear...
IMPORTANCE
Extending the duration of oral anticoagulation for venous thromboembolism (VTE) beyond the initial 3 to 6 months of treatment is often recommended, but it is not clear whether clinical outcomes differ when using direct oral anticoagulants (DOACs) or warfarin.
OBJECTIVE
To compare rates of recurrent VTE, hospitalizations for hemorrhage, and all-cause death among adults prescribed DOACs or warfarin whose anticoagulant treatment was extended beyond 6 months after acute VTE.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study was conducted in 2 integrated health care delivery systems in California with adults aged 18 years or older who received a diagnosis of incident VTE between 2010 and 2018 and completed at least 6 months of oral anticoagulant treatment with DOACs or warfarin. Patients were followed from the end of the initial 6-month treatment period until discontinuation of anticoagulation, occurrence of an outcome event, health plan disenrollment, or end of the study follow-up period (December 31, 2019). Data were obtained from the Kaiser Permanente Virtual Data Warehouse and electronic health records. Data analysis was conducted from March 2022 to January 2023.
EXPOSURE
Dispensed prescriptions of DOACs or warfarin after a 6-month initial treatment for VTE.
MAIN OUTCOMES AND MEASURES
The primary outcomes were rates per 100 person-years of recurrent VTE, hospitalizations for hemorrhage, and all-cause death. Comparison of DOAC and warfarin outcomes were performed using multivariable Cox proportional hazards regression.
RESULTS
A total of 18 495 patients (5477 [29.6%] aged ≥75 years; 8973 women [48.5%]) with VTE who were treated with at least 6 months of anticoagulation were identified, of whom 2134 (11.5%) were receiving DOAC therapy and 16 361 (88.5%) were receiving warfarin therapy. Unadjusted event rates were lower for patients receiving DOAC therapy than warfarin therapy for recurrent VTE (event rate per 100 person-years, 2.92 [95% CI, 2.29-3.54] vs 4.14 [95% CI, 3.90-4.38]), hospitalizations for hemorrhage (event rate per 100 person-years, 1.02 [95% CI, 0.66-1.39] vs 1.81 [95% CI, 1.66-1.97]), and all-cause death (event rate per 100 person-years, 3.79 [95% CI, 3.09-4.49] vs 5.40 [95% CI, 5.13-5.66]). After multivariable adjustment, DOAC treatment was associated with a lower risk of recurrent VTE (adjusted hazard ratio [aHR], 0.66; 95% CI, 0.52-0.82). For patients prescribed DOAC treatment, the risks of hospitalization for hemorrhage (aHR, 0.79; 95% CI, 0.54-1.17) and all-cause death (aHR, 0.96; 95% CI, 0.78-1.19) were not significantly different than those for patients prescribed warfarin treatment.
CONCLUSIONS AND RELEVANCE
In this cohort study of patients with VTE who continued warfarin or DOAC anticoagulation beyond 6 months, DOAC treatment was associated with a lower risk of recurrent VTE, supporting the use of DOACs for the extended treatment of VTE in terms of clinical outcomes.
Topics: Adult; Humans; Female; Warfarin; Venous Thromboembolism; Cohort Studies; Anticoagulants; Hemorrhage
PubMed: 37581888
DOI: 10.1001/jamanetworkopen.2023.28033 -
Revista Da Associacao Medica Brasileira... 2023The aim of this study was to carry out a systematic review of the literature with meta-analysis to evaluate the effect of using oral contraceptive and hormone... (Meta-Analysis)
Meta-Analysis
Does the use of oral contraceptives or hormone replacement therapy offer protection against the formation or rupture of intracranial aneurysms in women?: a systematic review and meta-analysis.
OBJECTIVE
The aim of this study was to carry out a systematic review of the literature with meta-analysis to evaluate the effect of using oral contraceptive and hormone replacement therapy as a protective factor in the formation of intracranial aneurysms and subarachnoid hemorrhage.
METHODS
This is a systematic review of the literature with meta-analysis, using PubMed and Embase as databases and the PRISMA method. Case-control and cohort studies published until December 2022 were included in this review.
RESULTS
Four studies were included in this review; three of which were eligible for meta-analysis. Regarding the use of oral contraceptive and the development of subarachnoid hemorrhage, there was a lower risk of aneurysm rupture with an odds ratio 0.65 (confidence interval 0.5-0.85). In the analysis of patients using hormone replacement therapy and developing subarachnoid hemorrhage, there was also a lower risk of aneurysm rupture with an OR 0.54 (CI 0.39-0.74). Only one article analyzed the formation of intracranial aneurysm and the use of hormone replacement therapy and oral contraceptive, and there was a protective effect with the use of these medications. oral contraceptive: OR 2.1 (CI 1.2-3.8) and hormone replacement therapy: OR 3.1 (CI 1.5-6.2).
CONCLUSION
The use of hormone replacement therapy and oral contraceptive has a protective effect in intracranial aneurysm rupture and formation.
Topics: Humans; Female; Intracranial Aneurysm; Contraceptives, Oral; Subarachnoid Hemorrhage; Hormone Replacement Therapy; Cohort Studies; Risk Factors
PubMed: 37556637
DOI: 10.1590/1806-9282.2023S118 -
Science Progress 2021All cancers can increase the risk of developing venous thromboembolism (VTE), and anticoagulants should be considered as an optimal treatment for patients suffering from... (Meta-Analysis)
Meta-Analysis
All cancers can increase the risk of developing venous thromboembolism (VTE), and anticoagulants should be considered as an optimal treatment for patients suffering from cancer-associated VTE. However, there is still a debate about whether the new oral anticoagulant, rivaroxaban, can bring better efficacy and safety outcomes globally. Thus, this systematic review and meta-analysis was conducted to evaluate the efficacy and safety of rivaroxaban. We searched PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and China National Knowledge Infrastructure for relevant published papers before 1 September 2019, with no language restrictions. The primary outcomes are defined as the recurrence of VTE. The secondary outcomes are defined as clinically relevant non-major bleeding, adverse major bleeding events, and all-cause of death. The data were analyzed by Stata with risk ratio (RR) and 95% confidence interval (CI). Four trials encompassing 1996 patients were included. Rivaroxaban reduced recurrent VTE with no significant difference (RR = 0.68, 95% CI = 0.43-1.07). Similarly, there were no significant differences in adverse major bleeding events (RR = 0.86, 95% CI = 0.37-2.00), clinically relevant non-major bleeding (RR = 1.24, 95% CI = 0.73-2.12) and all-cause mortality (RR = 0.76, 95% CI = 0.40-1.44). In a selected study population of cancer patients with VTE, rivaroxaban is as good as other anticoagulants. Further, carefully designed randomized controlled trials should be performed to confirm these results.
Topics: Administration, Oral; Anticoagulants; Hemorrhage; Humans; Neoplasms; Rivaroxaban; Venous Thromboembolism
PubMed: 33913387
DOI: 10.1177/00368504211012160 -
Hematology. American Society of... Dec 2020Women with bleeding disorders suffer from multiple bleeding symptoms, including easy bruising, epistaxis, bleeding from minor wounds and the oral cavity, and bleeding... (Review)
Review
Women with bleeding disorders suffer from multiple bleeding symptoms, including easy bruising, epistaxis, bleeding from minor wounds and the oral cavity, and bleeding after dental work or surgery. However, women with bleeding disorders especially suffer from gynecologic and obstetrical bleeding. These symptoms often are not recognized as abnormal, and many women are left undiagnosed and without access to appropriate medical care. Additional challenges to diagnosing women with bleeding disorders include lack of access to appropriate laboratory testing and issues around disease classification and nomenclature. Efforts have been undertaken to address these challenges, including the development and validation of bleeding assessment tools and strategies to clarify diagnostic thresholds and algorithms for von Willebrand disease (VWD) and platelet function disorders. Efforts to improve communication with the nomenclature used for hemophilia carriers are also underway.
Topics: Adolescent; Algorithms; Female; Health Services Accessibility; Hemorrhage; Humans; Women's Health Services; von Willebrand Diseases
PubMed: 33275722
DOI: 10.1182/hematology.2020000140 -
Acta Medica Portuguesa May 2022Dabigatran is a direct oral anticoagulant used to prevent stroke and systemic embolism in patients with atrial fibrillation. In situations that require the urgent...
Dabigatran is a direct oral anticoagulant used to prevent stroke and systemic embolism in patients with atrial fibrillation. In situations that require the urgent reversal of its anticoagulant activity, such as in the case of severe bleeding that is life-threatening; urgent/ emergent surgery or invasive procedures with significant bleeding risk; and the need for thrombolysis in a patient with ischemic stroke, several measures can be taken, including the use of its specific reversal agent, idarucizumab. Based on the guidelines for the use of reversal agents for oral anticoagulants, and on the clinical experience of reversal of dabigatran, a practical guide is presented for use in clinical situations where reversal of dabigatran anticoagulation is required, including the use of idarucizumab. The adoption of this type of guideline contributes to therapeutic optimization and, consequently, greater reversal efficiency and a better resource management.
Topics: Humans; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage
PubMed: 36279894
DOI: 10.20344/amp.17662 -
Annals of Emergency Medicine Sep 2023Direct oral anticoagulants (DOACs) are widely used for the prevention and treatment of venous thromboembolism and stroke. When emergency reversal of DOAC-related... (Review)
Review
Direct oral anticoagulants (DOACs) are widely used for the prevention and treatment of venous thromboembolism and stroke. When emergency reversal of DOAC-related anticoagulation is required, specific DOAC reversal agents are recommended, including idarucizumab for dabigatran reversal and andexanet alfa for apixaban and rivaroxaban reversal. However, specific reversal agents are not always available, andexanet alfa has not been approved for urgent surgery, and clinicians need to know the patient's anticoagulant medication before administering these treatments. Four-factor prothrombin complex concentrates (4F-PCCs) are recognized as nonspecific, alternative hemostatic agents for treatment of DOAC-related bleeding. Evidence from preclinical and clinical studies shows that they may reduce the anticoagulant effects of DOACs and may help control DOAC-related bleeding. However, randomized controlled trials are lacking, and most data are from retrospective or single-arm prospective studies in bleeding associated with activated factor X inhibitors. There are no clinical data showing the efficacy of 4F-PCC for the treatment of bleeding in dabigatran-treated patients. This review focuses on the current evidence of 4F-PCC use in controlling bleeding associated with DOACs and provides an expert opinion on the relevance of these data for clinical practice. The current treatment landscape, unmet needs, and future directions are also discussed.
Topics: Humans; Dabigatran; Clinical Relevance; Retrospective Studies; Prospective Studies; Anticoagulants; Hemorrhage; Administration, Oral; Recombinant Proteins
PubMed: 37204347
DOI: 10.1016/j.annemergmed.2023.04.015 -
International Journal of Stroke :... Oct 2023Elderly patients with nonvalvular atrial fibrillation (NVAF) might have a higher risk of intracerebral hemorrhage. To investigate this, we compared the incidence of...
Risk of both intracranial hemorrhage and ischemic stroke in elderly individuals with nonvalvular atrial fibrillation taking direct oral anticoagulants compared with warfarin: Analysis of the ANAFIE registry.
BACKGROUND AND AIMS
Elderly patients with nonvalvular atrial fibrillation (NVAF) might have a higher risk of intracerebral hemorrhage. To investigate this, we compared the incidence of intracranial hemorrhage (ICH) and its subtypes, as well as ischemic stroke, in patients taking direct oral anticoagulants (DOACs) compared with warfarin in a real-world setting. We also determined the baseline characteristics associated with both ICH and ischemic stroke.
METHODS
Patients aged ⩾ 75 years with documented NVAF enrolled in the prospective, multicenter, observational All Nippon Atrial Fibrillation in the Elderly Registry between October 2016 and January 2018 were evaluated. The co-primary endpoints were the incidence of ischemic stroke and ICH. Secondary endpoints included subtypes of ICH.
RESULTS
Of 32,275 patients (13,793 women; median age, 81.0 years) analyzed, 21,585 (66.9%) were taking DOACs and 8233 (25.5%) were taking warfarin. During the median 1.88-year follow-up, 743 patients (1.24/100 person-years) developed ischemic stroke and 453 (0.75/100 person-years) developed ICH (intracerebral hemorrhage, 189; subarachnoid hemorrhage, 72; subdural/epidural hemorrhage, 190; unknown subtype, 2). The incidence of ischemic stroke (adjusted hazard ratio (aHR) 0.82, 95% confidence interval (CI) 0.70-0.97), ICH (aHR 0.68, 95% CI 0.55-0.83), and subdural/epidural hemorrhage (aHR 0.53, 95% CI 0.39-0.72) was lower in DOAC users versus warfarin users. The incidence of fatal ICH and fatal subarachnoid hemorrhage was also lower in DOAC users versus warfarin users. Several baseline characteristics other than anticoagulants were also associated with the incidence of the endpoints. Of these, history of cerebrovascular disease (aHR 2.39, 95% CI 2.05-2.78), persistent NVAF, (aHR 1.90, 95% CI 1.53-2.36), and long-standing persistent/permanent NVAF (aHR 1.92, 95% CI 1.60-2.30) was strongly associated with ischemic stroke; severe hepatic disease (aHR 2.67, 95% CI 1.46-4.88) was strongly associated with overall ICH; and history of fall within 1 year was strongly associated with both overall ICH (aHR 2.29, 95% CI 1.76-2.97) and subdural/epidural hemorrhage (aHR 2.90, 95% CI 1.99-4.23).
CONCLUSION
Patients aged ⩾ 75 years with NVAF taking DOACs had lower risks of ischemic stroke, ICH, and subdural/epidural hemorrhage than those taking warfarin. Fall was strongly associated with the risks of intracranial and subdural/epidural hemorrhage.
DATA ACCESS STATEMENT
The individual de-identified participant data and study protocol will be shared for up to 36 months after the publication of the article. Access criteria for data sharing (including requests) will be decided on by a committee led by Daiichi Sankyo. To gain access, those requesting data access will need to sign a data access agreement. Requests should be directed to [email protected].
Topics: Aged; Humans; Female; Aged, 80 and over; Warfarin; Atrial Fibrillation; Stroke; Ischemic Stroke; Prospective Studies; Subarachnoid Hemorrhage; Treatment Outcome; Anticoagulants; Intracranial Hemorrhages; Cerebral Hemorrhage; Registries; Administration, Oral
PubMed: 37154598
DOI: 10.1177/17474930231175807 -
Cells Jun 2021Glioblastoma is among the tumor entities with an extreme thrombogenic potential and patients are at very high risk of developing a venous thromboembolism (VTE) over the... (Review)
Review
Glioblastoma is among the tumor entities with an extreme thrombogenic potential and patients are at very high risk of developing a venous thromboembolism (VTE) over the course of the disease, with an incidence of up to 30% per year. Major efforts are currently being made to understand and gain novel insights into the underlying pathomechanisms of the development of VTE in patients with glioblastoma and to find appropriate biomarkers. Yet, patients with glioblastoma not only face a high thromboembolic risk but are also at risk of bleeding events. In the case of VTE, a therapeutic anticoagulation with low molecular weight heparin or, in the case of low bleeding risk, treatment with a direct oral anticoagulant, is recommended, according to recently published guidelines. With respect to an elevated bleeding risk in glioblastoma patients, therapeutic anticoagulation remains challenging in this patient group and prospective data for this vulnerable patient group are scarce, particularly with regard to direct oral anticoagulants.
Topics: Biomarkers, Tumor; Glioblastoma; Hemorrhage; Heparin, Low-Molecular-Weight; Humans; Practice Guidelines as Topic; Venous Thromboembolism
PubMed: 34200229
DOI: 10.3390/cells10061414 -
International Journal of Molecular... Dec 2020Nintedanib is a synthetic orally active tyrosine kinase inhibitor, whose main action is to inhibit the receptors of the platelet-derived growth factor, fibroblast growth... (Review)
Review
Nintedanib is a synthetic orally active tyrosine kinase inhibitor, whose main action is to inhibit the receptors of the platelet-derived growth factor, fibroblast growth factor and vascular endothelial growth factor families. The drug also affects other kinases, including Src, Flt-3, LCK, LYN. Nintedanib is used in the treatment of idiopathic pulmonary fibrosis, chronic fibrosing interstitial lung diseases and lung cancer. The mechanism of action suggests that nintedanib should be considered one of the potential agents for inhibiting and revising the fibrosis process related to COVID-19 infections. Due to the known induction of coagulation pathways during COVID-19 infections, possible interaction between nintedanib and anticoagulant seems to be an extremely important issue. In theory, nintedanib could increase the bleeding risk, thrombosis and lead to thrombocytopenia. The data from clinical trials on the concomitant use of nintedanib and antithrombotic agents is very limited as this patient group was within the standard exclusion criteria. Nintedanib is an important therapeutic option, despite its interaction with anticoagulants. If anticoagulant therapy is necessary, the more effective and safer option is the concomitant administration of DOACs and nintedanib, especially when drug-monitored therapy will be used in patients at high risk of bleeding complications.
Topics: Anticoagulants; Antidotes; Antineoplastic Agents; Blood Coagulation Disorders; COVID-19; Drug Interactions; Hemorrhage; Humans; Idiopathic Pulmonary Fibrosis; Indoles; Lung Neoplasms; Protein Kinase Inhibitors; Risk Factors; COVID-19 Drug Treatment
PubMed: 33396592
DOI: 10.3390/ijms22010282