Warfarin In High-risk Patients Research Articles

Abstract P107: Trends In Oral Anticoagulation Therapy In Non-valvular Atrial Fibrillation Patients At High-risk Of Stroke After The 2019 AHA/ACC/HRS Update For The Management Of Patients With Atrial Fibrillation Guidelines

Background: Oral anticoagulation (OAC) reduces the risk of ischemic stroke in patients with atrial fibrillation (AF) but is underutilized in high-risk patients. We aimed to assess the impact of the 2019 guideline-recommended use of non-vitamin K OAC (NOACs) as first line therapy over warfarin for high-risk patients with non-valvular AF. Methods: Adult patients at Essentia Health with AF or atrial flutter on their problem list, seen in an ambulatory clinic between 7/1/2020-7/12/2021, were included in the baseline cohort. Patients were excluded if they had moderate to severe rheumatic mitral stenosis or mechanical heart valves, or were deceased or missing 1-year follow-up data. High-risk AF was defined as males with a CHA2DS2-VASc score ≥2 and females with a score ≥3. ATRIA bleed score was calculated using electronic health record data and divided into 3 groups: low-risk (0-3), intermediate (4) or high-risk (5-10). Patients were separated into three groups: warfarin, NOAC, or no OAC therapy. Results: Of the 12,014 patients in the baseline non-valvular AF registry, 8,032 were high-risk (mean age 75.9 ± 9.8 years, 57.5% male). Over half (57.1%, n=4619) were age ≥ 75 years and 63.4% (n=5095) were rural dwelling. Compared to baseline, at 1-year follow up, high-risk AF patients had similar use of any OAC (75.6%; n=6069 at baseline vs. 75.7%; n=6083 at 1-year follow-up). The use of warfarin decreased 2.3% [from 39.3% (n=3160) to 37.0% (n=2973), p <0.001] while NOAC use increased 2.4% [from 36.2% (n=2909) to 38.7% (n=3110; p <0.001]. Eliquis was the most prevalent NOAC prescribed (57.9%; n=1802). At 1-year follow-up, patients with high-risk AF and low-risk ATRIA bleed score, the use of any OAC therapy increased by 0.9% while those at high-risk AF and high-risk ATRIA bleed score, the use of any OAC therapy decreased 1%. In the multivariate logistical model, age, male sex, CHA2DS2-VASc score 4-6, hypertension, stroke/transient ischemic attack/thromboembolism, and cardiology visit within the last 3 years showed an increased association with prescription of any OAC (p<0.05). Vascular disease, high risk ATRIA bleed score, severe renal risk, prior hemorrhage, and left atrial appendage occlusion device (WATCHMAN) had a decreased odds of any OAC use (p<0.05). Conclusion: Implementation of the 2019 ACC/AHA/HRS guidelines that established NOACs as first line therapy over warfarin for non-valvular AF resulted in a slight increase in NOAC use and decrease in warfarin use in a large high-risk non-valvular AF population. Approximately one in four high risk patients with AF are not on any OAC therapy and may benefit from treatment to reduce thromboembolic risk.

Edoxaban versus Warfarin in high-risk patients with atrial fibrillation: A comprehensive analysis of high-risk subgroups

To compare the efficacy and safety of edoxaban vs warfarin in high-risk subgroups. ENGAGE AF-TIMI 48 was a multicenter randomized, double-blind, controlled trial in 21,105 patients with atrial fibrillation (AF) within 12 months and CHADS2 score >2 randomized to higher-dose edoxaban regimen (HDER) 60 mg/reduced 30 mg, lower-dose edoxaban regimen (LDER) 30 mg/reduced 15 mg, or warfarin, and followed for 2.8 years (median). The primary outcome for this analysis was the net clinical outcome (NCO), a composite of stroke/systemic embolism events, major bleeding, or death. Multivariable risk-stratification analysis was used to categorize patients by the number of high-risk features. The annualized NCO rates in the warfarin arm were highest in patients with malignancy (19.2%), increased fall risk (14.0%), and very-low body weight (13.5%). The NCO rates increased with the numbers of high-risk factors in the warfarin arm: 4.5%, 7.2%, 9.9% and 14.6% in patients with 0 to 1, 2, 3, and >4 risk factors, respectively (Ptrend <0.001). Versus warfarin, HDER was associated with significant reductions of NCO in most of the subgroups: elderly, patients with moderate renal dysfunction, prior stroke/TIA, of Asian race, very-low body weight, concomitant single antiplatelet therapy, and VKA-naïve. With more high-risk features (0->4+), the absolute risk reductions favoring edoxaban over warfarin increased: 0.3%->2.0% for HDER; 0.4%->3.4% for LDER vs warfarin (P = .065 and P < .001, respectively). While underuse of anticoagulation in high-risk patients with AF remains common, substitution of effective and safer alternatives to warfarin, such as edoxaban, represents an opportunity to improve clinical outcomes.

28-Year-Old Man With Recurrent Vertigo, Syncope, and Progressive Memory Impairment

28-Year-Old Man With Recurrent Vertigo, Syncope, and Progressive Memory Impairment

Stroke and Thromboprophylaxis in the Era of COVID-19

Stroke and Thromboprophylaxis in the Era of COVID-19

HEAVILY CALCIFIED CLOTS IN A PATIENT WITH CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION PRESENTING WITH BACTEREMIA

SESSION TITLE: Medical Student/Resident Pulmonary Vascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Antiphospholipid syndrome (APLS) is an autoimmune disorder that can lead to thrombotic disease. Here, we present a challenging case of catastrophic antiphospholipid syndrome with calcified clots, and chronic thromboembolic pulmonary hypertension (CTEPH) presenting with persistent bacteremia. CASE PRESENTATION: A 23-year-old female patient with a history of diabetes mellitus, methamphetamine and intravenous drug use disorder presented to an outside hospital with dry cough, shortness of breath, pleuritic chest pain, chills, and fatigue for 2 weeks. Blood cultures upon admission grew methicillin sensitive staphylococcus aureus (MSSA). Other labs were notable for thrombocytopenia and acute kidney injury. CT scan of chest and abdomen without contrast showed a large clot in her left pulmonary artery, inferior vena cava (IVC) extending into the right atrium (RA) with impressive calcifications (Figure 1). Transesophageal echocardiography showed no vegetations but revealed a large atrial thrombus extending from IVC into a dilated RA, dilated right ventricle, moderate tricuspid regurgitation with calculated right ventricular systolic pressure 55mmHg. Ventilation perfusion (VQ) scan showed a diffuse left lung perfusion defect without matched ventilation defect. She was transferred to our hospital for further care, her work-up revealed positive dilute Russell's viper venom time (dRVVT), cardiolipin antibodies and beta2-glycoprotein antibodies suggesting triple positive antiphospholipid syndrome. She was treated with intravenous heparin, however, developed hemoptysis requiring multiple blood transfusions and intubation, thus bronchial artery embolization was performed. Furthermore, she developed ST elevation myocardial infarction and splenic infarcts which were managed medically with resumption of heparin and antiplatelet therapy. She was eventually discharged on coumadin after completing six weeks of cefazolin and rifampin. DISCUSSION: This case illustrates an unusual presentation and calcification pattern of chronic clot, possibly due to the underlying infection, in a patient with CTEPH secondary to APLS. Mainstay of treatment for CTEPH remains anticoagulation followed by evaluation for pulmonary thromboendarterectomy (PTE) which is the only definite treatment (1). However, patients must tolerate anticoagulation, be clear of any infection and demonstrate adherence to therapy to undergo surgery. Furthermore, coumadin with an INR goal of 2.5 to 3.5 is recommended over direct oral anticoagulants in APLS with thromboembolism (2). CONCLUSIONS: In conclusion, CTEPH is associated with high morbidity and mortality, mainly from right heart failure (3). High level of suspicion is required to diagnose and promptly treat this rare disease with atypical presentation. Reference #1: Fedullo P, Kerr KM, Kim NH, Auger WR. Chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 2011; 183:1605. Reference #2: Pengo V, Denas G, Zoppellaro G, et al. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. 2018;132:1365–71. Reference #3: Hoeper MM, Mayer E, Simonneau G, Rubin LJ. Chronic thromboembolic pulmonary hypertension. Circulation 2006; 113:2011. DISCLOSURES: No relevant relationships by Timothy Fernandes, source=Web Response No relevant relationships by Abdurrahman Husain, source=Web Response No relevant relationships by Alexandra Rose, source=Web Response No relevant relationships by Qais Zawaydeh, source=Web Response

Prevention of venous thromboembolic events occurring in myeloma patients treated with second-generation novel agents.

Thrombosis and neoplasms are strictly linked, and the diagnosis of a malignancy is a relevant risk factor for venous thromboembolism (VTE). In particular, between gammopathies, the VTE risk is known to be increased in both monoclonal gammopathy of uncertain significance and in multiple myeloma, with a 3- and 9-fold increase respectively, when compared to the general population. The risk appears to be further increased in patients treated with immunomodulating drugs, such as thalidomide, especially when in combination with dexamethasone or conventional cytotoxic chemotherapies, and lenalidomide. In 2008 the International Myeloma Working Group put out thrombosis prophylaxis recommendations for myeloma patients treated with IMiDs. Current recommendations for thromboprophylaxis suggest the use of low-dose acetylsalicylic acid in patients with low risk for thrombosis and therapeutic dose anticoagulation with LMWH or warfarin for high-risk patients. However, these recommendations have been frequently not followed in the clinical practice, due to various reasons that involve the patients' will, the level of evidence of the recommendations and some selection biases in the studies that were taken as basis for writing down the indications. The new direct oral anticoagulants have been preliminarily evaluated for the prophylaxis of thrombotic events in IMiDs-treated myelomas, being promising, even if more expensive. Currently, the most reliable tool for a correct thrombotic risk stratification appears to be the complete clinical and anamnestic evaluation of the myeloma patients added to a strong physician awareness of the evidences that the literature contains until now.

Acute myocardial infarction, intraventricular thrombus and risk of systemic embolism.

The development of left ventricular thrombus (LVT) is a well-known and serious complication of acute myocardial infarction (AMI) due to the risk of systemic arterial embolism (SE), which is variable in its clinical picture and has potentially serious consequences depending on the extent of target organ damage. SE results in an increase in mortality and morbidity in these patients. LVT is one of the main causes of the development of ischaemic cardio-embolic cardiovascular events (CVE) after MI and the determination of the source of cardiac embolus is crucial for the initiation of adequate anticoagulant therapy in secondary prevention. Echocardiography holds an irreplaceable place in the diagnosis of LVT, contrast enhancement provides higher sensitivity. The gold standard for LVT diagnosis is cardiac magnetic resonance imaging, but it is not suitable as a basic screening test. In patients with already diagnosed LVT, it is necessary to adjust antithrombotic therapy by starting warfarin anticoagulation for at least 6 months with the need for echocardiographic follow-up to detect thrombotic residues. The effect of prophylactic administration of warfarin in high-risk patients after anterior AMI does not outweigh the risk of severe bleeding complications and does not result in a decrease in mortality and morbidity. At the present time, there is not enough evidence to use direct oral anticoagulants in this indication.

Antiphospholipid syndrome and direct oral anticoagulants: to the future and back again?

Antiphospholipid syndrome and direct oral anticoagulants: to the future and back again?

Rivaroxaban or Aspirin As Thromboprophylaxis in Multiple Myeloma

Hematological cancer has risk of venous thromboembolism of 28 fold compared to sex and age adjusted incidence in general population (JAMA 2005;293:715-722). This risk increases in patients with MM receiving dexamethasone and immunomodulatory drug. Thus, thromboprophylaxis with aspirin in low risk patients and LMWH or warfarin in high risk patients are recommended (Leukemia 2008;22:414-423). Direct oral anticoagulants are promising due to their convenience and costs-effectiveness in preventing VTE in other settings. They have not been extensively studied in myeloma therapy.From January of 2010 to December of 2017, 105 with MM received thalidomide and dexamethasone based triplet induction therapy, maintenance with thalidomide and creatinine clearance > 30 mL/min. From those, 23 (21.9%) had only an additional risk factor and were randomized 5:1 to receive 100 mg aspirin or 10 mg rivaroxaban until relapse and need another treatment. Doppler ultrasound was performed every six months or as medical indication in all patients and pulmonary CT scan if EP was suspected.Five patients received rivaroxaban, 3 males and 2 females, median age of 67.5 years; additional factors were obesity in 4 and DM in one. Aspirin was received by 18 patients, 10 males an 8 females, median age 66.8 years; additional factors were obesity in 10, DM in 5, erythropoietin in 3.No patient in the Rivaroxaban arm developed thrombosis; bleeding episodes were self-limited to the gums and easy bruising; no major bleeding was detected. One patient in the Aspirin arm, with body mass index of 31.22 kg/m2 as an additional risk factor, developed right iliofemoral DVT without PE; he was changed to rivaroxaban at therapeutic doses for six months with resolution of the DVT and then continue with 10 mg dose; bleeding episodes in all patients were similar to the rivaroxaban arm.In this small group of patients with a low risk factors with an additional one, that could be in an intermediate risk, the use of rivaroxaban showed a good efficiency and security profiles. Either, rivaroxaban or aspirin could be used in this situations and deserve further investigation. DisclosuresNo relevant conflicts of interest to declare.

Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome

Rivaroxaban is an effective and safe alternative to warfarin in patients with atrial fibrillation and venous thromboembolism. We tested the efficacy and safety of rivaroxaban compared with warfarin in high-risk patients with thrombotic antiphospholipid syndrome. This is a randomized open-label multicenter noninferiority study with blinded end point adjudication. Rivaroxaban, 20 mg once daily (15 mg once daily based on kidney function) was compared with warfarin (international normalized ratio target 2.5) for the prevention of thromboembolic events, major bleeding, and vascular death in patients with antiphospholipid syndrome. Only high-risk patients triple positive for lupus anticoagulant, anti-cardiolipin, and anti-β2-glycoprotein I antibodies of the same isotype (triple positivity) were included in the study. The trial was terminated prematurely after the enrollment of 120 patients (59 randomized to rivaroxaban and 61 to warfarin) because of an excess of events among patients in the rivaroxaban arm. Mean follow-up was 569 days. There were 11 (19%) events in the rivaroxaban group, and 2 (3%) events in the warfarin group. Thromboembolic events occurred in 7 (12%) patients randomized to rivaroxaban (4 ischemic stroke and 3 myocardial infarction), whereas no event was recorded in those randomized to warfarin. Major bleeding occurred in 6 patients: 4 (7%) in the rivaroxaban group and 2 (3%) in the warfarin group. No death was reported. The use of rivaroxaban in high-risk patients with antiphospholipid syndrome was associated with an increased rate of events compared with warfarin, thus showing no benefit and excess risk. This trial was registered at www.clinicaltrials.gov as #NCT02157272.

Primary and key secondary results from the ROCKET AF trial, and their implications on clinical practice.

The safety and efficacy of the oral anticoagulant rivaroxaban were studied in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF trial). A number of subanalyses of the ROCKET AF trial have subsequently analyzed the use of rivaroxaban in special patient populations. The outcomes of the ROCKET AF trial were reviewed. The use of rivaroxaban in higher risk populations, as determined by the presence of co-morbidities included in the CHADS2 criteria, was analyzed. Requirements for dose adjustment in patients with renal impairment and in East Asian patients were described. Finally, clinical management challenges, including interruptions in therapy, drug discontinuation, management of bleeding events, drug interactions, and management of patients requiring cardioversion/ablation were reviewed. Rivaroxaban is efficacious in high-risk populations, including elderly patients, patients with diabetes, heart failure, history of stroke, prior myocardial infarction, or peripheral arterial disease (PAD). Patients with PAD have a higher risk of bleeding with rivaroxaban compared with warfarin. East Asian populations do not require a dose adjustment for rivaroxaban, while a reduced dose of 15 mg daily is required for patients with moderate renal impairment. Rivaroxaban remains effective with temporary interruptions in therapy and in patients requiring cardioversion/ablation. Rates of major bleeding and subsequent outcomes were similar in patients on warfarin and rivaroxaban, although rates of gastrointestinal bleeding were higher with rivaroxaban. Concurrent use of antiarrhythmic therapy was not associated with adverse outcomes. Rivaroxaban represents an efficacious alternative to warfarin in high-risk patients with AF. Dose adjustment is required for patients with moderate renal impairment. Rivaroxaban can be used safely in a number of challenging clinical management scenarios although the concurrent use of amiodarone requires more study.

Abstract 16402: Feasibility and Safety of Uninterrupted Rivaroxaban in Patients Undergoing Radiofrequency Ablation for Long Standing Persistent Atrial Fibrillation

Introduction: Periprocedural anticoagulation management is key to minimize bleeding and thromboembolic complications during and after radiofrequency catheter ablation. Uninterrupted strategies with warfarin in high risk patients have shown superiority over interrupted strategies. We sought to assess the safety and feasibility uninterrupted rivaroxaban during atrial fibrillation (AF) ablation in patients with long standing persistent atrial fibrillation. Methods: One hundred and ninety six (196) consecutive patients undergoing AF ablation with uninterrupted rivaroxaban (last dose taken with food the night before the procedure and the following dose taken the night of the procedure) were matched by age and sex with an equal number of patients undergoing AF ablation with uninterrupted warfarin on a “therapeutic range”. All patients underwent pulmonary vein antrum isolation and ablation of non pulmonary vein triggers as disclosed by isoproterenol challenge test. Results: Baseline characteristics and procedural variables were similar between groups. Mean INR in warfarin group was 2.2 ± 0.5. CHADS2 Score was ≥ 2 in 141 (72%) in the rivaroxaban group and 130 (66%) in the warfarin patients (p=0.20). One pericardial tamponade and one groin hematoma occurred in rivaroxaban group while 2 patients in warfarin group developed groin hematoma. One TIA with positive MRI was present in the rivaroxaban group. Conclusions: Uninterrupted rivaroxaban therapy appears to be as safe and efficacious as uninterrupted warfarin strategy in preventing bleeding and thromboembolic events in patients undergoing long standing persistent AF ablation.

Extended use of dabigatran no better than warfarin for high‐risk patients after VTE

Extended use of dabigatran no better than warfarin for high‐risk patients after VTE

New and Emerging Anticoagulant Therapy for Atrial Fibrillation and Acute Coronary Syndrome

Abstract Thrombosis is an underlying cause of many cardiovascular disorders, and generation of thrombi in the arterial circulation can lead to unstable angina, myocardial infarction, or ischemic stroke. Antithrombotic therapy is widely used, with proven benefit to prevent ischemic stroke and thromboembolic events in patients with atrial fibrillation (AF) or to prevent further ischemic complications in patients with acute coronary syndrome (ACS). Traditional anticoagulants (including unfractionated heparin, low-molecular-weight heparin, and warfarin) and antiplatelet agents (including aspirin, clopidogrel, and prasugrel) are typically used for these indications. Limitations to their use include variable pharmacokinetic and pharmacodynamic profiles, inability to inhibit fibrin-bound thrombin, risk of heparin-induced thrombocytopenia, delayed onset of action, numerous drug interactions, need for substantial laboratory monitoring and dosage titrations, hyporesponsiveness or resistance, hypersensitivity, adverse events, and bleeding. To overcome some of the limitations of traditional agents, new antithrombotic agents under development are highly selective for specific coagulation factors blocking the synthesis of thrombin. Clinicians must have an understanding of the new anticoagulants to aid in the selection of appropriate therapies for patients. We describe the most relevant phases II and III clinical trials that evaluated several recent emerging anticoagulant drugs for use in patients with AF or ACS. The advantages of many new agents include predictable pharmaco-dynamic response and pharmacokinetic parameters, allowing for fixed oral dosing with no need for laboratory monitoring. For patients with AF, dabigatran is already approved for the prevention of stroke and systemic embolism, rivaroxaban appears to be an effective alternative to warfarin in high-risk patients, and apixaban may also be an effective alternative to aspirin in patients unable to take warfarin. Otamixaban shows promise as an intravenous alternative for patients with ACS in the acute care setting. Likewise, rivaroxaban, dabigatran, and darexaban with or without dual antiplatelet therapy may be beneficial for secondary prevention of ischemic events in patients with ACS.

Understanding deep vein thrombosis

What we need is a safe alternative to warfarin for high-risk patients, says Dr Alison Glenesk.

Synthesis, antiplatelet and antithrombotic activities of new 2-substituted benzopyrano[4,3-d]pyrimidin-4-cycloamines and 4-amino/cycloamino-benzopyrano[4,3-d]pyrimidin-5-ones

Atherothrombotic coronary artery disease, associated with deep vein thrombosis, is one of the most common causes of death worldwide. Recently, antiplatelet combination therapy using agents with different mechanisms of action, such as aspirin, dipyridamole, and thienopyridines, seems to be an attractive preventive approach. Moreover, several large, randomized clinical trials support combination therapy with aspirin plus warfarin in high-risk patients with atherosclerotic heart disease. Our research on the benzopyrano[4,3-d]pyrimidine system gave rise to the synthesis of a large number of compounds endowed with in vitro anti-aggregating activity. Several SAR considerations suggest that the benzopyranopyrimidine system is an appropriate scaffold to obtain molecules that are able to act simultaneously in different pathways of aggregation. Now, we report the synthesis of new 2-substituted benzopyrano[4,3-d]pyrimidin-4-cycloamines and 4-amino/cycloamino-benzopyrano[4,3-d]pyrimidin-5-ones and the results of the pharmacological study on haemostasis. Some tested compounds showed a large-spectrum antiplatelet activity in vitro, and are more potent than aspirin as antithrombotics in vivo but, at variance with aspirin, they do not increase bleeding. This paper describes novel antithrombotic compounds with an interesting pharmacological profile and a potentially attractive benefit/risk ratio, with their mechanism of action generally, but not exclusively, dependent on antiplatelet activity, deserving further investigations.

Ximelagatran for stroke prevention in atrial fibrillation

For decades, warfarin has been the gold standard anticoagulant that is recommended in patients with atrial fibrillation for the prevention of stroke and systemic embolic events. However, warfarin therapy has several disadvantages; including significant risks of bleeding, a narrow therapeutic margin necessitating frequent monitoring and interactions with numerous drugs and foods. These limitations created a need for safer, more convenient alternative anticoagulants for stroke prevention. Ximelagatran (Exanta™, Astrazeneca) is a novel, oral direct thrombin inhibitor that inhibits the final step in the coagulation process, namely, the conversion of fibrinogen to insoluble fibrin by thrombin. It has a rapid onset of action, a relatively wide therapeutic margin and a low potential for food and drug interactions. In addition, it can be administered in a fixed dosage, which obviates the need for anticoagulation monitoring, thus simplifying treatment and improving compliance. The Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) program has been investigating the safety and efficacy of ximelagatran for the prevention of stroke in patients with AF. This report discusses the implications of the recently published Phase III trial, SPORTIF III, which evaluated the efficacy and safety of ximelagatran as compared with warfarin in high-risk patients with AF.