Clinical Care Pathway and Management of Major Bleeding Associated with Nonvitamin K Antagonist Oral Anticoagulants: A Modified Delphi Consensus from Saudi Arabia and UAE.

Background: The nonvitamin K antagonist oral anticoagulants (NOACs) have become the mainstay anticoagulation therapy for patients requiring oral anticoagulants (OACs) in the Gulf Council Cooperation (GCC) countries. The frequency of NOAC-associated major bleeding is expected to increase in the Emergency Department (ED). Nonetheless, we still lack local guidelines and recommendations for bleeding management in the region. The present Delphi-based consensus aims to establish a standardized and evidence-based clinical care pathway for managing NOAC-associated major bleeding in the Kingdom of Saudi Arabia (KSA) and the United Arab Emirates (UAE). Methods: We adopted a three-step modified Delphi method to develop evidence-based recommendations through two voting rounds and an advisory meeting between the two rounds. A panel of 11 experts from the KSA and UAE participated in the consensus development. Results: Twenty-eight statements reached the consensus level. These statements addressed key aspects of managing major bleeding events associated with NOACs, including the increased use of NOAC in clinical practice, clinical care pathways, and treatment options. Conclusion: The present Delphi consensus provides evidence-based recommendations and protocols for the management of NOAC-associated bleeding in the region. Patients with major DOAC-induced bleeding should be referred to a well-equipped ED with standardized management protocols. A multidisciplinary approach is recommended for establishing the association between NOAC use and major bleeding. Treating physicians should have prompt access to specific reversal agents to optimize patient outcomes. Real-world evidence and national guidelines are needed to aid all stakeholders involved in NOAC-induced bleeding management.

Stroke and high-risk TIA outcomes with reduction of treatment duration when treatment initiated in emergency rooms (SHORTER-study).

BACKGROUND: Following transient ischemic attack (TIA) and minor stroke, the risk of recurrent stroke can be significantly reduced with short-duration dual antiplatelet therapy (DAPT). We wish to investigate whether 10 days of DAPT is as effective as 21 days' treatment. STUDY DESIGN: This is an open-label, randomized, parallel-group study comparing whether 10 days of DAPT treatment (ASA + clopidogrel) is non-inferior to 21 days of DAPT in patients with acute ischemic stroke (AIS) or high-risk TIA. In both groups, DAPT is started within 24 hours of symptom onset. This study is being conducted in approximately 15 study sites in the Kingdom of Saudi Arabia. The planned sample size is 1932. OUTCOMES: Non-inferiority of 10 days compared to 21 days of DAPT in the prevention of the composite endpoint of stroke and death at 90 days in AIS/TIA patients. The primary safety outcome is major intra-cranial and systemic hemorrhage. STUDY PERIOD: Enrolment started in the second quarter of 2023, and the completion of the study is expected in the fourth quarter of 2025. DISCUSSION: The trial is expected to show that 10 days of DAPT is non-inferior for the prevention of early recurrence of vascular events in patients with high-risk TIAs and minor strokes.

Evidence-based Management of Major Bleeding in Patients Receiving Direct Oral Anticoagulants: An Updated Narrative Review on the Role of Specific Reversal Agents.

The indications of direct oral anticoagulants (DOACs) have expanded over the past 15 years. DOACs are effective and safe oral anticoagulants associated with lower bleeding risks and mortality than vitamin K antagonists. However, DOAC users are prone to a considerable bleeding risk, which can occur at critical sites or lead to severe life-threatening conditions. Recent statistics indicated that major bleeding occurs in up to 6.62 DOAC users per 100 treatment years. With the increased use of DOACs in clinical practice, DOAC-associated major bleeding is expected to be encountered more frequently in the emergency department. The current international guidelines recommend specific reversal agents for the management of DOAC users with severe bleeding to reverse the anticoagulant effect and restore normal hemostasis. An individualized assessment was incorporated in specific clinical situations to guide the decision pathway of major bleeding management. However, specific reversal agents are unavailable or have limited availability in many countries, which is expected to negatively impact the clinical outcomes of DOAC-associated major bleeding. Limited real-world evidence is available from these countries regarding the clinical outcomes of patients with DOAC-associated major bleeding. This narrative review provided an updated assessment of the evidence-based approaches for the management of major bleeding in DOAC users. We also explored the clinical outcomes of patients with major bleeding from clinical settings where specific reversal agents are unavailable.

Dural Arteriovenous Fistula Presenting as a Rapidly Progressive Thalamic Dementia: A Case Report.

Rapidly progressive dementia is an uncommon neurological presentation and usually needs extensive workup, especially for reversible causes. Dural arteriovenous fistula (DAVF) has been rarely reported as a cause of thalamic dementia, in which bilateral thalamic venous congestion and edema cause dementia that usually progresses rapidly. We present a case of a 45 years-old male who presented with rapidly progressive severe attention and memory impairment over one week. Initial work-up showed bilateral thalamic recent venous infarctions and edema. Extensive work-up revealed an intracranial DAVF with internal deep venous thrombosis. Management with endovascular treatment of DAVF followed by anticoagulation for venous thrombosis leads to improvement of the patient's clinical condition, particularly memory and attention. In conclusion, DAFV could present with thalamic rapidly progressive dementia due to bithalamic infarctions and edema. Early diagnosis and treatment will reverse the cause and improve the patient's general and cognitive conditions.

Spontaneous Vertebral Artery Dissection Is an Under-Recognized Cause of Stroke in Young Patients: Two Case Reports and Review.

Cervicocerebral artery dissection (CAD) is an important and under-recognized cause of strokes in young and middle-aged patients. Spontaneous vertebral artery dissection (VAD) is a rare condition that can potentially cause a stroke without any preceding trauma or other causes of dissection. VAD rarely simulates classical headache syndromes. In this report, we discuss two young patients who were initially misdiagnosed as cases of headache until they presented with ischemic events, and were eventually diagnosed with spontaneous VAD. Case 1 involves a 41-year-old male patient who presented with severe headache radiating to left posterior neck pain and dizziness. He was initially misdiagnosed as a case of cervicogenic headache. He was subsequently diagnosed with extracranial VAD complicated by a delayed embolic ischemic stroke. However, he made full recovery within the next few days. Case 2 pertains to a 33-year-old female patient who presented with right-sided headache mimicking migraine; later on, new neurological signs prompted a diagnosis of acute ischemic infarction as a complication of intracranial VAD. In conclusion, VAD should be seriously considered when dealing with patients complaining of the first attack of headache that mimics migraine or those with cervicogenic headaches, which fail to respond to the usual treatment. Moreover, posterior circulation stroke among young patients or stroke with pain in the head and neck should be investigated carefully with extensive neuroimaging. Finally, prompt and accurate diagnosis of VAD followed by proper treatment is crucial for good outcomes and will prevent disability or even fatal complications in patients.

Pulse-steroid therapy in a 37-year-old man with acute motor and sensory axonal neuropathy: A case report.

We report a case of 37-year-old man admitted with acute motor and sensory axonal neuropathy (AMSAN) which was treated with pulse-steroid therapy after the plasmapheresis and intravascular immunoglobulin. The improvement of the symptoms of AMSAN after pulse-steroid therapy may represent a therapeutic alternative for this variant of Guillain-Barré syndrome.

Effect of addition of clopidogrel to aspirin on subdural hematoma: meta-analysis of randomized clinical trials.

BACKGROUND: Clopidogrel combined with aspirin is routinely prescribed after coronary artery stenting, in patients with acute coronary syndromes, and recently to prevent stroke in patients with acute minor ischemic stroke and TIA. Subdural hematomas are an important complication of antithrombotic treatment, but the risk associated with clopidogrel plus aspirin has not been previously defined. PURPOSE: To quantify the risk of subdural hematoma associated with dual antiplatelet therapy with clopidogrel plus aspirin. METHODS: Randomized clinical trials comparing clopidogrel plus aspirin with aspirin alone were identified by searching the Cochrane Central Register of Controlled Trials from 1990 to 2014, and restricted to those with more than 7 days of treatment. Two reviewers independently extracted data about subdural hematomas. RESULTS: Of 24 randomized trials testing clopidogrel added to aspirin, results for subdural hematoma were available for 11 trials, of which eight did not identify any subdural hematomas. The three trials reporting subdural hematomas were double-blind and included patients with recent lacunar stroke, acute coronary syndromes or atrial fibrillation with a total of 23,136 patients (mean age 66 years) and reported 39 subdural hematomas during a mean follow-up 2.1 years per patient. Clopidogrel plus aspirin was associated with a significantly increased risk of subdural hematoma compared with aspirin alone (risk ratio 2.0, 95% CI 1.0, 3.8; P = 0.04; fixed effects model; I2 for heterogeneity of 0%, P = 0.51). The average absolute incidence of subdural hematoma averaged 1.1 (95% CI 0.7,1.6) per 1000 patient - years among those assigned clopidogrel plus aspirin in 11 randomized trials. CONCLUSIONS: The absolute rate of subdural hematoma during dual antiplatelet therapy is low, averaging 1.1 per 1000 patient-years. Chronic treatment with clopidogrel plus aspirin significantly increases the risk of subdural hematoma compared with aspirin alone.

Predictors of stroke recurrence in patients with recent lacunar stroke and response to interventions according to risk status: secondary prevention of small subcortical strokes trial.

BACKGROUND: Among participants in the Secondary Prevention of Small Subcortical Strokes randomized trial, we sought to identify patients with high versus low rates of recurrent ischemic stroke and to assess effects of aggressive blood pressure control and dual antiplatelet therapy according to risk status. METHODS: Multivariable analyses of 3020 participants with recent magnetic resonance imaging-defined lacunar strokes followed for a mean of 3.7 years with 243 recurrent ischemic strokes. RESULTS: Prior symptomatic lacunar stroke or transient ischemic attack (TIA) (hazard ratio [HR] 2.2, 95% confidence interval [CI] 1.6, 2.9), diabetes (HR 2.0, 95% CI 1.5, 2.5), black race (HR 1.7, 95% CI 1.3, 2.3), and male sex (HR 1.5, 95% CI 1.1, 1.9) were each independently predictive of recurrent ischemic stroke. Recurrent ischemic stroke occurred at a rate of 4.3% per year (95% CI 3.4, 5.5) in patients with prior symptomatic lacunar stroke or TIA (15% of the cohort), 3.1% per year (95% CI 2.6, 3.9) in those with more than 1 of the other 3 risk factors (27% of the cohort), and 1.3% per year (95% CI 1.0, 1.7) in those with 0-1 risk factors (58% of the cohort). There were no significant interactions between treatment effects and stroke risk status. CONCLUSIONS: In this large, carefully followed cohort of patients with recent lacunar stroke and aggressive blood pressure management, prior symptomatic lacunar ischemia, diabetes, black race, and male sex independently predicted ischemic stroke recurrence. The effects of blood pressure targets and dual antiplatelet therapy were similar across the spectrum of independent risk factors and recurrence risk.