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European Journal of Internal Medicine Mar 2024In a large nationwide administrative database including ∼35 % of Italian population, we analyzed the impact of oral anticoagulant treatment (OAT) in patients with a...
INTRODUCTION
In a large nationwide administrative database including ∼35 % of Italian population, we analyzed the impact of oral anticoagulant treatment (OAT) in patients with a hospital diagnosis of non-valvular atrial fibrillation (NVAF).
METHODS AND RESULTS
Of 170404 OAT-naïve patients (mean age 78.7 years; 49.4 % women), only 61.1 % were prescribed direct oral anticoagulants, DOACs, or vitamin-K antagonists, VKAs; 14.2 % were given aspirin (ASA), and 24.8 % no anti-thrombotic drugs (No Tx). We compared ischemic stroke (IS), IS and systemic embolism (IS/SE), intracranial hemorrhage (ICH), major bleeding (MB), major gastro-intestinal bleeding, all-cause deaths and the composite outcome, across four propensity-score matched treatment cohorts with >15400 patients each. Over 2.9±1.5 years, the incidence of IS and IS/SE was slightly less with VKAs than with DOACs (1.62 and 1.84 vs 1.81 and 1.99 events.100 person-years; HR=0.85, 95%CI=0.76-0.95 and HR=0.87, 95%CI=0.78-0.97). This difference disappeared in a sensitivity analysis which excluded those patients treated with low-dose of apixaban, edoxaban, or rivaroxaban (41.7% of DOACs cohort). Compared with DOACs, VKAs were associated with greater incidence of ICH (1.09 vs 0.81; HR=1.38, 95%CI=1.17-1.62), MB (3.78 vs 3.31; HR=1.14, 95%CI=1.02-1.28), all-cause mortality (9.66 vs 10.10; HR=1.07, 95%CI=1.02-1.11), and composite outcome (13.72 vs 13.32; HR=1.04, 95%CI=1.01-1.08). IS, IS/SE, and mortality were more frequent with ASA or No Tx than with VKAs or DOACs (p<0.001 for all comparisons).
CONCLUSIONS
Beyond confirming the association with a better net clinical benefit of DOACs over VKAs, our findings substantiate the large proportion of NVAF patients still inappropriately anticoagulated, thereby reinforcing the need for educational programs.
Topics: Humans; Female; Aged; Male; Atrial Fibrillation; Stroke; Anticoagulants; Rivaroxaban; Ischemic Stroke; Intracranial Hemorrhages; Aspirin; Gastrointestinal Hemorrhage; Administration, Oral; Dabigatran
PubMed: 37879969
DOI: 10.1016/j.ejim.2023.10.010 -
Deutsche Medizinische Wochenschrift... Sep 2023Prescribing oral anticoagulation in older patients for e.g. stroke prophylaxis has proven to be beneficial, but some special risks have to be considered. Renal function...
Prescribing oral anticoagulation in older patients for e.g. stroke prophylaxis has proven to be beneficial, but some special risks have to be considered. Renal function may be substantial impaired and dose reduction in at least some of the substances is recommended. Therefore, a closer monitoring of renal function is essential. Further as bleeding risk also increases with age usual scoring lists do less help this therapeutic dilemma than in younger patients. Adequate blood pressure control is essential in preventing intracerebral hemorrhage. Fall risk has to be assessed to initiate early compensation for this risk. Only high and unimprovable fall incidence may outweigh the benefits of oral anticoagulation therapy (>1 hospital admission per month due to a fall incident). Comprehensive geriatric assessment is crucial for early detection of specific adherence problems in older patients and is also helpful for discussion of individual deprescribing options in an end of live situation.
Topics: Humans; Aged; Blood Pressure; Cerebral Hemorrhage; Geriatric Assessment; Hospitalization; Anticoagulants
PubMed: 37611574
DOI: 10.1055/a-2020-0196 -
Archives of Dermatological Research Aug 2023There is little clarity about the clinical manifestations of dermatomyositis (DM) in the periungual folds, scalp, and oral cavity and their association with disease... (Observational Study)
Observational Study
There is little clarity about the clinical manifestations of dermatomyositis (DM) in the periungual folds, scalp, and oral cavity and their association with disease activity and damage. The objective of this study was to compare the prevalence of trichoscopic, oral, and periungual changes between DM and healthy patients and assess their possible association with disease activity and damage. We conducted an observational, transversal, and analytical study between 2020 and 2021. Forty DM patients were matched by sex and age with 40 healthy individuals. On the same day, all patients had a clinical evaluation of the hands, periungual folds, scalp, and oral cavity. Photographs of these areas and peripheral venous blood tests, including myositis-associated (MAAs) and myositis-specific antibodies (MSAs), were taken. Two dermatologists blinded to their diagnosis, damage, and activity levels registered the lesions. The disease activity and damage were evaluated using the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI). The presence of mechanic's hands, Gottron's sign, and Gottron's papules in hands; capillary dilation, capillary tortuosity, cuticular hemorrhage, avascular areas, and cuticular hyperkeratosis in periungual folds; thick tortuous capillaries in scalp; gingival telangiectasias in the oral cavity; and positive MSAs associated with severe cutaneous involvement in DM patients (Anti-TIF1g, Anti-MDA5, Anti-SAE1/2) were associated with a higher CDASI activity score. The presence of MSAs associated with intense muscle involvement in DM patients (Anti-Mi2a, Anti-Mi2b, Anti-NPX2, and Anti-SAE1/2) was related to a lower CDASI activity score. Gottron's sign and Gottron's papules in hands; capillary dilation, capillary tortuosity, cuticular hemorrhage, avascular areas, and cuticular hyperkeratosis in periungual folds; basal erythema in scalp; and gingival telangiectasias in the oral cavity were associated with a higher CDASI damage score. There are trichoscopic, oral and periungual fold findings and some myositis-specific antibodies that correlate with disease activity and damage in DM patients.
Topics: Humans; Dermatomyositis; Paraneoplastic Syndromes; Prevalence; Dermoscopy; Oral Manifestations; Nails; Case-Control Studies; Male; Female; Adult; Middle Aged; Aged; Autoantibodies
PubMed: 36757439
DOI: 10.1007/s00403-023-02554-0 -
The American Journal of Cardiology Nov 2023Direct oral anticoagulants (DOACs) are a newer class of anticoagulants that inhibit factor Xa or factor IIa and include drugs such as rivaroxaban, apixaban, edoxaban,... (Meta-Analysis)
Meta-Analysis
An Evidence-Based Approach to Anticoagulation Therapy Comparing Direct Oral Anticoagulants and Vitamin K Antagonists in Patients With Atrial Fibrillation and Bioprosthetic Valves: A Systematic Review, Meta-Analysis, and Network Meta-Analysis.
Direct oral anticoagulants (DOACs) are a newer class of anticoagulants that inhibit factor Xa or factor IIa and include drugs such as rivaroxaban, apixaban, edoxaban, betrixaban, and dabigatran. Although vitamin K antagonists (VKAs) have been traditionally used to prevent thromboembolic events, DOACs have gained popularity because of their faster onset and offset of action and reduced need for monitoring. This study aimed to provide more data for anticoagulants in patients with atrial fibrillation with bioprosthetic heart valves by incorporating all available trials to date. A search was performed across 5 electronic databases to identify relevant studies. We analyzed the data using a pooled risk ratio for categorical outcomes and used the I test to determine heterogeneity. The quality of randomized controlled trials was assessed using the Cochrane risk of bias assessment tool, and the National Institutes of Health tool was used for observational studies. Our study included a frequentist network meta-analysis (MA) of the aggregate data to obtain the network estimates for the outcomes of interest. We retrieved 28 studies with a total of 74,660 patients with bioprosthetic heart valves. Our MA significantly showed that DOACs decrease the risk of all-cause bleeding (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.75 to 0.85, p >0.00001), stroke and systemic embolization (RR 0.89, 95% CI 0.80 to 0.99, p = 0.03), and intracranial bleeding outcomes (RR 0.62, 95% CI 0.45 to 0.86, p = 0.004) compared with VKA. In contrast, there was no significant difference between the compared groups in major bleeding (RR = 0.92, 95% CI 0.84 to 1.02, p = 0.10) and all-cause mortality outcomes (RR = 0.96, 95% CI 0.85 to 1.07, p = 0.43), respectively. In addition, the network MA results did not favor any of the studied interventions over each other (p <0.05) regarding all-cause bleeding, mortality, stroke and systemic embolization, and major bleeding outcomes. In conclusion, our study found that DOACs are more effective in reducing the risk of bleeding, stroke, systemic embolism, and intracranial bleeding than VKAs. However, no significant difference was observed in the incidence of gastrointestinal bleeding, major bleeding, thromboembolic events, and all-cause mortality. In addition, our network MA did not identify any specific DOAC treatment as more favorable than others.
Topics: Humans; Atrial Fibrillation; Network Meta-Analysis; Anticoagulants; Hemorrhage; Stroke; Thromboembolism; Fibrinolytic Agents; Intracranial Hemorrhages; Vitamin K; Administration, Oral
PubMed: 37703679
DOI: 10.1016/j.amjcard.2023.07.141 -
British Journal of Clinical Pharmacology Aug 2023Drug-drug interactions (DDIs) are common in cancer management and complicate the choice of anticoagulation in cancer-associated thrombosis. Cancer confers an increased... (Review)
Review
Drug-drug interactions (DDIs) are common in cancer management and complicate the choice of anticoagulation in cancer-associated thrombosis. Cancer confers an increased risk of thrombotic events. Also, more bleeding events are observed in those who receive anticoagulation compared to those without cancer. In the treatment of cancer-associated thrombosis, direct oral anticoagulants (DOACs) have been found to be at least as effective as low-molecular weight heparins, which became the standard of care after several trials demonstrated superiority over vitamin K antagonists. Non-inferiority compared to low-molecular weight heparins has been shown for rivaroxaban, edoxaban and apixaban with a signal of fewer recurrent thrombotic events, albeit with an increase in bleeding events. Yet, potentially major pharmacokinetic drug-drug interactions have been identified as a reason to withhold DOACs and to rather choose an alternative. Practical guidance on what constitutes a major pharmacokinetic interaction and/or how to deal with these interactions in clinical practice is limited. Hence, here we have provided a framework to allow clinicians to better deal with pharmacokinetic drug-drug interactions between DOACs and cancer therapies in the management of cancer-associated thrombosis. In this review we have discussed the current literature, how the pharmacokinetic profile links to the label information on DDI, and have provided a practical proposal, applied to a clinical case.
Topics: Humans; Anticoagulants; Rivaroxaban; Thrombosis; Hemorrhage; Heparin, Low-Molecular-Weight; Drug Interactions; Administration, Oral; Venous Thromboembolism; Neoplasms
PubMed: 37170893
DOI: 10.1111/bcp.15785 -
Journal of Nanobiotechnology Nov 2023Rapid hemostasis of uncontrolled bleeding following traumatic injuries, especially accompanied by coagulopathies, remains a significant clinical challenge. Extracellular...
Rapid hemostasis of uncontrolled bleeding following traumatic injuries, especially accompanied by coagulopathies, remains a significant clinical challenge. Extracellular vesicles (EVs) show therapeutic effects for fast clotting. However, low yield, specific storage conditions, and lack of proper carriers have hindered EVs' clinical application. Herein, we establish an optimized procedure method to generate lyophilized mesenchymal stem cell-derived apoptotic vesicles (apoVs) with adhesive hydrogel sponge to show superior procoagulant activity for traumatic hemorrhage. Mechanistically, apoVs' procoagulant ability stems from their high tissue factor (TF) and phosphatidylserine (PS) expression independent of hemocytes and circulating procoagulant microparticles (cMPs). Their stable hemostatic capability was maintained after 2-month room temperature storage. Subsequently, we mixed apoVs with both phenylboronic acid grafted oxidized hyaluronic acid (PBA-HA) and poly(vinyl alcohol) (PVA) simultaneously, followed by lyophilization to construct a novel apoV-encapsulated hydrogel sponge (apoV-HS). Compared to commercial hemostats, apoV-HS exhibits rapid procoagulant ability in liver-laceration and femoral artery hemorrhage in rat and rabbit models of coagulopathies. The combination of high productivity, physiological stability, injectability, plasticity, excellent adhesivity, biocompatibility, and rapid coagulant property indicates that apoV-HS is a promising therapeutic approach for heavy hemorrhage in civilian and military populations.
Topics: Rats; Animals; Rabbits; Adhesives; Hydrogels; Hemostatics; Hemorrhage; Extracellular Vesicles
PubMed: 37924105
DOI: 10.1186/s12951-023-02128-2 -
Thrombosis and Haemostasis Jul 2023The aim of the present meta-analysis was to evaluate the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists...
BACKGROUND
The aim of the present meta-analysis was to evaluate the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with polypharmacy.
METHODS AND RESULTS
Randomized controlled trials or observational studies reporting the data of NOACs versus VKAs among AF patients with polypharmacy were included. The search was performed in the PubMed and Embase databases up to November 2022. A total of 12 studies involving 767,544 AF patients were included. For the primary outcomes, the use of NOACs compared with VKAs was significantly associated with a reduced risk of stroke or systemic embolism in AF patients with moderate polypharmacy (hazard ratio [HR]: 0.77 [95% confidence interval [CI]: 0.69-0.86]) and severe polypharmacy (HR: 0.76 [95% CI: 0.69-0.82]), but there was no significant difference in major bleeding (moderate polypharmacy: HR: 0.87 [95% CI: 0.74-1.01]; severe polypharmacy: HR: 0.91 [95% CI: 0.79-1.06]) between the two groups. In secondary outcomes, there were no differences in the rates of ischemic stroke, all-cause death, and gastrointestinal bleeding between the NOAC- and VKA- users, but NOAC users had a reduced risk of any bleeding compared with VKA- users. Compared with VKAs, the risk of intracranial hemorrhage was reduced in NOAC- users with moderate polypharmacy but not severe polypharmacy.
CONCLUSION
In patients with AF and polypharmacy, NOACs showed advantages over VKAs in stroke or systemic embolism and any bleeding, and were comparable to VKAs for major bleeding, ischemic stroke, all-cause death, intracranial hemorrhage, and gastrointestinal bleeding.
PubMed: 37399842
DOI: 10.1055/s-0043-1770724 -
European Journal of Cardio-thoracic... Oct 2023Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize... (Review)
Review
OBJECTIVES
Literature is scarce on the management of patients using direct oral anticoagulants (DOACs) undergoing elective, urgent and emergency surgery. Therefore, we summarize the current evidence and provide literature-based recommendations for the management of patients on DOACs in the perioperative phase.
METHODS
A general literature review was conducted on the pharmacology of DOACs and for recommendations on the management of cardiac surgical patients on DOACs. Additionally, we performed a systematic review for studies on the use of direct DOAC reversal agents in the emergency cardiac surgical setting.
RESULTS
When surgery is elective, the DOAC cessation strategy is relatively straightforward and should be adapted to the renal function. The same approach applies to urgent cases, but additional DOAC activity drug level monitoring tests may be useful. In emergency cases, idarucizumab can be safely administered to patients on dabigatran in any of the perioperative phases. However, andexanet alfa, which is not registered for perioperative use, should not be administered in the preoperative phase to reverse the effect of factor Xa inhibitors, as it may induce temporary heparin resistance. Finally, the administration of (activated) prothrombin complex concentrate may be considered in all patients on DOACs, and such concentrates are generally readily available.
CONCLUSIONS
DOACs offer several advantages over vitamin K antagonists, but care must be taken in patients undergoing cardiac surgery. Although elective and urgent cases can be managed relatively straightforwardly, the management of emergency cases requires particular attention.
Topics: Humans; Administration, Oral; Anticoagulants; Cardiac Surgical Procedures; Dabigatran; Hemorrhage; Heparin
PubMed: 37812245
DOI: 10.1093/ejcts/ezad340 -
Hypertension Research : Official... Dec 2023The benefits of direct oral anticoagulants (DOACs) and warfarin in elderly Japanese patients with non-valvular atrial fibrillation (NVAF) and high home systolic blood...
Anticoagulant therapy and home blood pressure-associated risk for stroke/bleeding events in elderly patients with non-valvular atrial fibrillation: the sub-cohort study of ANAFIE registry.
The benefits of direct oral anticoagulants (DOACs) and warfarin in elderly Japanese patients with non-valvular atrial fibrillation (NVAF) and high home systolic blood pressure (H-SBP) are unclear. This sub-cohort study of the ANAFIE Registry estimated the incidence of clinical outcomes in patients receiving anticoagulant therapy (warfarin and DOACs) stratified by H-SBP levels (<125 mmHg, ≥125-<135 mmHg, ≥135-<145 mmHg and ≥145 mmHg). Of the overall ANAFIE population, 4933 patients who underwent home blood pressure (H-BP) measurements were analyzed; 93% received OACs (DOACs: 3494, 70.8%; warfarin: 1092, 22.1%). In the warfarin group, at <125 mmHg and ≥145 mmHg, the respective incidence rates (per 100 person-years) were 1.91 and 5.89 for net cardiovascular outcome (a composite of stroke/systemic embolic events (SEE) and major bleeding), 1.31 and 3.39 for stroke/SEE, 0.59 and 3.91 for major bleeding, 0.59 and 3.43 for intracranial hemorrhage (ICH), and 4.01 and 6.24 for all-cause death. Corresponding incidence rates in the DOACs group were 1.64 and 2.65, 1.00 and 1.88, 0.78 and 1.69, 0.55 and 1.31, and 3.43 and 3.51. In warfarin-treated patients, the incidence rates of net cardiovascular outcome, stroke/SEE, major bleeding, and ICH were significantly increased at H-SBP ≥ 145 mmHg versus <125 mmHg. In the DOAC group, although there was no significant difference between H-SBP < 125 mmHg and ≥145 mmHg, the incidence rates of these events tended to increase at ≥145 mmHg. These results suggest that strict BP control guided by H-BP is required in elderly NVAF patients receiving anticoagulant therapy.
Topics: Humans; Aged; Warfarin; Atrial Fibrillation; Cohort Studies; Blood Pressure; Risk Factors; Administration, Oral; Anticoagulants; Stroke; Hemorrhage; Registries
PubMed: 37433904
DOI: 10.1038/s41440-023-01361-4 -
Journal of Clinical Medicine Sep 2023Atrial fibrillation (AF) is an important risk factor for ischemic stroke (IS). Oral anticoagulation (OAC) significantly reduces the risk of IS in AF but also increases... (Review)
Review
Atrial fibrillation (AF) is an important risk factor for ischemic stroke (IS). Oral anticoagulation (OAC) significantly reduces the risk of IS in AF but also increases the risk of systemic bleeding, including intracerebral hemorrhage (ICH). AF-related strokes are associated with greater disability and mortality compared to non-AF strokes. The management of patients with AF-related strokes is challenging, and it involves weighing individual risks and benefits in the acute treatment and preventive strategies of these patients. This review summarizes the current knowledge of the acute management of ischemic and hemorrhagic stroke in patients with AF, and the prognosis and potential implications for management both in the acute and long-term setting.
PubMed: 37685819
DOI: 10.3390/jcm12175752