Direct Oral Anticoagulant Medications Research Articles

Trends in the Use of Medications for Secondary Ischemic Stroke Prevention in Denmark, 2005-2021.

Understanding trends in the use of medications for secondary stroke prevention is crucial for identifying areas for improvement in stroke care. We examined the use of lipid-lowering, antihypertensive, glucose-lowering, oral anticoagulant, and antiplatelet medications after ischemic stroke hospitalization, from 2005 to 2021. Using nationwide registries in Denmark, we identified a cohort of patients discharged from hospital with a first-time or recurrent ischemic stroke (N = 150,744). Stratified by calendar year, we ascertained the 180-day probability of filling a prescription for the abovementioned medications after discharge. We further assessed factors associated with medication use. From 2005 to 2021, lipid-lowering medication use increased from 58.3% to 82.0%; atorvastatin use rose from 2.1% to 64.8% and simvastatin use decreased from 55.7% to 8.6%. Antihypertensive medication use remained stable, at approximately 89%, and various antihypertensive classes were used comparably. Glucose-lowering medication use increased from 71.5% in 2005 to 84.1% in 2021, driven primarily by an increase in metformin use (from 28.0% to 59.5%). Use of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors continually increased (from 1.7% to 17.5% and from 0.5% to 17.3%, respectively) between 2015 and 2021. Anticoagulant medication use rose from 45.9% in 2005 to 87.0% in 2021, primarily because of increased use of direct oral anticoagulant medications starting around 2010 and a decline in warfarin use. Antiplatelet use remained consistently high, at approximately 95%. Trends were consistent across subgroups of interest; however, overall medication use was lower in older patients (65 years and older), patients with severe stroke, and patients with neurologic and psychiatric comorbidities. Despite increasing trends in the use of 3 of 5 medication classes, the overall use of lipid-lowering, glucose-lowering, and oral anticoagulant medications was somewhat lower than expected according to clinical guidelines, particularly among older patients with more severe stroke and other comorbidities. The relatively low use in these subgroups may signify appropriate clinical decision making in consideration of frequent contraindications and reduced life expectancy or highlight potential areas of improvement for the care of patients with recent ischemic stroke.

The Impact of Clinical Pharmacy Services on Direct Oral Anticoagulant Medication Selection and Dosing in the Ambulatory Care Setting

Background: Off-label dosing of direct oral anticoagulants (DOACs) is both common and associated with adverse patient outcomes. Evidence describing best practices to support optimal direct oral anticoagulant (DOAC) dosing is limited. Objective: To describe the impact of clinical pharmacist intervention on DOAC prescribing. Methods: This retrospective study was a descriptive analysis conducted within an integrated healthcare system with a centralized, pharmacist-led Anticoagulation Management Service (AMS). Patients prescribed a DOAC between January 1, 2020 and December 31, 2020 were included. Pharmacy dispensing reports were generated for pharmacist review and anticoagulant drug therapy changes were recommended to physicians where appropriate. The primary objective was to describe the number and type of recommendations made. Secondary objectives were to determine the provider acceptance rate based on the intervention type and on clinical vs formulary recommendations. Results: Clinical pharmacists made 147 recommendations for 2331 unique patients included in the analysis. Twenty-three recommendations (16%) were to decrease the dose, 46 (31%) were to increase the dose, 14 (10%) were to change the medication due to clinical scenario, 62 (42%) were to change the medication due to cost, and 2 (1%) were another issue. One hundred twenty-three (84%) recommendations were accepted. The provider acceptance rate was similar for clinical and formulary recommendations (85% and 82% respectively). Conclusion: Implementation of report-driven clinical pharmacist intervention led to an improvement in appropriate DOAC medication selection and dosing.

Does early detection of atrial fibrillation reduce the risk of thromboembolic events? Rationale and design of the Heartline study

The impact of using direct-to-consumer wearable devices as a means to timely detect atrial fibrillation (AF) and to improve clinical outcomes is unknown. Heartline is a pragmatic, randomized, and decentralized application-based trial of US participants aged ≥65 years. Two randomized cohorts include adults with possession of an iPhone and without a history of AF and those with a diagnosis of AF taking a direct oral anticoagulant (DOAC) for ≥30 days. Participants within each cohort are randomized (3:1) to either a core digital engagement program (CDEP) via iPhone application (Heartline application) and an Apple Watch (Apple Watch Group) or CDEP alone (iPhone-only Group). The Apple Watch Group has the watch irregular rhythm notification (IRN) feature enabled and access to the ECG application on the Apple Watch. If an IRN notification is issued for suspected AF then the study application instructs participants in the Apple Watch Group to seek medical care. All participants were "watch-naïve" at time of enrollment and have an option to either buy or loan an Apple Watch as part of this study. The primary end point is time from randomization to clinical diagnosis of AF, with confirmation by health care claims. Key secondary endpoint are claims-based incidence of a 6-component composite cardiovascular/systemic embolism/mortality event, DOAC medication use and adherence, costs/health resource utilization, and frequency of hospitalizations for bleeding. All study assessments, including patient-reported outcomes, are conducted through the study application. The target study enrollment is approximately 28,000 participants in total; at time of manuscript submission, a total of 26,485 participants have been enrolled into the study. The Heartline Study will assess if an Apple Watch with the IRN and ECG application, along with application-facilitated digital health engagement modules, improves time to AF diagnosis and cardiovascular outcomes in a real-world environment. ClinicalTrials.gov Identifier: NCT04276441.

Nationwide Implementation of a Population Management Dashboard for Monitoring Direct Oral Anticoagulants: Insights From the Veterans Affairs Health System.

Direct oral anticoagulants are first-line therapy for common thrombotic conditions, including atrial fibrillation and venous thromboembolism. Despite their strong efficacy and safety profile, evidence-based prescribing can be challenging given differences in dosing based on indication, renal function, and drug-drug interactions. The Veterans Health Affairs developed and implemented a population management dashboard to support pharmacist review of anticoagulant prescribing. The dashboard includes information about direct oral anticoagulants and dose prescribed, renal function, age, and weight, potential interacting medications, and the need for direct oral anticoagulant medication refills. It is a stand-alone system. Using login data from the dashboard, nationwide implementation was evaluated using elements from the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. Between August 2016 and June 2020, 150/164 sites within the Veterans Health Affairs system used the dashboard, averaging 1875 patients per site. The dashboard was made available to sites on a staggered basis. Moderate or high adoption, defined as at least one login on at least 2 separate days per month, began slowly with 3/5 sites in the pilot phase but rapidly grew to 142/150 (94.7%) sites by June 2020. The average number of unique users per site increased from 2.4 to 7.5 over the study period. Moderate to high adoption of the dashboard's use was maintained for > 6 months in 126/150 (84.0%) sites by the end of the study period. There was rapid and sustained implementation and adoption of a population health dashboard for evidence-based anticoagulant prescribing across the national United States Veterans Health Administration health system. The impact of this tool on clinical outcomes and strategies to replicate this care model in other health systems will be important for broad dissemination and uptake.

Stroke Prevention in Cervical Artery Dissection.

Cervical artery dissection (CAD) is rare, yet it is a common cause of stroke in young and middle-aged adults. Historically, some senior clinicians favored anticoagulation in the prevention of stroke due to CAD. Choosing the optimal antithrombotic treatment with either antiplatelet (AP) or anticoagulant (AC) medications remains a challenge. This paper will review the clinical features and imaging of CAD, and the acute treatment and prevention of stroke due to CAD. Until 2015, there were no prospective randomized trials in the optimal antithrombotic management of CAD. The Cervical Artery Dissection in Stroke Study (CADISS) trial found that treatment with AC did not lower the risk of subsequent stroke or death at 3months when compared to AP agents. This led to a paradigm shift in national guidelines. In 2021, The Biomarkers and Antithrombotic Treatment in of Cervical Artery Dissection (TREAT-CAD) trial however did not confirm the non-inferiority of AP therapy in stroke prevention due to CAD. The optimal antithrombotic management for stroke prevention in CAD remains uncertain, while the superiority of anticoagulation has not been established, nor has the non-inferiority of AP agents. The future direction of research should consider early preventative treatment, dual treatment with AP agents, direct oral AC medications, and aggregation of data from existing randomized trials.

Women with atrial fibrillation in the Middle East: utilization of oral anticoagulant agents in a population with bad baseline clinical profiles and risk scores

Abstract Background Atrial fibrillation (AF) is the most common sustained arrhythmia in women and men worldwide and in the Middle East. Several studies have shown that women with AF are undertreated despite worse baseline clinical and risk profiles compared with men. It is largely unknown if this also applies to Middle Eastern AF patients. Purpose To evaluate baseline clinical features and utilization of guideline-recommended oral anticoagulant medications (OACs) in Middle Eastern women with AF. Methods The Jordan AF prospective multicenter study enrolled 2160 patients with AF, including 1164 (53.9%) women, in 20 hospital and outpatient clinics (May 2019 through January 2021). Results Nonvalvular AF was present in 1038 (91.0%) of women and 935 (94.6%) of men. Compared with men, women were older (mean age 69.2±11.5 years vs. 66.1±14.9 years, p<0.001), and had higher prevalence of hypertension (79.1% vs. 69.5%, p<0.001), diabetes (46.1% vs. 41.7%, p=0.04) and obesity (60.5% vs. 34.6%, p<0.001). Women, however, had lower prevalence of two comorbidities; heart failure (21.5% vs. 28.6, p=0.001) and coronary artery disease (7.7% vs. 15.4%, p<0.001) compared with men. Rate of utilization of oral anticoagulant agents (OACs) was higher in women than men with high and intermediate CHA2DS2 VASc scores (Table). Direct OACs were used in 64.0% of women and 63.3% of men with high risk score (p=NS). Multivariate analysis did not show sex to be an independent predictor of use of OACs. Conclusions Middle Eastern women with AF have worse baseline clinical and risk score profiles compared with men. In disagreement with other regional studies, the majority of these women received guideline-recommended OACs. Funding Acknowledgement Type of funding sources: None.

48 Management and Disposition of Patients with Venous Thromboembolism In Academic Vs. Rural Hospital Populations During the COVID-19 Pandemic

While being supported by national societies, management of low-risk venous thromboembolisms (VTEs) in the outpatient setting with direct oral anticoagulant medications (DOACs), has yet to become standard of care. We sought to determine the differences between rural and academic hospitals in VTE management and disposition of patients during the COVID pandemic.

Direct oral anticoagulants and cardiac surgery: A descriptive study of preoperative management and postoperative outcomes

ObjectiveRecommendations for perioperative management of direct oral anticoagulant (DOAC) treatment in cardiac surgery are lacking. To establish a standardized approach for these patients, we compared hemorrhagic complications and clinical outcomes in patients on DOAC medication, patients on vitamin K antagonists (VKA), and patients without preoperative anticoagulation. MethodsAll 3 groups underwent major cardiac surgery and were retrospectively analyzed: patients on DOAC were advised to take their last DOAC dose 4 days before hospital admission, and DOAC plasma levels were measured the day before surgery. In patients with plasma levels of >30 ng/mL, surgery was postponed until plasma level was below this threshold level. Postoperative chest tube drainage, bleeding complications, use of blood products, and thromboembolic events were collected for all groups. ResultsA total of 5439 patients no anticoagulation, 239 patients on VKA, and 487 patients on DOAC medication were included between April 2014 and July 2017. Adjusted postoperative chest tube drainage did not differ between the DOAC and VKA groups for the strategy applied in this study (380 mL/12 hours vs 360 mL/12 hours). Moreover, secondary endpoint measures, such as rethoracotomy (30 [6.16%] vs 15 [6.28%]), 30-day-mortality 12 [2.46%] vs 7 [2.93%]), blood-product use, and stroke, were not significantly different through implementation of our standardized study management (P > .05). ConclusionsOur standardized management for perioperative discontinuation of DOAC therapy may provide a safe approach to minimize hemorrhagic complications in cardiac surgery in patients on DOACs.

Reversing Direct Oral Anticoagulants in Acute Intracranial Hemorrhage.

Intracerebral hemorrhage is a major source of morbidity and mortality, accounting for 10% of all strokes. Oral anticoagulation therapy, while necessary to prevent thromboembolic complications, increases the risk of intracerebral hemorrhage and can potentially worsen bleeding in cases of acute hemorrhage. Before the introduction of direct oral anticoagulant agents in 2010, warfarin was the only option for oral anticoagulation. These new agents have an improved safety profile compared with warfarin but require different reversal strategies. Anticoagulation reversal in the setting of acute intracerebral hemorrhage is an evolving field. This article covers the most common direct oral anticoagulant medications, various available anticoagulant reversal strategies, and the latest guidelines for anticoagulation reversal in patients with acute intracranial hemorrhage.

Impact of Direct Oral Anticoagulants in Patients With Hip Fractures.

To assess the impact of direct oral anticoagulant (DOAC) intake compared with Coumadin (COU) in patients suffering hip fractures (HFs). Retrospective cohort analysis. Level 1 Trauma Center. Timing of surgical hip fixation. Three-hundred twenty patients 65 years of age or older with isolated HF were enrolled into the study: 207 (64.7%) without any antithrombotic therapy (no-ATT), 59 (18.4%) on COU, and 54 (16.9%) on DOACs. Time to surgery, blood loss, mortality, hospital length of stay, red blood cell transfusion, use of reversal agents, and Charlson Comorbidity Index. Patients on COU and DOACs had a higher Charlson Comorbidity Index compared with the no-ATT group (P < 0.0001). Despite the fact that significantly more patients received reversal agents in the COU group compared with DOAC medication (P < 0.0001), percentage of transfused patients were similar (54.2% vs. 53.7%). Time to surgery was significantly shorter in the no-ATT group when compared with DOAC patients (12-29.5 hours, respectively). No difference in postoperative hemorrhage, intensive care unit length of stay, and mortality was observed between groups. DOAC medication in HF patients caused long elapse time until surgical repair. We found no evidence of higher bleeding rates in HF patients on DOACs compared with COUs. Earlier HF fixation might be indicated in DOAC patients. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

373 Development of an Acute Deep Venous Thrombosis Clinical Pathway Using Apixaban May Safely Decrease Admission Rates and Improve Access to Care Regardless of Patient Socioeconomic Status

Outpatient management for patients presenting to the emergency department (ED) with acute deep venous thrombosis (DVT) has been shown to be safe. However, many patients have neither access to outpatient care nor can afford costly direct oral anticoagulant medications. We developed an ED clinical pathway which aims to improve access issues for all patients presenting with an acute DVT. This is the first such pathway which uses apixaban to these authors' knowledge. Objectives include safely decreasing hospital admissions; reducing downstream readmissions; and increasing outpatient follow-up. We developed an acute DVT clinical pathway. ED providers prescribed apixaban to patients eligible for discharge. ED pharmacists provided medication counseling and free 30-day vouchers. Case managers arranged outpatient appointments and provided financial aid guidance for apixaban treatment beyond 30 days for underinsured patients. For iliofemoral DVTs, interventional radiologists were consulted for consideration of intravascular therapy. ED providers were educated on the clinical pathway December 2016, and it was implemented January 2017. Charts were reviewed from 6 months pre- and post-implementation. Primary outcomes included discharge and outpatient follow-up rates. Secondary outcomes included repeat ED visit and hospitalization rates for DVT-related illness following discharge. Only patients with acute DVT diagnosed on formal Doppler ultrasound were included. Dichotomous variables were compared using the Fisher Exact Test. The following pathway was implemented 53 patients diagnosed with an acute DVT in the ED were reviewed from the 6 months before (n = 23) and after (n = 30) implementation of the pathway. Although no results reached statistical significance, all results were consistent with the hypotheses. After implementation, discharge rates increased from 39.1% (n=9) to 56.7% (n=17), (p=0.271). Discharged patients were more likely to follow up with a provider within 30 days or prior to readmission for DVT-related illness, 64.7% (n=11) versus 44% (n=4), (p=0.419). Post-discharge ED revisits and hospitalizations for a DVT-related illness decreased from 33% (n=3) to 17.6% (n=3), (p=0.628). No deaths were found at 90 days of those discharged from the ED in either group. We created an outpatient clinical pathway for patients diagnosed with acute DVT in the ED using apixaban regardless of socioeconomic status. Initial pilot data demonstrate nonsignificant trends towards decreased hospital admissions and improved follow-up without compromised patient safety. Given these pilot data, more highly powered research is necessary to fully identify the impact this pathway may have on patient outcomes and health care costs.

Should Adults With Mild Head Injury Who Are Receiving Direct Oral Anticoagulants Undergo Computed Tomography Scanning? A Systematic Review

Patients receiving direct oral anticoagulant medications commonly undergo computed tomography head scanning after mild traumatic brain injury, regardless of symptoms or signs. International guidelines have noted a lack of evidence to support management decisions for such patients. This systematic review aims to identify, appraise, and synthesize the current evidence for the risk of adverse outcome in patients receiving direct oral anticoagulants after mild head injury. A protocol was registered with PROSPERO and review methodology followed Cochrane Collaboration recommendations. Studies of adult patients with mild head injury (Glasgow Coma Scale score 13 to 15) and who were receiving direct oral anticoagulants that reported the risk of adverse outcome after the head injury were eligible for inclusion. A comprehensive range of bibliographic databases and gray literature was examined with a sensitive search strategy. Selection of eligible studies, data extraction, and risk of bias were evaluated independently by separate reviewers. A random-effects meta-analysis was used to provide a pooled estimate of the risk of adverse outcome. The overall quality of evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation Working Group approach. A total of 4,886 articles were screened for inclusion, of which 7 cohort studies including 346 patients met inclusion criteria. All studies were at high or unclear risk of bias as a result of selection and information bias. Estimates of adverse outcome (any death, intracranial hematoma, or neurosurgery) ranged from 0.0% to 8.3%. A random-effects meta-analysis showed a weighted composite outcome risk of 3.7% (95% confidence interval 1.7% to 5.8%; I2=3.3%). The overall quality of the body of evidence was low as a result of imprecision, indirectness, and risk of bias. There are limited data available to characterize the risk of adverse outcome in patients receiving direct oral anticoagulants after mild traumatic brain injury. A sufficiently powered prospective cohort study is required to validly define thisrisk, identify clinical features predictive of adverse outcome, and inform future head injury guidelines.

Reversal Strategies for Intracranial Hemorrhage Related to Direct Oral Anticoagulant Medications.

Direct oral anticoagulants (DOACs) are a new class of anticoagulants that directly inhibit either thrombin or factor Xa in the coagulation cascade. They are being increasingly used instead of warfarin or other vitamin K antagonists (VKAs). Adverse side effects of DOACs may result in hemorrhagic complications, including life-threatening intracranial hemorrhage (ICH), though to a much lesser degree than VKAs. Currently there are relatively limited indications for DOACS but their usage is certain to expand with the availability of their respective specific reversal agents. Currently, only idarucizumab (antidote for dabigatran) has been United States Food and Drug Administration- (FDA-) approved, but others (andexanet-α and ciraparantag) may be approved in near future, and the development and availability of such reversal agents have the potential to dramatically change the current anticoagulant use by providing reversal of multiple oral anticoagulants. Until all the DOACs have FDA-approved reversal agents, the treatment of the dreaded side effects of bleeding is challenging. This article is an attempt to provide an overview of the management of hemorrhage, especially ICH, related to DOAC use.

Taking Warfarin with Heparin Replacement and Direct Oral Anticoagulant Is a Risk Factor for Bleeding after Endoscopic Submucosal Dissection for Early Gastric Cancer

Background: Although bleeding after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) remains problematic, especially in patients taking anticoagulants, there are differing views on the ideal and optimal management for these patients. This study investigated the risk of bleeding after ESD in patients taking anticoagulants. Methods: We enrolled 61 consecutive patients taking anticoagulants (anticoagulant group) and 968 patients taking no antithrombotic agents (non-antithrombotic group) treated with ESD for EGC between December 2010 and October 2016. We analyzed the risk factors for bleeding after ESD in relation to the various clinical factors. Results: Incidences of bleeding after ESD were significantly higher (14%; 11/76) in the anticoagulant group compared to the non-antithrombotic group (3%; 40/1,167). Moreover, bleeding after ESD was significantly more common in patients in the warfarin monotherapy group (14%; 5/37) and in the direct oral anticoagulant (DOAC) monotherapy group (22%; 4/18), compared to the non-antithrombotic group. Multivariate analysis revealed that dialysis, the use of anticoagulants, and an operation time ≥75 min were independent risk factors for bleeding after ESD. Conclusions: Our data suggest that patients who take warfarin and receive heparin bridging, and those who take DOAC medication, are prone to bleeding after ESD for EGC.

A surgeon's guide to anticoagulant and antiplatelet medications part one: warfarin and new direct oral anticoagulant medications.

An increasing number of potent antiplatelet and anticoagulant medications are being used for the long-term management of cardiac, cerebrovascular, and peripheral vascular conditions. Management of these medications in the perioperative and peri-injury settings can be challenging for surgeons, mandating an understanding of these agents and the risks and benefits of various management strategies. In this two-part review, agents commonly encounter by surgeons in the perioperative and peri-injury settings are discussed and management strategies for patients on long-term antiplatelet and anticoagulant therapy reviewed. In part I, we review warfarin and the new direct oral anticoagulants. In part II, we review antiplatelet agents and assessment of platelet function and the perioperative management of long-term anticoagulant and antiplatelet therapy.

Ophthalmic Complications Associated with Direct Oral Anticoagulant Medications

ABSTRACTObjective: To describe the clinical features and management of six patients with ocular complications associated with direct oral anticoagulants (DOACs). Methods: The medical records of all adult patients known to be taking a DOAC and with an unusual bleeding event at a large tertiary referral center over a one-year period were reviewed. Patients with less than one-month follow-up were excluded. Data collection included relevant clinic notes, operative reports, surgical videos, and clinical images (fundus photography, optical coherence tomography, B-scan ultrasonography, and fluorescein angiography). Results: Six eyes in six patients were identified with an unusual bleeding event associated with DOAC use. One patient was taking apixaban, two patients were taking dabigatran, and three patients were taking rivaroxaban. Two patients had large submacular hemorrhage (including one with vitreous hemorrhage breakthrough), three patients had vitreous hemorrhage, and one patient had recurrent hyphema. Presenting visual acuity ranged from 20/40 to light perception. Three individuals required therapeutic and/or diagnostic pars plana vitrectomy for vitreous hemorrhage. Final visual acuity ranged from 20/25 to count finger vision. The associated DOAC was permanently discontinued in two of the six cases. Follow-up was one to four months from onset of identified DOAC-related complication. Conclusions: DOAC use may be associated with ocular bleeding. Ophthalmologists should be aware of potential hemorrhagic complications and obtain consultation with primary providers regarding DOAC cessation guidelines.

A Study of the Management of Patients Taking Novel Oral Antiplatelet or Direct Oral Anticoagulant Medication Undergoing Dental Surgery in a Rural Setting.

Purpose: Novel oral antiplatelet (NOAP) (prasugrel and ticagrelor) and direct oral anticoagulant drugs (DOAC) (dabigatran, rivaroxaban and apixaban) have emerged in the last decade. This study was undertaken to determine current approaches taken to the management of patients taking these agents in dental practice in a remote and rural setting. Methods: A small retrospective study was carried out in a small island population that identified patients taking one of the above drugs. All national health service and private dental records were examined to determine the type of treatment carried out and whether drug therapy, treatment plans or actual treatment were modified as a result of NOAP or DOAC therapy. In addition other outcomes such as referral to another service for advice or treatment and any adverse bleeding events were noted. Results: 156 dental encounters for 95 patients taking one of the drugs were identified. Significant events were identified in sixteen encounters and the management of patients taking each drug type differed significantly between cases but no patients returned with troublesome post-operative bleeding. Conclusions: The approaches taken by dental surgeons in Orkney in the management of the NOAPs and DOACs varied and this is likely to be a reflection of the limited literature available.