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JAMA Internal Medicine Jan 2024Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Current guidelines advise against intravenous alteplase therapy for treatment of acute ischemic stroke in patients previously treated with non-vitamin K antagonist oral anticoagulants (NOACs).
OBJECTIVE
To evaluate the risk of bleeding and mortality after alteplase treatment for acute ischemic stroke among patients treated with NOACs compared to those not treated with NOACs.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide, population-based cohort study was conducted in Taiwan using data from Taiwan's National Health Insurance Research Database from January 2011 through November 2020 and included 7483 patients treated with alteplase for acute ischemic stroke. A meta-analysis incorporating the results of the study with those of previous studies was performed, and the review protocol was prospectively registered with PROSPERO.
EXPOSURES
NOAC treatment within 2 days prior to stroke, compared to either no anticoagulant treatment or warfarin treatment.
MAIN OUTCOMES AND MEASURES
The primary outcome was intracranial hemorrhage after intravenous alteplase during the index hospitalization (the hospitalization subsequent to alteplase administration). Secondary outcomes were major bleeding events and mortality during the index hospitalization. Propensity score matching was used to control potential confounders. Logistic regression was used to estimate the odds ratio (OR) of outcome events. Meta-analysis was performed using a random-effects model.
RESULTS
Of the 7483 included patients (mean [SD] age, 67.4 [12.7] years; 2908 [38.9%] female individuals and 4575 [61.1%] male individuals), 91 (1.2%), 182 (2.4%), and 7210 (96.4%) received NOACs, warfarin, and no anticoagulants prior to their stroke, respectively. Compared to patients who were not treated with anticoagulants, those treated with NOACs did not have significantly higher risks of intracranial hemorrhage (risk difference [RD], 2.47% [95% CI, -4.23% to 9.17%]; OR, 1.37 [95% CI, 0.62-3.03]), major bleeding (RD, 4.95% [95% CI, -2.56% to 12.45%]; OR, 1.69 [95% CI, 0.83-3.45]), or in-hospital mortality (RD, -4.95% [95% CI, -10.11% to 0.22%]; OR, 0.45 [95% CI, 0.15-1.29]) in the propensity score-matched analyses. Furthermore, the risks of bleeding and mortality were not significantly different between patients treated with NOACs and those treated with warfarin. Similar results were obtained in the meta-analysis.
CONCLUSIONS AND RELEVANCE
In this cohort study with meta-analysis, compared to no treatment with anticoagulants, treatment with NOACs prior to stroke was not associated with a higher risk of intracranial hemorrhage, major bleeding, or mortality in patients receiving intravenous alteplase for acute ischemic stroke.
Topics: Humans; Male; Female; Aged; Anticoagulants; Warfarin; Tissue Plasminogen Activator; Ischemic Stroke; Cohort Studies; Administration, Oral; Atrial Fibrillation; Hemorrhage; Stroke; Intracranial Hemorrhages
PubMed: 37983035
DOI: 10.1001/jamainternmed.2023.6160 -
Journal of the American Medical... Aug 2023To evaluate the efficacy and safety of oral anticoagulants for older adult patients with atrial fibrillation (AF). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of oral anticoagulants for older adult patients with atrial fibrillation (AF).
DESIGN
Pairwise and network meta-analyses.
SETTING AND PARTICIPANTS
Patients with AF aged ≥75 years.
METHODS
PubMed, Embase, and the Cochrane library were searched for published randomized controlled trials and adjusted observational studies evaluating the use of a non-vitamin K antagonist oral anticoagulants (NOACs), vitamin K antagonist, or antiplatelet drug for the prevention of stroke. The primary efficacy and safety outcomes were the composite of stroke and systemic embolism (SSE) and major bleedings.
RESULTS
This study included 38 studies enrolling 1,022,908 older adult patients with AF. Results from pairwise meta-analyses showed that NOACs were superior to warfarin for all outcomes, except that dabigatran increased the risk of gastrointestinal (GI) bleedings. Aspirin was associated with a higher risk of SSE and ischemic stroke than warfarin or NOACs. Results of network meta-analyses indicated that apixaban significantly reduced the risk of SSE, major bleedings, and GI bleedings than warfarin, rivaroxaban, and dabigatran. Apixaban, edoxaban, rivaroxaban, and dabigatran reduced the risk of ischemic stroke and intracranial bleeding compared to warfarin. Dabigatran showed lower risk of all-cause mortality than warfarin and of intracranial bleeding than rivaroxaban.
CONCLUSIONS AND IMPLICATIONS
NOACs are of at least equal efficacy, or even superior to warfarin. The safety profile of individual NOAC agents was significantly different, as apixaban performs better than the other oral anticoagulants in reducing major bleeding and GI bleeding, whereas dabigatran increased the risk of GI bleeding.
Topics: Aged; Humans; Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Hemorrhage; Ischemic Stroke; Network Meta-Analysis; Rivaroxaban; Stroke; Warfarin
PubMed: 37355246
DOI: 10.1016/j.jamda.2023.05.010 -
European Heart Journal. Cardiovascular... Dec 2023The Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial showed that edoxaban at a very low dosage (VLD) of 15 mg/day was more effective...
Clinical outcomes in elderly atrial fibrillation patients at increased bleeding risk treated with very low dose vs. regular-dose non-vitamin K antagonist oral anticoagulants: a nationwide cohort study.
AIMS
The Edoxaban Low-Dose for Elder Care Atrial Fibrillation Patients (ELDERCARE-AF) trial showed that edoxaban at a very low dosage (VLD) of 15 mg/day was more effective than a placebo at preventing stroke/systemic embolism without significantly increasing the risk of serious bleeding. We aimed to compare the effectiveness and safety for VLD non-vitamin K antagonist oral anticoagulants (NOACs) [edoxaban 15 mg o.d., dabigatran 110 or 150 o.d., apixaban 2.5 mg o.d., or rivaroxaban 10 mg (without the diagnosis of chronic kidney disease) or <10 mg o.d.] vs. regular-dosage (RD) NOACs (edoxaban 60/30 mg o.d. or other labeling-dosage NOACs) among a real-world cohort of elderly atrial fibrillation (AF) population similar to the ELDERCARE-AF cohort.
METHODS AND RESULTS
In this nationwide retrospective cohort study from Taiwan National Health Insurance Research Database (NHIRD), we identified a total of 7294 and 4151 consecutive AF patients aged 80 years or older with a CHADS2 (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, previous stroke/transient ischemic attack (2 points) score ≥2 who met the enrollment criteria (generally similar to ELDERCARE-AF) taking VLD and RD NOACs from 1 June 2012 to 31 December 2019, respectively. Propensity-score stabilized weighting (PSSW) was used to balance covariates across study groups. Patients were followed up from the first date of prescription for NOACs until the first occurrence of any study outcome, death, or until the end date of the study period (31 December 2020). After PSSW, VLD NOAC was associated with a comparable risk of ischemic stroke/systemic embolism and major bleeding but a higher risk of major adverse limb events (MALEs) requiring lower limb revascularization or amputation [hazard ratio (HR): 1.54, 95% confidential interval (CI): 1.09-2.18; P = 0.014), venous thrombosis (HR: 3.75, 95% CI: 1.56-8.97; P = 0.003), and all-cause mortality (HR: 1.21, 95% CI: 1.15-1.29; P <0.001) compared with RD NOACs. VLD NOACs showed worse outcomes in most net clinical outcome (NCO) benefits. The main result was consistent based on on-treatment analysis or accounting for death as a competing risk. In general, the advantage of NCOs for the RD NOACs over VLD NOACs persisted in most high-risk subgroups, consistent with the main analysis (P for interaction > 0.05).
CONCLUSION
Use of VLD NOACs was associated with a greater risk of arterial and venous thrombosis, death as well as the composite outcomes, when compared with that of RD NOAC in high-risk elderly AF patients at increased bleeding risk. Thromboprophylaxis with RD NOAC is still preferable over VLD NOAC for the majority of elderly AF patients at increased bleeding risk.
Topics: Aged; Male; Humans; Anticoagulants; Atrial Fibrillation; Warfarin; Cohort Studies; Retrospective Studies; Administration, Oral; Treatment Outcome; Venous Thromboembolism; Hemorrhage; Stroke; Venous Thrombosis; Embolism
PubMed: 37580139
DOI: 10.1093/ehjcvp/pvad058 -
Methodist DeBakey Cardiovascular Journal 2024Pulmonary embolus (PE) carries a significant impending morbidity and mortality, especially in intermediate and high-risk patients, and the choice of initial... (Review)
Review
Pulmonary embolus (PE) carries a significant impending morbidity and mortality, especially in intermediate and high-risk patients, and the choice of initial anticoagulation that allows for therapeutic adjustment or manipulation is important. The preferred choice of anticoagulation management includes direct oral anticoagulants. Vitamin K antagonists and low-molecular-weight heparin are preferred in special populations or selected patients such as breastfeeding mothers, those with end-stage renal disease, or obese patients, among others. This article reviews the primary and longer-term considerations for anticoagulation management in patients with PE and highlights special patient populations and risk factor considerations.
Topics: Humans; Pulmonary Embolism; Anticoagulants; Risk Factors; Treatment Outcome; Blood Coagulation; Administration, Oral; Risk Assessment; Hemorrhage; Vitamin K; Clinical Decision-Making
PubMed: 38765210
DOI: 10.14797/mdcvj.1338 -
Journal of the American Heart... Dec 2023Although older patients with atrial fibrillation are at heightened risk of thromboembolic and bleeding events, their optimal treatment choice remains uncertain. (Meta-Analysis)
Meta-Analysis
Efficacy and Safety of Direct Oral Anticoagulants for Stroke Prevention in Older Patients With Atrial Fibrillation: A Network Meta-Analysis of Randomized Controlled Trials.
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.
Topics: Humans; Aged; Atrial Fibrillation; Rivaroxaban; Dabigatran; Network Meta-Analysis; Randomized Controlled Trials as Topic; Anticoagulants; Stroke; Hemorrhage; Embolism; Intracranial Hemorrhages; Administration, Oral
PubMed: 38014696
DOI: 10.1161/JAHA.123.030380 -
Brain Sciences Oct 2023The pituitary gland, a puzzling medical subject up until the 20th century, had its early pathologies first documented in the 19th century by Pierre Marie and Hutchinson,...
The pituitary gland, a puzzling medical subject up until the 20th century, had its early pathologies first documented in the 19th century by Pierre Marie and Hutchinson, where the gland's meaningful study was hindered by its hard-to-reach location. This paper revisits the pioneering work of Romanian doctors such as Gheorghe Marinescu, Nicolae Paulescu, and Grigore T. Popa in surgical techniques targeting the pituitary gland. Marinescu's 1892 experiment, albeit unsuccessful, laid the groundwork for future research in this area. Before Paulescu, surgical attempts could be classified into three types: oral, cranial, and sphenopalatine fossa approaches-all of which were notably dangerous and often resulted in fatal bleeding. Paulescu was the first to successfully and safely perform a complete in vivo hypophysectomy, opting for an innovative subtemporal method. He also conducted extensive research over four years to identify the gland's essential functions. Later, a 1938 study by Popa and Harris demonstrated a temporal approach to the hypothalamo-hypophysial region in a rabbit. These groundbreaking contributions significantly influenced the trajectory of pituitary gland surgery.
PubMed: 37891798
DOI: 10.3390/brainsci13101431 -
Journal of Thrombosis and Haemostasis :... Mar 2024Intracranial hemorrhage (ICH) is the most feared and lethal complication of oral anticoagulant (OAC) therapy. Resumption of OAC after ICH has long posed a challenge for... (Review)
Review
Intracranial hemorrhage (ICH) is the most feared and lethal complication of oral anticoagulant (OAC) therapy. Resumption of OAC after ICH has long posed a challenge for clinicians, complicated by the expanding range of anticoagulant agents available in modern clinical practice, including direct OACs and, more recently, factor XI and XII inhibitors. A review of the current literature found support for resuming OAC in the majority of patients after ICH based on pooled retrospective data showing that resumption is associated with a lower risk of mortality and thromboembolism without a significantly increased risk of recurrent hemorrhage. The optimal time to resume OAC is less clear; however, the available evidence suggests that the composite risk of both recurrent hemorrhage and thromboembolism is likely minimized, somewhere between 4 and 6 weeks, after ICH in most patients. Specific considerations to guide the optimal resumption time in the individual patient include ICH location, mechanism, and anticoagulant class. Patients with mechanical heart valves and intracerebral malignancy represent high-risk groups who require more nuanced decision making. Here, we appraise the literature with the aim of providing a practical guide for clinicians while also discussing priorities for future investigation.
Topics: Humans; Retrospective Studies; Atrial Fibrillation; Intracranial Hemorrhages; Anticoagulants; Hemorrhage; Thromboembolism; Administration, Oral; Cerebral Hemorrhage; Stroke
PubMed: 37913910
DOI: 10.1016/j.jtha.2023.10.020 -
Oral Surgery, Oral Medicine, Oral... Dec 2023We examined the range, nature, and extent of research conducted regarding the oral and dental implications of hereditary hemorrhagic telangiectasia (HHT) to identify... (Review)
Review
OBJECTIVE
We examined the range, nature, and extent of research conducted regarding the oral and dental implications of hereditary hemorrhagic telangiectasia (HHT) to identify gaps in the research and knowledge of the field.
STUDY DESIGN
We performed a scoping review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews and 2017 Guidance for the Conduct of Joanna Briggs Institute Scoping Reviews. We searched the MEDLINE and Web of Science databases for all full-text articles published in English from December 1946 to October 2022.
RESULTS
We identified 103 articles describing oral and dental considerations of patients with HHT, primarily case reports. Most reported oral telangiectasias of the tongue, lips, and palate. Many reported management of bleeding and the use or recommendation of prophylactic antibiotics before dental procedures.
CONCLUSIONS
Oral telangiectasias are commonly found in patients with hereditary hemorrhagic telangiectasia, and dental professionals may be the first to diagnose it in their patients. Early detection and diagnosis are important to prevent potentially fatal outcomes, and prophylactic antibiotics before procedures may be warranted.
Topics: Humans; Telangiectasia, Hereditary Hemorrhagic; Telangiectasis; Hemorrhage; Anti-Bacterial Agents
PubMed: 37752017
DOI: 10.1016/j.oooo.2023.08.001 -
Experimental and Clinical... Apr 2024Presently, the management of direct oral anticoagulants lacks specific guidelines for patients before and after transplant, particularly for lung transplant recipients.... (Review)
Review
OBJECTIVES
Presently, the management of direct oral anticoagulants lacks specific guidelines for patients before and after transplant, particularly for lung transplant recipients. We aimed to consolidate the existing literature on direct oral anticoagulants and explore their implications in lung transplant recipients.
MATERIALS AND METHODS
We conducted a comprehensive search in PubMed and Google Scholar databases for studies published between January 2000 and December 2022, using specific search terms. We only included studies involving lung transplant recipients and focusing on direct oral anticoagulants.
RESULTS
Five relevant publications were identified, providing varied insights. None of the studies specifically addressed bleeding complications associated with direct oral anticoagulants in lung transplant recipients. Limited details were available on the type of solid-organ transplant or the specific direct oral anticoagulant used in these studies.
CONCLUSIONS
Varied bleeding complications associated with direct oral anticoagulants in lung transplant recipients were reported, but studies lacked specificity on transplant type and direct oral anticoagulant variations. Notably, the incidence of venous thrombotic embolism in lung transplant recipients was comparatively higher than in other solid-organ transplant recipients, potentially linked to factors such as corticosteroid therapy, calcineurin inhibitors, and cytomegalovirus infections. Our synthesis on findings of use of direct oral anticoagulant in lung transplant recipients emphasized challenges of managing these medications in urgent transplant situations. Recommendations from experts suggested caution in initiation of direct oral anticoagulants posttransplant until stability in renal and hepatic function is achieved. The limited evidence on safety of direct oral anticoagulants in lung transplant recipients underscores the need for further research and guidance in this specific patient population.
Topics: Humans; Lung Transplantation; Administration, Oral; Risk Factors; Treatment Outcome; Hemorrhage; Risk Assessment; Blood Coagulation; Anticoagulants; Factor Xa Inhibitors
PubMed: 38742314
DOI: 10.6002/ect.2023.0338 -
NEJM Evidence Jul 2023Direct oral anticoagulants such as apixaban or dabigatran have revolutionized anticoagulant treatment. These drugs, which specifically inhibit either factor Xa or...
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. 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.
Topics: Humans; Rivaroxaban; Anticoagulants; Warfarin; Dabigatran; Heart Valves
PubMed: 38320170
DOI: 10.1056/EVIDe2300106