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Journal of Clinical Medicine Dec 2023Anticoagulants are a cornerstone of treatment in atrial fibrillation. Nowadays, direct oral anticoagulants (DOACs) are extensively used for this condition in developed... (Review)
Review
Anticoagulants are a cornerstone of treatment in atrial fibrillation. Nowadays, direct oral anticoagulants (DOACs) are extensively used for this condition in developed countries. However, DOAC treatment may be inappropriate in certain patient populations, such as: patients with chronic kidney disease in whom DOAC concentrations may be dangerously elevated; frail elderly patients with an increased risk of falls; patients with significant drug-drug interactions (DDI) affecting either DOAC concentration or effect; patients at the extremes of body mass in whom an "abnormal" volume of distribution may result in inappropriate drug concentrations; patients with recurrent stroke reflecting an unusually high thromboembolic tendency; and, lastly, patients who experience major hemorrhage on an anticoagulant and in whom continued anticoagulation is deemed necessary. Herein we provide a fictional case-based approach to review the recommendations for the use of DOACs in these special patient populations.
PubMed: 38202223
DOI: 10.3390/jcm13010216 -
Stroke Sep 2023Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid... (Randomized Controlled Trial)
Randomized Controlled Trial
Tranexamic Acid for Intracerebral Hemorrhage in Patients on Non-Vitamin K Antagonist Oral Anticoagulants (TICH-NOAC): A Multicenter, Randomized, Placebo-Controlled, Phase 2 Trial.
BACKGROUND
Evidence-based hemostatic treatment for intracerebral hemorrhage (ICH) associated with non-vitamin K antagonist oral anticoagulants (NOACs) is lacking. Tranexamic acid (TXA) is an antifibrinolytic drug potentially limiting hematoma expansion. We aimed to assess the efficacy and safety of TXA in NOAC-ICH.
METHODS
We performed a double-blind, randomized, placebo-controlled trial at 6 Swiss stroke centers. Patients with NOAC-ICH within 12 hours of symptom onset and 48 hours of last NOAC intake were randomized (1:1) to receive either intravenous TXA (1 g over 10 minutes followed by 1 g over 8 hours) or matching placebo in addition to standard medical care via a centralized Web-based procedure with minimization on key prognostic factors. All participants and investigators were masked to treatment allocation. Primary outcome was hematoma expansion, defined as ≥33% relative or ≥6 mL absolute volume increase at 24 hours and analyzed using logistic regression adjusted for baseline hematoma volume on an intention-to-treat basis.
RESULTS
Between December 12, 2016, and September 30, 2021, we randomized 63 patients (median age, 82 years [interquartile range, 76-86]; 40% women; median hematoma volume, 11.5 [4.8-27.4] mL) of the 109 intended sample size before premature trial discontinuation due to exhausted funding. The primary outcome did not differ between TXA (n=32) and placebo (n=31) arms (12 [38%] versus 14 [45%]; adjusted odds ratio, 0.63 [95% CI, 0.22-1.82]; =0.40). There was a signal for interaction with onset-to-treatment time (=0.024), favoring TXA when administered within 6 hours of symptom onset. Between the TXA and placebo arms, the proportion of participants who died (15 [47%] versus 13 [42%]; adjusted odds ratio, 1.07 [0.37-3.04]; =0.91) or had major thromboembolic complications within 90 days (4 [13%] versus 2 [6%]; odds ratio, 1.86 [0.37-9.50]; =0.45) did not differ. All thromboembolic events occurred at least 2 weeks after study treatment, exclusively in participants not restarted on oral anticoagulation.
CONCLUSIONS
In a smaller-than-intended NOAC-ICH patient sample, we found no evidence that TXA prevents hematoma expansion, but there were no major safety concerns. Larger trials on hemostatic treatments targeting an early treatment window are needed for NOAC-ICH.
REGISTRATION
URL: https://clinicaltrials.gov; Unique identifier: NCT02866838.
Topics: Humans; Female; Aged, 80 and over; Male; Tranexamic Acid; Anticoagulants; Administration, Oral; Cerebral Hemorrhage; Antifibrinolytic Agents; Hemostatics; Hematoma; Thromboembolism
PubMed: 37466000
DOI: 10.1161/STROKEAHA.123.042866 -
JAMA Network Open Jul 2023Anticoagulation management services (AMSs; ie, warfarin clinics) have evolved to include patients treated with direct oral anticoagulants (DOACs), but it is unknown...
IMPORTANCE
Anticoagulation management services (AMSs; ie, warfarin clinics) have evolved to include patients treated with direct oral anticoagulants (DOACs), but it is unknown whether DOAC therapy management services improve outcomes for patients with atrial fibrillation (AF).
OBJECTIVE
To compare outcomes associated with 3 DOAC care models for preventing adverse anticoagulation-related outcomes among patients with AF.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included 44 746 adult patients with a diagnosis of AF who initiated oral anticoagulation (DOAC or warfarin) between August 1, 2016, and December 31, 2019, in 3 Kaiser Permanente (KP) regions. Statistical analysis was conducted from August 2021 through May 2023.
EXPOSURES
Each KP region used an AMS to manage warfarin but used distinct approaches to DOAC care: (1) usual care (UC) by the prescribing clinician, (2) UC plus an automated population management tool (PMT), or (3) pharmacist-managed AMS care. Propensity scores and inverse probability of treatment weights (IPTWs) were estimated. Direct oral anticoagulant care models were first indirectly compared using warfarin as a common comparator within each region and then directly compared across regions.
MAIN OUTCOMES AND MEASURES
Patients were followed up until the first occurrence of an outcome (composite of thromboembolic stroke, intracranial hemorrhage, other major bleeding, or death), discontinuation of KP membership, or December 31, 2020.
RESULTS
Overall, 44 746 patients were included: 6182 in the UC care model (3297 DOAC; 2885 warfarin), 33 625 in the UC plus PMT care model (21 891 DOAC; 11 734 warfarin), and 4939 in the AMS care model (2089 DOAC; 2850 warfarin). Baseline characteristics (mean [SD] age, 73.1 [10.6] years, 56.1% male, 67.2% non-Hispanic White, median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, female sex] score of 3 [IQR, 2-5]) were well balanced after IPTW. Over a median follow-up of 2 years, patients who received the UC plus PMT or AMS care model did not have significantly better outcomes than those who received UC. The incidence rate of the composite outcome was 5.4% per year for DOAC and 9.1% per year for warfarin for those in the UC group, 6.1% per year for DOAC and 10.5% per year for those in the UC plus PMT group, and 5.1% per year for DOAC and 8.0% per year for those in the AMS group. The IPTW-adjusted hazard ratios (HRs) for the composite outcome comparing DOAC vs warfarin were 0.91 (95% CI, 0.79-1.05) in the UC group, 0.85 (95% CI, 0.79-0.90) in the UC plus PMT group, and 0.84 (95% CI, 0.72-0.99) in the AMS group (P = .62 for heterogeneity across care models). When directly comparing patients receiving DOAC, the IPTW-adjusted HR was 1.06 (95% CI, 0.85-1.34) for the UC plus PMT group vs the UC group and 0.85 (95% CI, 0.71-1.02) for the AMS group vs the UC group.
CONCLUSIONS AND RELEVANCE
This cohort study did not find appreciably better outcomes for patients receiving DOAC who were managed by either a UC plus PMT or AMS care model compared with UC.
Topics: Humans; Male; Female; Adult; Aged; Atrial Fibrillation; Warfarin; Cohort Studies; Retrospective Studies; Anticoagulants; Stroke
PubMed: 37410461
DOI: 10.1001/jamanetworkopen.2023.21971 -
Angiogenesis Aug 2023Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by small, dilated clustered vessels (telangiectasias) and by larger...
Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by small, dilated clustered vessels (telangiectasias) and by larger visceral arteriovenous malformations (AVMs), which directly connect the feeding arteries with the draining veins. These lesions are fragile, prone to rupture, and lead to recurrent epistaxis and/or internal hemorrhage among other complications. Germline heterozygous loss-of-function (LOF) mutations in Bone Morphogenic Protein 9 (BMP9) and BMP10 signaling pathway genes (endoglin-ENG, activin like kinase 1 ACVRL1 aka ALK1, and SMAD4) cause different subtypes of HHT (HHT1, HHT2 and HHT-juvenile polyposis (JP)) and have a worldwide combined incidence of about 1:5000. Expert clinicians and international scientists gathered in Cascais, Portugal from September 29th to October 2, 2022 to present the latest scientific research in the HHT field and novel treatment strategies for people living with HHT. During the largest HHT scientific conference yet, participants included 293 in person and 46 virtually. An impressive 209 abstracts were accepted to the meeting and 59 were selected for oral presentations. The remaining 150 abstracts were presented during judged poster sessions. This review article summarizes the basic and clinical abstracts selected as oral presentations with their new observations and discoveries as well as surrounding discussion and debate. Two discussion-based workshops were also held during the conference, each focusing on mechanisms and clinical perspectives in either AVM formation and progression or current and future therapies for HHT. Our hope is that this paper will represent the current progress and the remaining unanswered questions surrounding HHT, in order to serve as an update for those within the field and an invitation to those scientists and clinicians as yet outside of the field of HHT.
Topics: Humans; Activin Receptors, Type II; Arteriovenous Malformations; Bone Morphogenetic Proteins; Mutation; Signal Transduction; Telangiectasia, Hereditary Hemorrhagic
PubMed: 37695357
DOI: 10.1007/s10456-023-09886-5 -
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 -
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 -
Journal of Clinical Medicine Sep 2023It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE)... (Review)
Review
It is well established that direct oral anticoagulants (DOACs) are the cornerstone of anticoagulant strategy in atrial fibrillation (AF) and venous thromboembolism (VTE) and should be preferred over vitamin K antagonists (VKAs) since they are superior or non-inferior to VKAs in reducing thromboembolic risk and are associated with a lower risk of intracranial hemorrhage (IH). In addition, many factors, such as fewer pharmacokinetic interactions and less need for monitoring, contribute to the favor of this therapeutic strategy. Although DOACs represent a more suitable option, several issues should be considered in clinical practice, including drug-drug interactions (DDIs), switching to other antithrombotic therapies, preprocedural and postprocedural periods, and the use in patients with chronic renal and liver failure and in those with cancer. Furthermore, adherence to DOACs appears to remain suboptimal. This narrative review aims to provide a practical guide for DOAC prescription and address challenging scenarios.
PubMed: 37762897
DOI: 10.3390/jcm12185955