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European Stroke Journal Sep 2023Ischaemic stroke patients with atrial fibrillation (AF) are at high risk of stroke recurrence despite oral anticoagulation therapy. Patients with cardiovascular...
INTRODUCTION
Ischaemic stroke patients with atrial fibrillation (AF) are at high risk of stroke recurrence despite oral anticoagulation therapy. Patients with cardiovascular comorbidities may take both antiplatelet and oral anticoagulation therapy (OAC/AP). Our study aims to evaluate the safety and efficacy of OAC/AP therapy as secondary prevention in people with AF and ischaemic stroke.
PATIENTS AND METHODS
We performed a post-hoc analysis of pooled individual data from multicenter prospective cohort studies and compared outcomes in the OAC/AP cohort and patients on DOAC/VKA anticoagulation alone (OAC cohort). Primary outcome was a composite of ischaemic stroke, systemic embolism, intracranial bleeding, and major extracranial bleeding, while secondary outcomes were ischaemic and haemorrhagic events considered separately. A multivariable logistic regression analysis was performed to identify independent predictors for outcome events. To compare the risk of outcome events between the two cohorts, the relation between the survival function and the set of explanatory variables were calculated by Cox proportional hazard models and the results were reported as adjusted hazard ratios (HR). Finally another analysis was performed to compare the overall risk of outcome events in both OAC/AP and OAC cohorts after propensity score matching (PSM).
RESULTS
During a mean follow-up time of 7.5 ± 9.1 months (median follow-up time 3.5 months, interquartile range ±3), 2284 stroke patients were on oral anticoagulants and 215 were on combined therapy. The multivariable model demonstrated that the composite outcome is associated with age (OR: 1.03, 95% CI: 1.01-1.04 for each year increase) and concomitant antiplatelet therapy (OR: 2.2, 95% CI: 1.48-3.27), the ischaemic outcome with congestive heart failure (OR: 1.55, 95% CI: 1.02-2.36) and concomitant antiplatelet therapy (OR: 1.93, 95% CI: 1.19-3.13) and the haemorrhagic outcome with age (OR: 1.03, 95% CI: 1.01-1.06 for each year increase), alcoholism (OR: 2.15, 95% CI: 1.06-4.39) and concomitant antiplatelet therapy (OR: 2.22, 95% CI: 1.23-4.02). Cox regression demonstrated a higher rate of the composite outcome (hazard ratio of 1.93 [95% CI, 1.35-2.76]), ischaemic events (HR: 2.05 [95% CI: 1.45-2.87]) and bleeding outcomes (HR: 1.90 [95% CI, 1.06-3.40]) in OAC/AP cohort. After PSM analysis, the composite outcome remained more frequent in people treated with OAC + AP (RR: 1.70 [95% CI, 1.05-2.74]).
DISCUSSION
Secondary prevention with combination of oral anticoagulant and antiplatelet therapy after ischaemic stroke was associated with worse outcomes in our cohort.
CONCLUSION
Further research is needed to improve secondary prevention by investigating the mechanisms of recurrent ischaemic stroke in patients with atrial fibrillation.
Topics: Humans; Atrial Fibrillation; Stroke; Platelet Aggregation Inhibitors; Brain Ischemia; Prospective Studies; Anticoagulants; Hemorrhage; Cerebral Infarction; Ischemic Stroke
PubMed: 37458099
DOI: 10.1177/23969873231183211 -
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 -
Journal of Neurosurgery. Case Lessons Mar 2024Traumatic aneurysms are a rare sequela of nonaccidental head trauma in infants. The rate of nonaccidental trauma (NAT) in the pediatric population is increasing;...
BACKGROUND
Traumatic aneurysms are a rare sequela of nonaccidental head trauma in infants. The rate of nonaccidental trauma (NAT) in the pediatric population is increasing; therefore, traumatic aneurysms are an important consideration in the evaluation of pediatric patients with abusive head trauma.
OBSERVATIONS
A 24-day-old infant with no significant past medical or birth history presented with twitching and poor oral intake for 1 day. The patient was found to have bilateral subdural hematomas, multifocal contusions, and traumatic subarachnoid hemorrhage. NAT work-up was remarkable for a period of repeated and prolonged abuse. Magnetic resonance angiography revealed a right pericallosal traumatic aneurysm that was treated by means of coil and Onyx embolization.
LESSONS
Traumatic intracranial aneurysms are a rare but serious sequela of pediatric abusive trauma. Traumatic intracranial aneurysms should be considered in the setting of intracranial pathology associated with high-energy trauma. Despite new methods for the management of traumatic aneurysms, this pathology remains challenging to identify and treat, and the prognosis remains poor because of the diffuse injury often involved in these patients.
PubMed: 38467046
DOI: 10.3171/CASE23600 -
Neuro-oncology Aug 2023Patients with diffuse glioma are at high risk of developing venous thromboembolism (VTE) over the course of the disease, with up to 30% incidence in patients with...
Patients with diffuse glioma are at high risk of developing venous thromboembolism (VTE) over the course of the disease, with up to 30% incidence in patients with glioblastoma (GBM) and a lower but nonnegligible risk in lower-grade gliomas. Recent and ongoing efforts to identify clinical and laboratory biomarkers of patients at increased risk offer promise, but to date, there is no proven role for prophylaxis outside of the perioperative period. Emerging data suggest a higher risk of VTE in patients with isocitrate dehydrogenase (IDH) wild-type glioma and the potential mechanistic role of IDH mutation in the suppression of production of the procoagulants tissue factor and podoplanin. According to published guidelines, therapeutic anticoagulation with low molecular weight heparin (LMWH) or alternatively, direct oral anticoagulants (DOACs) in patients without increased risk of gastrointestinal or genitourinary bleeding is recommended for VTE treatment. Due to the elevated risk of intracranial hemorrhage (ICH) in GBM, anticoagulation treatment remains challenging and at times fraught. There are conflicting data on the risk of ICH with LMWH in patients with glioma; small retrospective studies suggest DOACs may convey lower ICH risk than LMWH. Investigational anticoagulants that prevent thrombosis without impairing hemostasis, such as factor XI inhibitors, may carry a better therapeutic index and are expected to enter clinical trials for cancer-associated thrombosis.
Topics: Humans; Heparin, Low-Molecular-Weight; Venous Thromboembolism; Retrospective Studies; Anticoagulants; Neoplasms; Glioma; Glioblastoma; Biology
PubMed: 37100086
DOI: 10.1093/neuonc/noad059 -
Hamostaseologie Dec 2023For life-threatening or uncontrollable bleeding in association with the thrombin inhibitor dabigatran, the monoclonal antibody fragment idarucizumab is available, and...
BACKGROUND
For life-threatening or uncontrollable bleeding in association with the thrombin inhibitor dabigatran, the monoclonal antibody fragment idarucizumab is available, and for bleeding in association with the direct factor Xa inhibitors rivaroxaban or apixaban, the modified recombinant FXa protein andexanet is available for reversal. These antidotes represent emergency drugs that are typically used only after performing guideline-compliant multimodal measures.
METHODS
An interdisciplinary group of experienced experts in the fields of angiology, hematology, internal medicine, clinical pharmacology, laboratory medicine, transfusion medicine, anesthesiology, intensive care, and hemostaseology developed recommendations relevant to daily clinical practice based on the current scientific evidence.
RESULTS
Reversal of oral anticoagulants should be considered for severe bleeding in the following situations: (1) life-threatening bleeding or refractory hemorrhagic shock, (2) intracerebral bleeding, or (3) endoscopically unstoppable gastrointestinal bleeding. After successful hemostasis, anticoagulation (e.g., direct oral anticoagulant, vitamin K antagonist, and heparin) should be resumed promptly, taking into account individual bleeding and thromboembolic risk.
DISCUSSION
This article aims to facilitate the management of patients with andexanet by all medical disciplines involved, thereby ensuring optimal care of patients during bleeding episodes.
Topics: Humans; Anticoagulants; Hemorrhage; Rivaroxaban; Heparin; Recombinant Proteins; Factor Xa Inhibitors; Administration, Oral
PubMed: 37813368
DOI: 10.1055/a-2136-2391 -
Thrombosis and Haemostasis Aug 2023The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood...
The Fourth Maastricht Consensus Conference on Thrombosis included the following themes. Theme 1: The "coagulome" as a critical driver of cardiovascular disease. Blood coagulation proteins also play divergent roles in biology and pathophysiology, related to specific organs, including brain, heart, bone marrow, and kidney. Four investigators shared their views on these organ-specific topics. Theme 2: Novel mechanisms of thrombosis. Mechanisms linking factor XII to fibrin, including their structural and physical properties, contribute to thrombosis, which is also affected by variation in microbiome status. Virus infection-associated coagulopathies perturb the hemostatic balance resulting in thrombosis and/or bleeding. Theme 3: How to limit bleeding risks: insights from translational studies. This theme included state-of-the-art methodology for exploring the contribution of genetic determinants of a bleeding diathesis; determination of polymorphisms in genes that control the rate of metabolism by the liver of P2Y12 inhibitors, to improve safety of antithrombotic therapy. Novel reversal agents for direct oral anticoagulants are discussed. Theme 4: Hemostasis in extracorporeal systems: the value and limitations of ex vivo models. Perfusion flow chamber and nanotechnology developments are developed for studying bleeding and thrombosis tendencies. Vascularized organoids are utilized for disease modeling and drug development studies. Strategies for tackling extracorporeal membrane oxygenation-associated coagulopathy are discussed. Theme 5: Clinical dilemmas in thrombosis and antithrombotic management. Plenary presentations addressed controversial areas, i.e., thrombophilia testing, thrombosis risk assessment in hemophilia, novel antiplatelet strategies, and clinically tested factor XI(a) inhibitors, both possibly with reduced bleeding risk. Finally, COVID-19-associated coagulopathy is revisited.
Topics: Humans; Anticoagulants; COVID-19; Blood Coagulation; Thrombosis; Hemostasis; Blood Coagulation Disorders; Hemorrhage
PubMed: 36913975
DOI: 10.1055/a-2052-9175 -
Journal of the American Heart... Aug 2023Background Transcatheter closure of patent foramen ovale (PFO) has reduced the risk of recurrent stroke in patients with cryptogenic strokes in randomized clinical...
Background Transcatheter closure of patent foramen ovale (PFO) has reduced the risk of recurrent stroke in patients with cryptogenic strokes in randomized clinical trials. Whether PFO closure in clinical practice is associated with similar benefit remains unknown. Methods and Results We identified patients with PFO and a history of ischemic stroke or transient ischemic attack who were treated with PFO closure or medical therapy in the OptumLabs database. The primary end point was recurrent ischemic stroke or systemic embolization. Secondary outcomes included mortality, all stroke, transient ischemic attack, and major bleeding. A total of 6668 propensity-matched patients were included (PFO closure n=4111; medical therapy n=2557). The incidence of stroke or systemic embolization per 100 person-years was 2.38 after PFO cohort and 2.99 with medical therapy (hazard ratio [HR], 0.85 [95% CI, 0.68-1.05], =0.13). Mortality was lower in the PFO closure cohort (1.78 versus 2.59 per 100 person-years: HR, 0.69 [95% CI, 0.55-0.87], =0.002). Falsification end points showed that this difference is unlikely to be completely explained by residual confounders. There were no significant differences between the groups in secondary end points including intracranial hemorrhage and major bleeding except for an increase in nonintracranial hemorrhage bleeding among patients treated with oral anticoagulation (1.42 versus 2.16 per 100 person-years: HR, 0.69 [95% CI, 0.48-0.99], =0.043). The main end point was consistent in subanalyses including patients <60 years of age, patients with prior stroke, and those treated after the publication of the positive PFO trials in 2017. Conclusions In contemporary US practice, PFO closure is not associated with lower rates of recurrent ischemic stroke or systemic embolization compared with medical therapy. Potential reasons for this discrepancy warrant further investigation.
Topics: Humans; Ischemic Attack, Transient; Foramen Ovale, Patent; Neoplasm Recurrence, Local; Stroke; Hemorrhage; Ischemic Stroke; Secondary Prevention; Septal Occluder Device; Recurrence; Treatment Outcome
PubMed: 37489748
DOI: 10.1161/JAHA.123.030321 -
Journal of Clinical Medicine Dec 2023Atrial fibrillation (AF) is the most common sustained arrythmia and one of the strongest risk factors and causal mechanisms of ischemic stroke (IS). Acute IS due to AF... (Review)
Review
Atrial fibrillation (AF) is the most common sustained arrythmia and one of the strongest risk factors and causal mechanisms of ischemic stroke (IS). Acute IS due to AF tends to be more severe than with other etiology of IS and patients with treated AF have reported to experience worse outcomes after endovascular treatment compared with patients without AF. As cardioembolism accounts for more than a fifth of ISs and the risk of future stroke can be mitigated with effective anticoagulation, which has been shown to be effective and safe in patients with paroxysmal or sustained AF, the screening of patients with cryptogenic IS (CIS) for AF is paramount. Embolic stroke of undetermined source (ESUS) is a subtype of CIS with a high likelihood of cardioembolism. The European Stroke Organization and European Society of Cardiology guidelines recommend at least 72 h of screening when AF is suspected. The longer the screening and the earlier the time point after acute IS, the more likely the AF paroxysm is found. Several methods are available for short-term screening of AF, including in-hospital monitoring and wearable electrocardiogram recorders for home monitoring. Implantable loop monitors provide an effective long-term method to screen patients with high risk of AF after IS and artificial intelligence and convolutional neural networks may enhance the efficacy of AF screening in the future. Direct oral anticoagulants (DOACs) are preferred over vitamin K antagonists in both primary and secondary prevention of IS in AF patients. Recent data from the randomized controlled trials (RCT) also suggest that early initiation of DOAC treatment after acute IS is safe compared to later initiation. Anticoagulation treatment may still predispose for intracranial bleeding, particularly among patients with prior cerebrovascular events. Left atrial appendix closure offers an optional treatment choice for patients with prior intracranial hemorrhage and may offer an alternative to oral anticoagulation even for patients with IS, but these indications await validation in ongoing RCTs. There are still controversies related to the association of found AF paroxysms in CIS patients with prolonged screening, pertaining to the optimal duration of screening and screening strategies with prolonged monitoring techniques in patients with ESUS. In this review, we summarize the current knowledge of epidemiology, screening, and prognosis in AF patients with stroke.
PubMed: 38202037
DOI: 10.3390/jcm13010030 -
American Heart Journal Oct 2023Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Percutaneous left atrial appendage (LAA) closure (LAAC) was developed as a nonpharmacologic alternative to oral anticoagulants (OACs) in patients with atrial fibrillation (AF) who are at an increased risk for stroke or systemic embolism. The Watchman device permanently seals off the LAA to prevent thrombi from escaping into the circulation. Previous randomized trials have established the safety and efficacy of LAAC compared to warfarin. However, direct OACs (DOACs) have become the preferred pharmacologic strategy for stroke prevention in patients with AF, and there is limited data comparing Watchman FLX to DOACs in a broad AF patient population. CHAMPION-AF is designed to prospectively determine whether LAAC with Watchman FLX is a reasonable first-line alternative to DOACs in patients with AF who are indicated for OAC therapy.
STUDY DESIGN
A total of 3,000 patients with a CHA2DS2-VASc score ≥2 (men) or ≥3 (women) were randomized to Watchman FLX or DOAC in a 1:1 allocation at 142 global clinical sites. Patients in the device arm were to be treated with DOAC and aspirin, DOAC alone, or DAPT for at least 3 months postimplant followed by aspirin or P2Y12 inhibitor for 1-year. Control patients were required to take an approved DOAC for the duration of the trial. Clinical follow-up visits are scheduled at 3- and 12-months, and then annually through 5 years; LAA imaging is required at 4 months in the device group. Two primary end points will be evaluated at 3 years: (1) composite of stroke (ischemic/hemorrhagic), cardiovascular death, and systemic embolism compared for noninferiority, and (2) nonprocedural bleeding (International Society on Thrombosis and Haemostasis [ISTH] major and clinically relevant nonmajor bleeding) tested for superiority in the device arm against DOACs. The third primary noninferiority end point is the composite of ischemic stroke and systemic embolism at 5 years. Secondary end points include 3- and 5-year rates of (1) ISTH-defined major bleeding and (2) the composite of cardiovascular death, all stroke, systemic embolism, and nonprocedural ISTH bleeding.
CONCLUSIONS
This study will prospectively evaluate whether LAAC with the Watchman FLX device is a reasonable alternative to DOACs in patients with AF.
CLINICAL TRIAL REGISTRATION
NCT04394546.
Topics: Male; Humans; Female; Atrial Fibrillation; Treatment Outcome; Follow-Up Studies; Atrial Appendage; Anticoagulants; Stroke; Hemorrhage; Aspirin; Embolism
PubMed: 37279840
DOI: 10.1016/j.ahj.2023.05.022