ISTH guidelines for antithrombotic treatment in COVID-19.

Antithrombotic agents reduce risk of thromboembolism in severely ill patients. Patients with coronavirus disease 2019 (COVID-19) may realize additional benefits from heparins. Optimal dosing and timing of these treatments and benefits of other antithrombotic agents remain unclear. In October 2021, ISTH assembled an international panel of content experts, patient representatives, and a methodologist to develop recommendations on anticoagulants and antiplatelet agents for patients with COVID-19 in different clinical settings. We used the American College of Cardiology Foundation/American Heart Association methodology to assess level of evidence (LOE) and class of recommendation (COR). Only recommendations with LOE A or B were included. Panelists agreed on 12 recommendations: three for non-hospitalized, five for non-critically ill hospitalized, three for critically ill hospitalized, and one for post-discharge patients. Two recommendations were based on high-quality evidence, the remainder on moderate-quality evidence. Among non-critically ill patients hospitalized for COVID-19, the panel gave a strong recommendation (a) for use of prophylactic dose of low molecular weight heparin or unfractionated heparin (LMWH/UFH) (COR 1); (b) for select patients in this group, use of therapeutic dose LMWH/UFH in preference to prophylactic dose (COR 1); but (c) against the addition of an antiplatelet agent (COR 3). Weak recommendations favored (a) sulodexide in non-hospitalized patients, (b) adding an antiplatelet agent to prophylactic LMWH/UFH in select critically ill, and (c) prophylactic rivaroxaban for select patients after discharge (all COR 2b). Recommendations in this guideline are based on high-/moderate-quality evidence available through March 2022. Focused updates will incorporate future evidence supporting changes to these recommendations.

Adverse Events Associated With the Addition of Aspirin to Direct Oral Anticoagulant Therapy Without a Clear Indication.

Importance: It is unclear how many patients treated with a direct oral anticoagulant (DOAC) are using concomitant acetylsalicylic acid (ASA, or aspirin) and how this affects clinical outcomes. Objective: To evaluate the frequency and outcomes of prescription of concomitant ASA and DOAC therapy for patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE). Design, Setting, and Participants: This registry-based cohort study took place at 4 anticoagulation clinics in Michigan from January 2015 to December 2019. Eligible participants were adults undergoing treatment with a DOAC for AF or VTE, without a recent myocardial infarction (MI) or history of heart valve replacement, with at least 3 months of follow-up. Exposures: Use of ASA concomitant with DOAC therapy. Main Outcomes and Measures: Rates of bleeding (any, nonmajor, major), rates of thrombosis (stroke, VTE, MI), emergency department visits, hospitalizations, and death. Results: Of the study cohort of 3280 patients (1673 [51.0%] men; mean [SD] age 68.2 [13.3] years), 1107 (33.8%) patients without a clear indication for ASA were being treated with DOACs and ASA. Two propensity score-matched cohorts, each with 1047 patients, were analyzed (DOAC plus ASA and DOAC only). Patients were followed up for a mean (SD) of 20.9 (19.0) months. Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P = .01). Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P = .02) compared with DOAC monotherapy. Major bleeding rates were similar between the 2 cohorts. Thrombotic event rates were also similar between the cohorts (2.5 events vs 2.3 events per 100 patient years for patients treated with DOAC and ASA compared with DOAC monotherapy, P = .80). Patients were more often hospitalized while undergoing combination therapy (9.1 vs 6.5 admissions per 100 patient years, P = .02). Conclusion and Relevance: Nearly one-third of patients with AF and/or VTE who were treated with a DOAC received ASA without a clear indication. Compared with DOAC monotherapy, concurrent DOAC and ASA use was associated with increased bleeding and hospitalizations but similar observed thrombosis rate. Future research should identify and deprescribe ASA for patients when the risk exceeds the anticipated benefit.

Extended Venous Thromboembolism Prophylaxis in Medically Ill Patients: An NATF Anticoagulation Action Initiative.

Hospitalized patients with acute medical illnesses are at risk for venous thromboembolism (VTE) during and after a hospital stay. Risk factors include physical immobilization and underlying pathophysiologic processes that activate the coagulation pathway and are still present after discharge. Strategies for optimal pharmacologic VTE thromboprophylaxis are evolving, and recommendations for VTE prophylaxis can be further refined to protect high-risk patients after hospital discharge. An early study of extended VTE prophylaxis with a parenteral agent in medically ill patients yielded inconclusive results with regard to efficacy and bleeding. In the Acute Medically Ill VTE Prevention with Extended Duration Betrixaban (APEX) trial, extended use of betrixaban halved symptomatic VTE, decreased hospital readmission, and reduced stroke and major adverse cardiovascular events compared with standard enoxaparin prophylaxis. Based on findings from APEX, the Food and Drug Administration approved betrixaban in 2017 for extended VTE prophylaxis in acute medically ill patients. In the Reducing Post-Discharge Venous Thrombo-Embolism Risk (MARINER) study, extended use of rivaroxaban halved symptomatic VTE in high-risk medical patients compared with placebo. In 2019, rivaroxaban was approved for extended thromboprophylaxis in high-risk medical patients, thus making available a new strategy for in-hospital and post-discharge VTE prevention. To address the critical unmet need for VTE prophylaxis in medically ill patients at the time of hospital discharge, the North American Thrombosis Forum (NATF) is launching the Anticoagulation Action Initiative, a comprehensive consensus document that provides practical guidance and straightforward, patient-centered recommendations for VTE prevention during hospitalization and after discharge.

CMS hospital readmission reduction program and anticoagulants received following a total hip and knee arthroplasty discharge.

OBJECTIVES: To assess association between 30 day readmission rate and treatment received after total hip and knee arthroplasty (THA/TKA) discharge (rivaroxaban vs. warfarin or non-anticoagulant). To subsequently model impact of increasing rivaroxaban use on the Hospital Readmission Reduction Program (HRRP) penalty, which was imposed on hospitals with excess 30 day readmissions after hospitalizations for selected conditions, including THA/TKA. METHODS: The US Truven Health MarketScan Medicare Supplemental database from 1 July 2010 to 30 April 2015 was used. A retrospective claims analysis was conducted to assess the risk of all-cause 30 day readmission among patients receiving either rivaroxaban or warfarin, or no anticoagulation following THA/TKA discharge. Simulations were performed to estimate the impact of post-discharge treatment on the HRRP penalty. RESULTS: The risk-adjusted all-cause 30 day readmission rates were 1.21% (95% confidence interval [95% CI]: 0.94%-1.49%), 1.41% (95% CI: 1.19%-1.58%) and 1.95% (95% CI: 1.81%-2.11%) for rivaroxaban, warfarin and non-anticoagulant cohorts, respectively. Using these rates, simulations illustrated that when switching patients from warfarin or non-anticoagulant to rivaroxaban, annual penalty per hospital would be reduced up to 67% or 88%, respectively. CONCLUSIONS: Rivaroxaban treatment post-THA/TKA discharge reduced the risk of 30 day readmission compared to non-anticoagulants. Simulations illustrated that increasing rivaroxaban use could decrease the HRRP penalty.

Mind the gap: results of a multispecialty survey on coordination of care for peri-procedural anticoagulation.

To understand how physicians from various specialties perceive coordination of care when managing peri-procedural anticoagulation. Cross-sectional survey of cardiologists, gastroenterologists, and primary care physicians (PCPs) in an integrated health system (N = 251). The survey began with a vignette of a patient with atrial fibrillation co-managed by his PCP, cardiologist, and an anticoagulation clinic who must hold warfarin for a colonoscopy. Respondents' experiences and opinions around responsibilities and institutional support for managing peri-procedural anticoagulation were elicited using multiple choice questions. We examined differences in responses across specialties using Chi square analysis. The response rate was 51% (n = 127). 52% were PCPs, 28% cardiologists, and 21% gastroenterologists. Nearly half (47.2%) of respondents believed that the cardiologist should be primarily responsible for managing peri-procedural anticoagulation, while fewer identified the PCP (25.2%), anticoagulation clinic (21.3%), or gastroenterologist (6.3%; p = 0.09). Respondents across specialties had significantly different approaches to deciding how to manage the clinical case presented (p < 0.001). Most cardiologists (60.0%) would decide whether to offer bridging without consulting with other providers or clinical resources, while most PCPs would decide after consulting clinical resources (57.6%). Gastroenterologists would most often (46.2%) defer the decision to another provider. A majority of all three specialties agreed that their institution could do more to help manage peri-procedural anticoagulation, and there was broad support (88.1%) for anticoagulation clinics' managing all aspects of peri-procedural anticoagulation. Providers across specialties agree that their institution could do more to help manage peri-procedural anticoagulation, and overwhelmingly support anticoagulation clinics' taking responsibility.

Management of Elective Surgery and Emergent Bleeding with Direct Oral Anticoagulants.

PURPOSE OF REVIEW: The purpose of this review was to offer practical management strategies for when patients receiving direct oral anticoagulants require elective surgery or present with bleeding complications. RECENT FINDINGS: Clinical practice guidelines are now available on the timing of periprocedural interruption of treatment with the newer direct oral anticoagulants based on their pharmacodynamics and pharmacokinetics and based on findings from cohort studies and clinical trials. An antibody that reverses the effects of dabigatran is now available, and a factor Xa decoy is being developed as an antidote to apixaban, betrixaban, edoxaban, and rivaroxaban. The timing of interruption of direct oral anticoagulants for elective surgery is based on multiple factors, including pharmacologic properties and interactions, the patient's renal function, and the type of planned surgery. There is little role for low-molecular-weight heparin bridging. Idarucizumab is the treatment of choice for dabigatran-related life-threatening bleeding, while andexanet alfa is being developed to reverse factor Xa inhibitors.

Risk for Venous Thromboembolism Recurrence Among Rivaroxaban-treated Patients Who Continued Versus Discontinued Therapy: Analyses Among Patients with VTE.

PURPOSE: The EINSTEIN-Extension trial showed that an extended rivaroxaban treatment significantly reduced the risk for venous thromboembolic (VTE) recurrence. The present study assessed the risk for VTE recurrence and major bleeding associated with extended rivaroxaban treatment in a clinical practice setting among patients with VTE. METHODS: A retrospective study was conducted using claims data from February 2011 to April 2015. It included adult patients who initiated rivaroxaban therapy within 7 days after their first VTE and who continuously used rivaroxaban for at least 3 months (index date: end of initial 3-month treatment). Categorized into discontinued and continued cohorts, patients were followed up from the index date until the end of continuous treatment (continued cohort) or end of data or reinitiation of oral anticoagulant therapy (discontinued cohort). Using inverse probability of treatment weights controlling for confounders, adjusted Kaplan-Meier rates of recurrent VTE and major bleeding events were compared. FINDINGS: The analysis showed that, compared with the discontinued cohort (n = 1,536), the continued cohort (n = 5,933) had a significantly lower VTE recurrence rate after an additional 3 months (0.70% vs 1.70%), 6 months (1.41% vs 2.34%), 9 months (1.82% vs 3.01%), and 12 months (1.97% vs 3.01%) of treatment (all, p < 0.05). The difference in the cumulative event rates for major bleeding was not statistically significant. Similar results were obtained in an analysis among patients with VTE receiving rivaroxaban for ≥6 months. IMPLICATIONS: Our results suggest that, in clinical practice settings, patients with VTE who continued rivaroxaban therapy after the initial 3- or 6-month treatment period had a significantly lower risk for VTE recurrence without a statistically significant increased risk for major bleeding.

Preclinical and Clinical Data for Factor Xa and "Universal" Reversal Agents.

Oral Factor Xa (FXa) inhibitors, a growing class of direct-acting anticoagulants, are frequently used to prevent stroke and systemic embolism in patients with atrial fibrillation and to prevent and treat venous thromboembolism. These drugs reduce the risk of clotting at the expense of increasing the risk of bleeding, and currently they have no specific reversal agent. However, andexanet alfa, a recombinant modified FXa decoy molecule, is in a late-phase clinical trial in bleeding patients, and ciraparantag, a small molecule that appears to reverse many anticoagulants including the FXa inhibitors, is in development. This review summarizes the published data to date on both drugs, which have the potential to change the management approach to patients with FXa inhibitor-associated major hemorrhage.

Performance of new anticoagulants for thromboprophylaxis in patients undergoing hip and knee replacement surgery.

Venous thromboembolism (VTE) represents one of the most preventable complications that occur during hospitalization, and measurement of hospital-associated VTE is becoming a key component in hospital quality measures. Guidelines for the prevention of deep vein thrombosis and pulmonary embolism have been published by several organizations to guide quality of care; however, some of the guidelines are divergent in their recommendations. This disagreement among guidelines is most pronounced in patients undergoing major orthopedic surgery. The advent of newer anticoagulants, which are now approved or in late-phase development, have already had an effect on the guidelines and may also affect quality measures in the future. In this article, we review the burden of VTE in patients undergoing major orthopedic surgery, highlight the differences in the guidelines, and examine the new anticoagulants as they are related to VTE prophylaxis in this patient group.

Duration of anticoagulation treatment in patients with venous thromboembolism.

Deep vein thrombosis and pulmonary embolism are clinical manifestations of venous thromboembolism, and they necessitate anticoagulant therapy in most cases. The duration of treatment is predicated on a balance between the risk of recurrent disease and the risk of bleeding inherent to anticoagulant therapy. It is important that physicians are aware of evidence-based guidelines that can enhance decision-making discussions with patients about the risks and benefits of the different durations of treatment. Keeping patients well informed as they consider these difficult choices helps them assume responsibility and may improve compliance in accordance with the tenets of osteopathic principles of care.