Long-term Oral Anticoagulant Therapy Research Articles

Extensive Left Sided Venous Thrombi and Bilateral Pulmonary Emboli in the Context of May-Thurner Syndrome for a Patient Presenting with Acute Flank Pain: A Case Report

May-Thurner syndrome is an underappreciated differential in the context of deep venous thrombosis. It is a symptomatic congenital abnormality resulting from compression of the left common iliac vein, sometimes also referred to as iliac vein compression syndrome in the literature. This case reports the presentation of a female with acute flank pain to the emergency department following a recent laparotomy for a complicated tubo-ovarian abscess. She was subsequently diagnosed with a sub-acute thrombus extending from the left common femoral vein into the left inferior vena cava, as well as new bilateral pulmonary emboli. As the patient had relative contraindications to thrombolysis, a shared decision was made with the vascular team to opt for conservative management only. In this instance, this included long-term oral anticoagulant therapy and compression stockings. This case asserts that clinicians should maintain a high index of suspicion for May-Thurner syndrome in the context of extensive left-sided thrombus formation.

Anesthetic Choice for Percutaneous Transcatheter Closure of the Left Atrial Appendage: A National Anesthesia Clinical Outcomes Registry Analysis.

Left atrial appendage closure (LAAC) was developed as a novel stroke prevention alternative for patients with atrial fibrillation, particularly for those not suitable for long-term oral anticoagulant therapy. Traditionally, general anesthesia (GA) has been more commonly used primarily due to the necessity of transesophageal echocardiography. Compare trends of monitored anesthesia care (MAC) versus GA for percutaneous transcatheter LAAC with endocardial implant and assess for independent variables associated with primary anesthetic choice. Multi-institutional data collected from across the United States using the National Anesthesia Clinical Outcomes Registry. Retrospective data analysis from 2017-2021. Independent-sample t tests or Mann-Whitney U tests were used for continuous variables and Chi-square tests or Fisher's exact test for categorical variables. Multivariate logistic regression was used to assess patient and hospital characteristics. A total of 19,395 patients underwent the procedure, and 352 patients (1.8%) received MAC. MAC usage trended upward from 2017-2021 (P < 0.0001). MAC patients were more likely to have an American Society of Anesthesiologists (ASA) physical status of≥ 4 (33.6% vs 22.89%) and to have been treated at centers in the South (67.7% vs 44.2%), in rural locations (71% vs 39.5%), and with lower median annual percutaneous transcatheter LAAC volume (102 vs 153 procedures) (all P < 0.0001). In multivariate analysis, patients treated in the West had 85% lower odds of receiving MAC compared to those in the Northeast (AOR: 0.15; 95% CI 0.03-0.80, P = 0.0261). While GA is the most common anesthetic technique for percutaneous transcatheter closure of the left atrial appendage, a small, statistically significant increase in MAC occurred from 2017-2021. Anesthetic management for LAAC varies with geographic location.

Incidence and outcome of periinterventional atrial fibrillation in patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention

Abstract Background Peri-interventional atrial fibrillation (AF) may be detected in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Data on the thromboembolic risk and long-term clinical outcome in patients with AF limited to the peri-interventional period is scarce. Purpose To assess the incidence and impact on long-term clinical outcome of peri-interventional de-novo AF in STEMI patients. Methods and Results This retrospective single-center cohort study included all patients who underwent PCI between January 2016 and November 2020 (n=491) due to STEMI. Patients were stratified to three cohorts of AF status: Pre-existing AF: n=42 [8.6%], newly diagnosed peri-interventional AF: n=56 [11.4%] and no AF: n=393 [80.0%]. Patients with newly diagnosed peri-interventional AF as well as patients with pre-existing AF had in median a mild-moderately reduced left ventricular ejection fraction (LVEF), patients in sinus rhythm in median a normal LVEF. During the average follow-up time of 4.7 years (min. 2 years, max. 7 years) the rate for readmission for AF or occurrence of AF without hospital admission was increased in patients with peri-interventional de-novo AF or pre-existing AF (n=6 [10.7%], n=10 [23.8%]) compared to those in sinus rhythm n=22 [5.6%] (p&amp;lt;0,001) The occurrence of ischemic stroke was higher in patients with peri-interventional de-novo AF (n=2 [3.6%] or with pre-existing AF (n=2 [4.8%]) compared to those in sinus rhythm (n=6 [1.5%]. (p=0.256) The risk of cardiovascular death was significantly higher in patients with newly diagnosed peri- interventional AF compared to patients with pre-existing or no AF (n=13 [23.2%], n=5 [11.9%], n= 37 [9.4%]) (p=0.009). In the patient group with peri-interventional de-novo AF, only 25.0% (n=13) received long-term oral anticoagulation therapy (OAK). The rate of stroke in patients who received OAK after peri- interventional de-novo AF was 7.7% (n=1) compared to those without OAK 2.6% (n=1). Conclusion Peri-interventional AF is a frequent finding in STEMI patients undergoing primary PCI. Patients with peri-interventional AF had a significantly increased risk for an adverse cardiovascular outcome. Optimal secondary prophylactic measures appear mandatory in this patient population. The significance of long-term OAK therapy is to be determined.

Pulmonary embolism in cancer patients. Effectiveness of vitamin K antagonists and direct oral anticoagulants in long-term therapy.

Patients with cancer are prone to develop pulmonary embolism (PE) in the course of cancer-associated thrombosis. These patients have increased risk of both recurrent venous thromboembolism and major bleeding. Pulmonary embolism treatment in the cancer patient group is challenging. Selection of anticoagulants, duration of anticoagulation, decision of adjuvant therapy, and adjustment of the regimen in special situations are the major problems that need to be considered in the treatment of cancer-associated PE. Current first line treatment in long-term therapy following an episode of PE is low molecular weight heparin (LMWH), with direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) listed as viable alternatives. This study aims to explore long-term oral anticoagulation therapy for cancer patients. Both VKAs and DOACs are compared to LMWH, which serves as a gold standard in anticoagulation therapy for cancer patients and has proven to be effective.

Choosing Appropriate Candidates for Left Atrial Appendage Occlusion.

Atrial fibrillation (AF) is one the most prevalent arrhythmias globally and is associated with a significantly higher risk of morbidity and mortality, including an up to five-fold increase in risk of stroke. While oral anticoagulation therapy remains the standard approach for stroke prevention in nonvalvular AF, left atrial appendage occlusion (LAAO) has emerged as a viable alternative for patients who are intolerant to long-term oral anticoagulation therapy. However, selecting appropriate candidates for LAAO requires a comprehensive evaluation that considers various clinical factors, although this presents a challenge in clinical practice. This review aims to provide an overview of the current recommendations for patient selection in LAAO procedures and the key factors that need to be considered both before and after the procedure, as well as the ongoing advancements in this field that may facilitate the selection of patients for LAAO.

Anticoagulant therapy with apixaban based on a pharmacogenetic approach: a course to safety

For the past 60 years, vitamin K antagonists (VKAs) have been the main drugs used for long-term oral anticoagulant therapy. Because of the significant limitations of AVCs, direct-acting oral anticoagulants (DOAKs) have been developed over the past decade. DOAKs have a predictable pharmacokinetic profile and lack the disadvantages of vitamin K antagonists. Apixaban is an oral direct-acting factor Xa inhibitor used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and deep vein thrombosis. Despite the use of recommended dosages, some patients may still experience bleeding or lack the desired anticoagulant effect. With this in mind, it is critical to explore new uses for direct oral anticoagulants and to predict their dosage when used in monotherapy or in combination with other drugs. In addition, recent studies have documented individual variability in plasma POAC levels. DOAC pharmacogenetics is a relatively new area of research. There is a need to understand the role of pharmacogenetics in adapting anticoagulant therapy according to a patient’s genetic characteristics. In this scientific review of current data, we detail the pharmacokinetics and pharmacogenetics of apixaban as well as new data concerning the clinical characteristics that predetermine the necessary dosage and risk of adverse drug reactions (ADRs). Indeed, the results obtained to date from basic and clinical studies certainly indicate an undeniable influence of genomic changes on the pharmacokinetics of POACs.

Rationale and design of Non-antithrombotic Therapy After Transcatheter Aortic Valve Implantation (NAPT) Trial

BackgroundDespite the wide implementation of transcatheter aortic valve implantation (TAVI), the optimal antithrombotic therapy after TAVI has not been established yet. Owing to the accumulating evidence supporting the efficacy and safety of single antiplatelet therapy (SAPT) over dual antiplatelet therapy, the latest guideline recommends life-long SAPT. However, there is scarce evidence supporting SAPT compared with non-antithrombotic therapy. Given the vulnerability of patients undergoing TAVI in terms of high bleeding risk, the benefit of SAPT may be canceled out by its potential increased bleeding risk. Study design and objectivesNon-antithrombotic Therapy After Transcatheter Aortic Valve Implantation (NAPT) Trial is a prospective, randomized controlled, open-label blinded endpoint multicenter trial conducted in Japan, testing the non-inferiority of non-antithrombotic therapy compared with aspirin monotherapy in patients who underwent TAVI and had no indications for long-term oral anticoagulation therapy (OAC). Patients who successfully underwent trans-femoral TAVI for severe aortic stenosis with either balloon-expandable or self-expandable valves are eligible for inclusion. Key exclusion criteria are (i) occurrence of perioperative complications (ii) indications of taking antithrombotic drugs for other reasons; (iii) eGFR <30 ml/min/1.73 m2 or hemodialysis or peritoneal dialysis. A total of 360 patients will be randomized (1:1) to aspirin monotherapy vs. non-antithrombotic therapy. The primary outcome is a composite of all-cause mortality, myocardial infarction, stroke, and bleeding. All bleeding events based on the Valve Academic Research Consortium 3 are included as a component of the primary outcome. ConclusionThe NAPT trial will determine the non-inferiority of a non-antithrombotic therapy compared with aspirin monotherapy after TAVI.

1- or 3-Month DAPT in Patients With HBR With or Without Oral Anticoagulant Therapy After PCI

BackgroundThe optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients on long-term oral anticoagulation (OAC) therapy is still uncertain. ObjectivesThe aim of this analysis was to assess the effects of 1- vs 3-month DAPT in patients with and those without concomitant OAC included in the XIENCE Short DAPT program. MethodsThe XIENCE Short DAPT program enrolled patients with high bleeding risk who underwent successful PCI with a cobalt-chromium everolimus-eluting stent. DAPT was discontinued at 1 or 3 months in patients free from ischemic events and adherent to treatment. The effect of 1- vs 3-month DAPT was compared in patients with and those without OAC using propensity score stratification. The primary endpoint was all-cause death or any myocardial infarction (MI). The key secondary endpoint was Bleeding Academic Research Consortium (BARC) types 2 to 5 bleeding. Outcomes were assessed from 1 to 12 months after index PCI. ResultsAmong 3,364 event-free patients, 1,462 (43%) were on OAC. Among OAC patients, the risk for death or MI was similar between 1- and 3-month DAPT (7.4% vs 8.8%; adjusted HR: 0.74; 95% CI: 0.49-1.11; P = 0.139), whereas BARC types 2 to 5 bleeding was lower with 1-month DAPT (adjusted HR: 0.71; 95% CI: 0.51-0.99; P = 0.046). These effects were consistent in patients with and those without OAC (P for interaction = NS). ConclusionsBetween 1 and 12 months after PCI, 1-month compared with 3-month DAPT was associated with similar rates of all-cause death or MI and a reduced rate of BARC types 2 to 5 bleeding, irrespective of OAC treatment.

Clinical and pharmacological approaches to personalization of the prescription of oral anticoagulants: clinical cases

Anticoagulants play an important role in reducing complications and mortality associated with thromboembolic disease. For some time, vitamin K antagonists (VKAs) have been the main drugs used for long-term oral anticoagulant therapy, but because of the significant limitations of VKAs over the past decade, pharmacological research has led to the development of new direct acting oral anticoagulants (DOACs). Direct acting oral anticoagulants have a rapid onset of action with peak levels within 2–4 hours and a half-life of about 12 hours, which is much shorter than that of vitamin K antagonists, a more predictable anticoagulant effect, no need for dose selection, routine laboratory monitoring of pharmacodynamic effects, and a lower frequency of clinically significant drug-drug interactions compared with warfarin. But anticoagulants can still cause serious adverse drug reactions (ADRs) in the form of hemorrhagic complications in hospitalized patients, as confirmed in studies. Currently, clinicalpharmacological technologies of personalized medicine such as pharmacogenetic and pharmacokinetic studies are considered as promising approaches to improve the safety of modern pharmacotherapy, allowing the prediction and prevention of various ADRs. In addition, there are emerging studies showing the importance of genetic features of patients in relation to the metabolism of oral anticoagulants, as well as described clinical situations where different gene polymorphisms, could be responsible for changes in the pharmacokinetics of DOACs. This article reviews clinical cases in which pharmacogenetic testing and therapeutic drug monitoring are used to optimize the clinical efficacy and maximum safety of anticoagulant therapy with apixaban and rivaroxaban.

Antithrombotic Management in AF Patients Following Percutaneous Coronary Intervention: A European Perspective.

AF is a highly prevalent disease, often requiring long-term oral anticoagulation to prevent stroke or systemic embolism. Coronary artery disease, which is common among AF patients, is often referred for myocardial revascularisation by percutaneous coronary intervention (PCI), which requires dual antiplatelet therapy to minimise the risk of stent-related complications. The overlap of AF and PCI is a clinical conundrum, especially in the early post-procedural period, when both long-term oral anticoagulation and dual antiplatelet therapy are theoretically indicated as a triple antithrombotic therapy. However, stacking drugs is not a desirable option because of the increased bleeding risk. Several strategies have been investigated to mitigate this concern, including shortening triple antithrombotic therapy duration and switching to a dual antithrombotic regimen. This review analyses the mechanisms underlying thrombotic complications in AF-PCI, summarises evidence surrounding antithrombotic therapy regimens and reports and comments on the latest European guidelines.

524 SAFETY OF HAND-HELD ULTRASOUND GUIDANCE FOR JUGULAR RIGHT HEART CATHETERIZATION IN ANTICOAGULATED PATIENTS: A TERTIARY CARE CENTER RETROSPECTIVE STUDY

Abstract Background RHC is currently the gold standard in the assessment of diagnosis, prognostic evaluation, and decision-making of pulmonary hypertension patients. Internal jugular vein (IJV) access is the preferred option among the available vascular access routes in most of pulmonary hypertension centers; furthermore, ultrasound (US) guidance is strongly recommended for the IJV access (IA) since it reduces the number of access complications. Many patients requiring RHC are on long-term oral anticoagulant therapy. Continuation of direct oral anticoagulant (DOAC) has been shown to be safe in patients undergoing percutaneous coronary intervention (PCI) and cardiac implantable electronic device implantation (CIED). However only few data in the literature are available in the setting of RHC. Objectives To compare the feasibility and safety of ultrasound (US)-guided IJV access for RHC procedure in pulmonary hypertension's patients anticoagulated vs non-anticoagulated. Methods This is a retrospective observational single–center study, including a cohort of 114 consecutive patients undergoing RHC via IJV assess by US guidance RHC at our tertiary care center between February 2018 and February 2022. The primary outcome was a composite of general (defined as overall success rate, patient discomfort, syncope, mortality) and access site complications (defined as significant hematoma formation greater than 5 cm in diameter, thrombosis, embolism, arterial puncture, pneumothorax, haemotomediastinum and hydro mediastinum, subcutaneous emphysema and nerve injury) after adequate hemostasis, at the access site at 6-hour post procedure. Results Of the 114 patients, 50 (44%) were on anticoagulation and 64 (56%) were not. Mean age was 71 ± 13 and 59 ± 16 years, respectively. The main indication for anticoagulation was atrial fibrillation in 40 (80%) patients. 43 (86%) patients were on DOAC, only 7 (14%) on Warfarin. 13 patients were on single antiplatelet therapy and 8 were on double antiplatelet therapy. Mean INR value was 1.25 ± 0.33 in the anticoagulated population and 1.08 ± 0.11 in the non-anticoagulated one. HAS-BLED score was equal or greater than 3 in 29 (25%) patients. Indication for RHC was mainly confirmation of PH class I diagnosis (54% of patients). None of the patients enrolled developed general or access site complications, except for 1 (2%) non-anticoagulated patient who develop a significant hematoma (defined as &amp;gt;5 cm in diameter) at the puncture site. All patients underwent day-hospital regimen, were able to mobilize immediately following the procedure, and were discharged as planned at 6 hours. Conclusions To the best of our knowledge this is the first study in the literature supporting the feasibility and safety of US guided IJV approach to RHC in anticoagulated patients when compared to non-anticoagulated patients affected by pulmonary hypertension. Keywords: Right heart catheterization, catheterization, anticoagulation, internal jugular vein, US-guidance, access site complications

Long-term antithrombotic therapy after coronary artery bypass grafting in patients with preoperative atrial fibrillation. A nationwide observational study from the SWEDEHEART registry

To provide data guiding long-term antithrombotic therapy after coronary artery by-pass grafting (CABG) in patients with preoperative atrial fibrillation (AF). From the SWEDEHEART registry, we included all patients, between January 2006 and September 2016, with preoperative AF and CHA2DS2-VASC score ≥2, undergoing CABG. Based on dispensed prescriptions 12 to 18 months after CABG, patients were divided in 3 groups: use of platelet inhibitors (PI) only, oral anticoagulant (OAC) only or a combination of OAC+PI. Outcomes were: Major adverse cardiac and cerebrovascular events (MACCE, [all-cause death, myocardial infarction, or stroke]), net adverse clinical events (NACE, [MACCE or bleeding]) and the individual components of NACE. Inverse probability of treatment weighting was used to adjust for the non-randomized study design. Among 2,564 patients, 1,040 (41%) were treated with PI alone, 1,064 (41%) with OAC alone, and 460 (18%) with PI+OAC. Treatment with PI alone was associated with higher risk for MACCE (adjusted HR 1.43, 95% CI 1.09-1.88), driven by higher risk for stroke and MI, compared with OAC alone. Treatment with PI+OAC, was associated with higher risk for NACE (adjusted HR 1.40, 95% CI 1.06-1.85), driven by higher risk for bleeds, compared with OAC alone. In this real-world observational study, a high proportion of patients with AF, undergoing CABG, did not receive a long-term OAC therapy. Treatment with OAC alone was associated with a net clinical benefit, compared with PI alone or PI+OAC.

The influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification the IRIVASC-trial

Abstract Vitamin K antagonists (VKA) such as warfarin or phenprocoumon are the mainstay of therapy for patients with several specific indications for long-term oral anticoagulant therapy (OAT). Due to interferences with Matrix-Gla protein, an important vitamin K-dependent local calcification inhibitor in cardiovascular structures, VKAs are theoretically linked to the development of increased cardiovascular calcification (CVC). The IRIVASC trial was a multi-center, prospective, controlled, open, randomized, interventional clinical trial and included 192 patients with atrial fibrillation or pulmonary embolism and an indication for oral anticoagulation &amp;gt;12 months. In short, patients with an indication for OAT were randomized to receive either Rivaroxaban (n=96) or VKA (n=96) and followed up over 12 months. MultiSlice CT (MSCT) was performed at baseline and after 12-month follow up. The primary endpoint of the study was the progression of coronary artery and aortic valve (AV) calcification, as determined by MSCT (volume score). Baseline demographic and laboratory values were comparable between the VKA and the Rivaroxaban groups (median age 72 vs 68, 73.6 vs 69.9 male). The main indication for anticoagulation was AF (95.4% vs 96.6%) After 12-month follow-up complete data sets were available for 164 patients (86%) for coronary calcification and 67 patients for valvular calcification (per protocol analysis). Overall, we found no differences in the primary endpoints. Development of coronary artery calcification was similar within the 2 groups as evidenced by similar developments of the coronary agatston score (804.8±1062.3 vs 946.7±1024.4, p=0.38), the coronary volume score (571.9±855.6 ml vs 791.7±820.1 ml, p=0.359) and the coronary mass score (143.2±195.9 mg vs. 172.2±190.8 mg, p=0.335) after 12 month. Similarly, there was no difference in the development of aortic valve calcification (AV) (AV Agatston score 441.6±711.9 vs. 352.6±751.2, p=0.621. AV volume score 388.2±589.0 ml vs 354.3±654.3, ml p=0.824 and AV Mass Score 75.7±135.1 mg vs 60.2±122.9, p=0.626 mg) (Table 1). To our knowledge this is the first multicenter prospective, randomized trial to ever investigate the effects of VKA vs rivaroxaban treatment regarding the development of coronary and valvular calcification. Our findings are clinically relevant as VKA will remain the mainstay of treatment for several conditions including mechanical valve replacement or antiphospholipid syndrome and hence include patients at cardiovascular risk. Our data point towards a comparable risk of overt CVC progression as detectable by CT-scans in patients irrespective of VKA or NOAK treatment. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): BAYER GmBH

Anti-SARS-CoV-2 vaccination does not influence anticoagulation levels in stable long-term warfarin treatment.

Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, administration of the currently available vaccines has mostly been recommended for subjects at high risk, including elderly populations on long-term oral anticoagulation therapy (OAT) with warfarin. However, there is no clear evidence of the stability of the International Normalised Ratio (INR) after vaccine administration in those subjects on long-term OAT. The present study aimed to investigate the effects of COVID-19 vaccination on anticoagulation levels in patients on long-term OAT. INR values of patients on long-term OAT who had undergone anti-SARS-CoV-2 vaccination from January to June 2021 were monitored for a total of 90 days follow-up after the first vaccination dose. These were then compared with INR values before vaccination. The second dose, when required, was administered during follow-up. Inclusion criterion was stable long-term INR for at least 6 months before vaccination. Exclusion criteria were recent surgery, intercurrent diseases, or treatment with medication that could compromise findings in the 3 months before vaccination and during follow-up. No differences were observed in the anticoagulation levels before and after COVID-19 vaccination in any of the patients studied: mean INR values were 2.39 (range 2.20-2.63) before vaccination and 2.40 (range 2.16-2.76) after vaccination (p=0.5). There was no difference in anticoagulation levels in relation to age, sex, indication for OAT, or type of vaccine (p>0.5). No bleeding or thrombotic complications were documented during follow-up. These are the first data to be reported on anticoagulation levels in patients on stable OAT after COVID-19 vaccination. No influence on the quality of OAT was detected after the vaccination; no bleeding or thrombotic complications were recorded in the follow-up. No difference between the four available COVID vaccines was found. Dose adjustment was only required in a few cases, thus confirming the stability of anticoagulation levels.

Cost-Utility and Budget Impact Analysis of Implementing Anticoagulation Clinics and Point-of-Care Monitoring Devices in Anticoagulated Patients in Argentina.

BackgroundWorldwide, 1 % of the population receives anticoagulation therapy, with prevalence higher in older adults. Difficulties in the adequate management of these patients have led to the development of strategies focused on achieving therapeutic control and reducing adverse events with efficient use of resources.ObjectiveTo estimate the cost utility and budget impact on the Argentinean health system of implementation of anticoagulation clinics (ACs) (with and without use of point-of-care [POC] CoaguChek® devices [Roche Diagnostics International Ltd]) compared with the traditional laboratory method (non-AC settings) for the management of anticoagulated patients.MethodsFor the cost-utility analysis, a cohort-based state transition model was designed to compare costs and health outcomes of implementing ACs for outpatient management of anticoagulated patients. The budget impact analysis used an analytical model to estimate the differential costs of implementing an AC and the expected adverse events avoided, and the differential costs of an international normalized ratio (INR) determination using a POC device rather than a conventional laboratory.ResultsWe calculated the study outcomes for a cohort of 1000 patients. Considering a 5 % discount rate, the use of ACs generated 13.9 additional quality-adjusted life-years (0.014 per patient) and 12.5 additional life-years (0.013 per patient). Incremental cost-effectiveness ratios of AC implementation with and without the use of POC devices compared with the scenario without ACs were dominant in both cases. In the probabilistic sensitivity analysis, nearly all simulated results were cost effective (i.e., below the 1 or 3 gross domestic product per capita thresholds). Budget impact analysis results showed AC implementation generated savings from the first year of implementation, with savings of AR $265,325 by year 5. The addition of POC devices in the ACs also generated savings as early as the first year of implementation, with savings of AR $488,072 by year 5 (AR $488 per patient).ConclusionsAnticoagulation clinics are estimated to be cost effective and generate notable savings in the treatment of patients on long-term oral anticoagulant therapy when compared with non-AC settings. These savings are considerably higher when POC devices are added as part of the patient management, due to lower laboratory technician costs per INR determination.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41669-022-00352-4.

Management of edoxaban in patients undergoing multiple procedures: a subanalysis of the EMIT-AF/VTE program

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Background Patients with atrial fibrillation (AF) or venous thromboembolism (VTE) receiving long-term direct oral anticoagulant (DOAC) therapy undergo diagnostic or therapeutic procedures at a rate of approximately 10% annually. The prospective Global EMIT-AF/VTE program (Edoxaban Management in Diagnostic and Therapeutic Procedures; NCT02950168, NCT02951039) demonstrated that physician-guided periprocedural management of the DOAC edoxaban in these patients was associated with low bleeding and thromboembolic event rates. It is unclear whether the experience of a previous (index) procedure influences the periprocedural management of subsequent procedures. Purpose To analyze differences in periprocedural edoxaban management in patients on chronic anticoagulation therapy undergoing multiple diagnostic or therapeutic procedures. Methods Baseline characteristics were recorded in patients enrolled in the EMIT-AF/VTE program who underwent multiple procedures. Details of periprocedural edoxaban interruption were collected from patients who underwent two procedures of the same European Heart Rhythm Association (EHRA) bleeding risk level or procedural type. Only data from the index and second procedure of the same category were included in this analysis; procedures conducted less than 7 days apart were excluded. All analyses are exploratory and descriptive in nature. Results Among 227 patients who underwent multiple procedures, the most common types were vascular and gastrointestinal (GI) procedures. Patients had a mean ± standard deviation age of 72.1 ± 9.8 years, a CHA2DS2-VASc score of 3.2 ± 1.6, a HAS-BLED score of 1.9 ± 1.0, and were mostly male (67.0%). Patients who underwent low/minor risk procedures were less likely to undergo edoxaban interruption with their second procedure compared with their index procedure (Figure 1A), and the median interruption duration was shorter for the second procedure (Table 1). A second high risk procedure was associated with a higher rate of both pre- and postprocedural edoxaban interruption compared with a patient’s index procedure, but treatment resumed earlier (Figure 1B). Patients who underwent vascular procedures had a lower rate of pre- and postprocedural interruption and a shorter interruption time with their second procedure (Table 1). Conversely, patients who underwent GI procedures experienced pre- and postprocedural interruption more often for their second procedure. The median interruption duration was longer for GI procedures than for vascular procedures (Table 1). Conclusion Overall, periprocedural edoxaban interruption varied by procedural bleeding risk and type. Edoxaban interruption patterns differed between index and second procedures, indicating that periprocedural edoxaban management may be influenced by the experience of previous procedures.

Yield of Echocardiography in Ischemic Stroke and Patients With Transient Ischemic Attack With Established Indications for Long-Term Direct Oral Anticoagulant Therapy: A Cross-Sectional Diagnostic Cohort Study.

BackgroundWe aimed to determine the diagnostic yield of transthoracic (TTE) and transesophageal echocardiography (TEE) in patients with ischemic stroke and transient ischemic attack with established indications for direct oral anticoagulants before the index event.Methods and ResultsThis was a retrospective cohort study of consecutive patients with preceding established indications for long‐term therapeutic direct oral anticoagulants presenting to a single comprehensive stroke center with ischemic stroke or transient ischemic attack. Choice of echocardiography modality was based on expert recommendations. The primary outcome was a composite of prespecified management‐relevant high‐risk findings adjudicated by an expert panel, based on TTE and TEE reports according to evidence‐based recommendations. Explorative analyses were performed to identify biomarkers associated with the primary outcome. Of 424 patients included (median [interquartile range] age, 78 [70–84] years; 175 [41%] women; National Institutes of Health Stroke Scale, 4 [1–12]; 67% atrial fibrillation), 292 (69%) underwent echocardiography, while 132 (31%) did not. Modality was TTE in 191 (45%) and TEE in 101 (24%). Median time from index event to echocardiography was 2 (1–3) days. TTE identified 26 of 191 (14%) patients with 35 management‐relevant pathologies. TEE identified 16 of 101(16%) patients with 20 management‐relevant pathologies. Most management‐relevant findings represented indicated coronary artery disease and valvular pathologies. In a further 3 of 191 (2%) patients with TTE and 4 of 101 (4%) patients with TEE, other relevant findings were identified. Variables associated with management‐relevant high‐risk pathologies included more severe stroke, diabetes, and laboratory biomarkers (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide], C‐reactive protein, d‐dimer, and troponin levels).ConclusionsIn patients with established indications for long‐term direct oral anticoagulant therapy and stroke who received echocardiography, both TTE and TEE identified a relevant and similar proportion of management‐relevant high‐risk pathologies and predictive biomarkers could help to guide diagnostic workup in such patients.

ReducinG stroke by screening for UndiAgnosed atRial fibrillation in elderly inDividuals (GUARD-AF): Rationale and design of the GUARD-AF randomized trial of screening for atrial fibrillation with a 14-day patch-based continuous ECG monitor

BackgroundScreening for atrial fibrillation (AF) is attractive because AF independently raises the risk of ischemic stroke, this risk is largely reversible by long-term oral anticoagulant therapy (OAC), and many patients with AF remain undiagnosed and untreated. Recent trials of one-time brief screening for AF have not produced a significant increase in the proportion of patients diagnosed with AF. Trials of longer-term screening have demonstrated an increase in AF diagnoses, primarily paroxysmal AF. To date, however, no trials have demonstrated that screening for AF results in lower rates of stroke. Clinical practice guidelines conflict in their level of support for screening for AF. MethodsThe GUARD-AF individually randomized trial is designed to test whether screening for AF in individuals age 70 years or greater using a 2-week single-lead electrocardiographic patch monitor can identify patients with undiagnosed AF and lead to treatment with OAC, resulting in a reduced rate of stroke in the screened population. The trial's efficacy end point is hospitalization for stroke (either ischemic or hemorrhagic) and the trial's safety end point is hospitalization for a bleeding event. End points will be ascertained via Medicare claims or electronic health records at 2.5 years after study start. Enrollment is based in primary care practices and the OAC decision for screen-detected cases is left to the patient and their physician. The initial planned target sample size was 52,000, with 26,000 allocated to either screening or to usual care. ResultsTrial enrollment was severely hampered by the novel coronavirus disease 2019 (COVID-19) pandemic and stopped at a total enrollment of 11,931 participants. Of 5,965 randomized to the screening arm, 5,713 patients (96%) returned monitors with analyzable results. Incidence of screen-detected and clinically detected AF and associated stroke and bleeding outcomes will be ascertained. ConclusionsGUARD-AF is the largest AF screening randomized trial using a longer-term patch-based continuous electrocardiographic monitor. The results will contribute important information on the yield of patch-based AF screening, the “burden” of AF detected (percent time in AF, longest episode), and physicians’ OAC decisions as a function of AF burden. GUARD-AF's stroke and bleed results will contribute to pooled trial analyses of AF screening, thereby informing future studies and guidelines.

Influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism.

BackgroundVitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long‐term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla‐protein, an important vitamin K‐dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K‐dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT).MethodsThe influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial (NCT02066662) is a multicenter, prospective RCT with a two‐arm, open‐label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre‐existent coronary calcification. The development of CVC will be assessed by follow‐up CT at 12 and 24 months.ResultsIn total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years.

Abstract WP83: The Challenges Of Stroke Prevention Following Intracerebral Haemorrhage; A Qualitative Study Exploring Physicians’ Decision Making.

Introduction: Initiating long-term oral anticoagulation (OAC) therapy in intracerebral haemorrhage (ICH) survivors who have atrial fibrillation (AF) has clinical equipoise for stroke physicians internationally, given the lack of clinical trial evidence. Understanding how physicians make decisions about stroke prevention in these patients will support and improve current decision-making practice and inform future guidelines. Aim: To explore physicians’ decision-making around prescription of long-term OAC for stroke prevention in patients with AF following an ICH. Methods: Qualitative sub-study of the PREvention of STroke in Intracerebral haemorrhaGE survivors with Atrial Fibrillation (PRESTIGE-AF) trial [NCT NCT03996772]. Semi-structured interviews with data analysed using Framework analysis. Results: Twenty stroke physicians (women n = 6 (30%), consultant in stroke medicine n =10, head of stroke department n = 6, geriatrician working in stroke n = 2, residents in neurology n = 2) across five European countries (Spain, France, Germany, Austria, UK) participated. The overarching theme ‘Managing Uncertainty’ highlights the difficulties faced by physicians. It draws together three sub-themes: ‘Computing the risks’, focusing on how physicians weigh-up the risks and benefits of long-term OAC; ‘The patient perspective’, which considers patients’ experiences and preferences; ‘Making the decision together’, which focuses on issues of communication between physicians and patients. Conclusion: The need to balance risks/benefits in the absence of data from randomised controlled trials and the uncertainty surrounding long-term outcomes of OAC were key challenges for physicians. Physicians rely on past personal clinical experience and collegiate advice to aid decision making. Physicians strive to ensure that patients understand the decision-making process. Future practice should support physicians in communicating clinical uncertainty to patients and encourage patients and physicians to work together to understand individual patients’ needs. Funding: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 754517.