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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 -
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 -
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 -
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 -
International Journal of Stroke :... Dec 2023An increased risk of intracranial hemorrhage (ICH) associated with statins has been reported, but data on the relationship between statin use and cerebral microbleeds...
BACKGROUND
An increased risk of intracranial hemorrhage (ICH) associated with statins has been reported, but data on the relationship between statin use and cerebral microbleeds (CMBs) in patients with atrial fibrillation (AF), a population at high bleeding and cardiovascular risk, are lacking.
AIMS
To explore the association between statin use and blood lipid levels with the prevalence and progression of CMBs in patients with AF with a particular focus on anticoagulated patients.
METHODS
Data of Swiss-AF, a prospective cohort of patients with established AF, were analyzed. Statin use was assessed during baseline and throughout follow-up. Lipid values were measured at baseline. CMBs were assessed using magnetic resonance imagining (MRI) at baseline and at 2 years follow-up. Imaging data were centrally assessed by blinded investigators. Associations of statin use and low-density lipoprotein (LDL) levels with CMB prevalence at baseline or CMB progression (at least one additional or new CMB on follow-up MRI at 2 years compared with baseline) were assessed using logistic regression models; the association with ICH was assessed using flexible parametric survival models. Models were adjusted for hypertension, smoking, body mass index, diabetes, stroke/transient ischemic attack, coronary heart disease, antiplatelet use, anticoagulant use, and education.
RESULTS
Of the 1693 patients with CMB data at baseline MRI (mean ± SD age 72.5 ± 8.4 years, 27.6% women, 90.1% on oral anticoagulants), 802 patients (47.4%) were statin users. The multivariable adjusted odds ratio (adjOR) for CMBs prevalence at baseline for statin users was 1.10 (95% CI = 0.83-1.45). AdjOR for 1 unit increase in LDL levels was 0.95 (95% CI = 0.82-1.10). At 2 years, 1188 patients had follow-up MRI. CMBs progression was observed in 44 (8.0%) statin users and 47 (7.4%) non-statin users. Of these patients, 64 (70.3%) developed a single new CMB, 14 (15.4%) developed 2 CMBs, and 13 developed more than 3 CMBs. The multivariable adjOR for statin users was 1.09 (95% CI = 0.66-1.80). There was no association between LDL levels and CMB progression (adjOR 1.02, 95% CI = 0.79-1.32). At follow-up 14 (1.2%) statin users had ICH versus 16 (1.3%) non-users. The age and sex adjusted hazard ratio (adjHR) was 0.75 (95% CI = 0.36-1.55). The results remained robust in sensitivity analyses excluding participants without anticoagulants.
CONCLUSIONS
In this prospective cohort of patients with AF, a population at increased hemorrhagic risk due to anticoagulation, the use of statins was not associated with an increased risk of CMBs.
Topics: Humans; Female; Middle Aged; Aged; Aged, 80 and over; Male; Stroke; Atrial Fibrillation; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cerebral Hemorrhage; Prospective Studies; Intracranial Hemorrhages; Anticoagulants; Risk Factors; Magnetic Resonance Imaging
PubMed: 37243540
DOI: 10.1177/17474930231181010 -
Frontiers in Pharmacology 2023A lack of clarity persists regarding the efficacy and risks associated with direct oral anticoagulants (DOACs) in end-stage renal disease (ESRD) patients with atrial...
A lack of clarity persists regarding the efficacy and risks associated with direct oral anticoagulants (DOACs) in end-stage renal disease (ESRD) patients with atrial fibrillation (AF) undergoing dialysis, primarily due to limited retrospective studies. Therefore, the objective of this study was to evaluate the existing data and propose a practical protocol for the clinical utilization of DOACs in ESRD patients with AF undergoing dialysis. PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for clinical studies evaluating DOACs in ESRD patients with AF on dialysis published up to 2 February 2023. DOACs included warfarin, dabigatran, apixaban, edoxaban, and rivaroxaban. The outcomes were mortality, ischemic stroke, hemorrhagic stroke, any stroke, gastrointestinal bleeding, major bleeding, intracranial bleeding, and minor bleeding. Compared with placebo, apixaban (HR = 0.97, 95% CI: 0.88-1.07), rivaroxaban (HR = 0.91, 95% CI: 0.76-1.10), and warfarin (HR = 0.96, 95% CI: 0.90-1.01) did not reduce mortality. Regarding direct comparisons of mortality, the comparisons of warfarin vs. apixaban (HR = 0.99, 95% CI: 0.92-1.06), placebo vs. warfarin (HR = 1.04, 95% CI: 0.99-1.11), and rivaroxaban vs. warfarin (HR = 0.96, 95% CI: 0.80-1.14) did not significantly reduce mortality. Based on the surface under the cumulative ranking curve, rivaroxaban (75.53%), warfarin (62.14%), and apixaban (45.6%) were the most effective interventions for managing mortality, and placebo (16.74%) was the worst. In conclusion, rivaroxaban demonstrated efficacy in reducing mortality and the incidence of ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage. Dabigatran is recommended for the prevention of hemorrhagic stroke. However, caution should be exercised due to the risk of major bleeding. Warfarin can effectively reduce minor bleeding but does not offer significant protection against gastrointestinal or intracranial bleeding. Apixaban was not recommended for mortality reduction or for preventing ischemic or hemorrhagic strokes. Further research will be necessary to establish specific clinical protocols.
PubMed: 38161701
DOI: 10.3389/fphar.2023.1320939 -
Revista Do Colegio Brasileiro de... 2023hepatocellular adenoma - AHC - is a rare benign neoplasm of the liver more prevalent in women at reproductive age and its main complication is hemorrhage. In the...
INTRODUCTION
hepatocellular adenoma - AHC - is a rare benign neoplasm of the liver more prevalent in women at reproductive age and its main complication is hemorrhage. In the literature, case series addressing this complication are limited.
METHODS
between 2010 and 2022, 12 cases of bleeding AHC were attended in a high-complexity university hospital in southern Brazil, whose medical records were retrospectively evaluated.
RESULTS
all patients were female, with a mean age of 32 years and a BMI of 33kg/m2. The use of oral contraceptives was identified in half of the sample and also half of the patients had a single lesion. The mean diameter of the largest lesion was 9.60cm and the largest lesion was responsible for bleeding in all cases. The presence of hemoperitoneum was documented in 33% of the patients and their age was significantly higher than the patients who did not have hemoperitoneum - 38 vs 30 years, respectively. Surgical resection of the bleeding lesion was performed in 50% of the patients and the median number of days between bleeding and resection was 27 days. In only one case, embolization was used. The relation between ingrowth of the lesions and the time, in months, was not obtained in this study.
CONCLUSION
it is concluded that the bleeding AHC of the present series shows epidemiological agreement with the literature and may suggest that older patients trend to have hemoperitoneum more frequently, a fact that should be investigated in further studies.
Topics: Humans; Female; Adult; Male; Adenoma, Liver Cell; Liver Neoplasms; Carcinoma, Hepatocellular; Hemoperitoneum; Retrospective Studies
PubMed: 37436285
DOI: 10.1590/0100-6991e-20233549-en -
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 -
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 -
Journal of Thrombosis and Thrombolysis Nov 2023The effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and advanced kidney disease (AKD) has not been fully...
BACKGROUND
The effectiveness and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and advanced kidney disease (AKD) has not been fully established.
OBJECTIVES
To determine the effectiveness and safety related to pooled or specific DOACs to that with warfarin in patients with AF and AKD.
METHODS
Patients with AF and AKD (estimated glomerular filtration rate < 30 mL/min) who received DOAC or warfarin from July 2011 to December 2020 were retrospectively identified in a medical center in Taiwan. Primary outcomes were hospitalized for stroke/systemic embolism and major bleeding. Secondary outcomes included any ischemia and any bleeding.
RESULTS
A total of 1,011 patients were recruited, of whom 809 (80.0%) were in the DOACs group (15.3% dabigatran, 25.4% rivaroxaban, 25.2% apixaban, and 14.1% edoxaban), and 202 (20.0%) in the warfarin group. DOACs had considerably lower risks of stroke/systemic embolism (adjusted hazard ratio [aHR] 0.29; 95% CI, 0.09-0.97) and any ischemia (aHR, 0.42; 95% CI, 0.22-0.79), but had comparable risks of major bleeding (aHR, 0.99; 95% CI, 0.34-2.92) and any bleeding (aHR, 0.74; 95% CI, 0.50-1.09) than warfarin. Apixaban was linked to considerably lower risks of any ischemia (aHR, 0.13; 95% CI, 0.04-0.48) and any bleeding (aHR, 0.53; 95% CI, 0.28-0.99) than warfarin.
CONCLUSION
Among patients with AF and AKD, DOACs were linked to a lower risk of ischemic events, and apixaban was linked to a lower risk of any ischemia and any bleeding than warfarin.
PubMed: 37452906
DOI: 10.1007/s11239-023-02859-x