Reperfusion therapies in patients with acute ischaemic stroke and atrial fibrillation: data on safety and effectiveness from a multi-centre cohort study.

BACKGROUND: Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies. METHODS: Data from two multicenter cohort studies (RAF and RAF-NOACs) on consecutive patients with AF and AIS were analyzed to compare patients treated and not treated with reperfusion therapies (IVT and/or EVT). Multivariable logistic regression analysis was performed to identify independent predictors for outcome events: 90-day good functional outcome and mortality. A propensity score matching (PSM) analysis compared treated and untreated patients. RESULTS: Overall, 441 (25.4%) were included in the reperfusion-treated group and 1,295 (74.6%) in the untreated group. The multivariable model suggested that reperfusion therapies were significantly associated with good functional outcome. Rates of mortality and disability were higher in patients not treated, especially in the case of higher NIHSS scores. In the PSM comparison, 173/250 patients (69.2%) who had received reperfusion therapies had good functional outcome at 90 days, compared to 146/250 (58.4%) untreated patients (p = 0.009, OR: 1.60, 95% CI:1.11-2.31). CONCLUSIONS: Patients with AF and AIS treated with reperfusion therapies had a significantly higher rate of good functional outcome and lower rates of mortality compared to those patients with AF and AIS who had undergone conservative treatment.

Identification of hemodynamically stable patients with acute pulmonary embolism at high risk for death: external validation of different models.

BACKGROUND: The optimal strategy for identification of hemodynamically stable patients with acute pulmonary embolism (PE) at risk for death and clinical deterioration remains undefined. OBJECTIVES: We aimed at assessing the performances of currently available models/scores for identifying hemodynamically stable patients with acute, symptomatic PE at risk of death and clinical deterioration. METHODS: Prospective multicentre cohort study including patients with acute PE (COPE, NCT03631810). Primary study outcome was in-hospital death within 30 days or clinical deterioration. Other outcomes were in-hospital death, death and PE-related death all at 30 days. We calculated positive and negative predictive values, c-statistics of ESC-2014, ESC-2019, PEITHO, Bova, TELOS, FAST and NEWS2 for the study outcomes. RESULTS: In 5,036 hemodynamically stable patients with acute PE, positive predictive values for the evaluated models/scores were all below 10%, except for TELOS and NEWS2; negative predictive values were above 98% for all the models/scores, except for FAST and NEWS-2. ESC-2014 and TELOS had good performances for in-hospital death or clinical deterioration (c-statistic 0.700 and 0.722, respectively), in-hospital death (c-statistic 0.713 and 0.723, respectively) and PE-related death (c-statistic 0.712 and 0.777, respectively); PEITHO, Bova and NEWS2 also had good performances for PE-related death (c-statistic 0.738, 0.741 and 0.742, respectively). CONCLUSION: In hemodynamically stable patients with acute PE, the accuracy for identification of hemodynamically stable patients at risk for death and clinical deterioration varies across the available models/scores; TELOS seems to have the best performances. These data can inform management studies and clinical practice.

Comparison of rivaroxaban and low molecular weight heparin in the treatment of cancer-associated venous thromboembolism: a Swedish national population-based register study.

BACKGROUND: Treating cancer-associated venous thromboembolism (CAT) with anticoagulation prevents recurrent venous thromboembolism (rVTE), but increases bleeding risk. OBJECTIVES: To compare incidence of rVTE, major bleeding, and all-cause mortality for rivaroxaban versus low molecular weight heparin (LMWH) in patients with CAT. METHODS: We developed a cohort study using Swedish national registers 2013-2019. Patients with CAT (venous thromboembolism within 6 months of cancer diagnosis) were included. Those with other indications or with high bleeding risk cancers were excluded (according to guidelines). Follow-up was from index-CAT until outcome, death, emigration, or end of study. Incidence rates (IR) per 1000 person-years with 95% confidence interval (CI) and propensity score overlap-weighted hazard ratios (HRs) for rivaroxaban versus LMWH were estimated. RESULTS: We included 283 patients on rivaroxaban and 5181 on LMWH. The IR for rVTE was 68.7 (95% CI 40.0-109.9) for rivaroxaban, compared with 91.6 (95% CI 81.9-102.0) for LMWH, with adjusted HR 0.77 (95% CI 0.43-1.35). The IR for major bleeding was 23.5 (95% CI 8.6-51.1) for rivaroxaban versus 49.2 (95% CI 42.3-56.9) for LMWH, with adjusted HR 0.62 (95% CI 0.26-1.49). The IR for all-cause mortality was 146.8 (95% CI 103.9-201.5) for rivaroxaban and 565.6 (95% CI 541.8-590.2) for LMWH with adjusted HR 0.48 (95% CI 0.34-0.67). CONCLUSIONS: Rivaroxaban performed similarly to LMWH for patients with CAT for rVTE and major bleeding. An all-cause mortality benefit was observed for rivaroxaban which potentially may be attributed to residual confounding. TRIAL REGISTRATION NUMBER: NCT05150938 (Registered 9 December 2021).

Direct Oral Anticoagulants for Pulmonary Embolism.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. For most patients, the standard of treatment has long consisted on low-molecular-weight heparin followed by vitamin K antagonists, but a number of clinical trials and, subsequently, post-marketing studies have shown that direct oral anticoagulants (DOACs) with or without lead-in heparin therapy are effective alternatives with fewer adverse effects. This evidence has led to important changes in the guidelines on the treatment of VTE, including pulmonary embolism (PE), with the DOACs being now recommended as the first therapeutic choice. Additional research has contributed to identifying low-risk PE patients who can benefit from outpatient management or from early discharge from the emergency department with DOAC treatment. There is evidence to support the use of DOACs in intermediate-risk PE patients as well as in high-risk patients receiving thrombolytic treatment. The use of DOACs has also been proven to be safe and effective in special populations of PE patients, such as patients with renal impairment, liver impairment, and cancer.

Comparison of Clinical Outcomes in Patients with Active Cancer Receiving Rivaroxaban or Low-Molecular-Weight Heparin: The OSCAR-UK Study.

BACKGROUND: In most patients with cancer-associated venous thromboembolism (CT), essentially those not at high risk of bleeding, guidelines recommend treatment with direct oral anticoagulants as an alternative to low-molecular-weight heparins (LMWHs). Population-based studies comparing these therapies are scarce. OBJECTIVES: To compare the risk of venous thromboembolism (VTE) recurrences, significant bleeding, and all-cause mortality in patients with CT receiving rivaroxaban or LMWHs. PATIENTS/METHODS: Using UK Clinical Practice Research Datalink data from 2013 to 2020, we generated a cohort of patients with first CT treated initially with either rivaroxaban or LMWH. Patients were observed 12 months for VTE recurrences, significant bleeds (major bleeds or clinically relevant nonmajor bleeding requiring hospitalization), and all-cause mortality. Overlap weighted sub-distribution hazard ratios (SHRs) compared rivaroxaban with LMWH in an intention-to-treat analysis. RESULTS: The cohort consisted of 2,259 patients with first CT, 314 receiving rivaroxaban, and 1,945 LMWH, mean age 72.4 and 66.9 years, respectively. In the 12-month observational period, 184 person-years following rivaroxaban and 1,057 following LMWH, 10 and 66 incident recurrent VTE events, 20 and 102 significant bleeds, and 10 and 133 deaths were observed in rivaroxaban and LMWH users, respectively. The weighted SHR at 12 months for VTE recurrences in rivaroxaban compared with LMWH were 0.80 (0.37-1.73); for significant bleeds 1.01 (0.57-1.81); and for all-cause mortality 0.49 (0.23-1.06). CONCLUSION: Patients with CT, not at high risk of bleeding, treated with either rivaroxaban or LMWH have comparable effectiveness and safety outcomes. This supports the recommendation that rivaroxaban is a reasonable alternative to LMWH for the treatment of CT.

Algorithm for Rapid Exclusion of Clinically Relevant Plasma Levels of Direct Oral Anticoagulants in Patients Using the DOAC Dipstick: An Expert Consensus Paper.

BACKGROUND: With the widespread use of direct oral anticoagulants (DOACs), there is an urgent need for a rapid assay to exclude clinically relevant plasma levels. Accurate and rapid determination of DOAC levels would guide medical decision-making to (1) determine the potential contribution of the DOAC to spontaneous or trauma-induced hemorrhage; (2) identify appropriate candidates for reversal, or (3) optimize the timing of urgent surgery or intervention. METHODS AND RESULTS: The DOAC Dipstick test uses a disposable strip to identify factor Xa- or thrombin inhibitors in a urine sample. Based on the results of a systematic literature search followed by an analysis of a simple pooling of five retrieved clinical studies, the test strip has a high sensitivity and an acceptably high negative predictive value when compared with levels measured with liquid chromatography tandem mass spectrometry or calibrated chromogenic assays to reliably exclude plasma DOAC concentrations ≥30 ng/mL. CONCLUSION: Based on these data, a simple algorithm is proposed to enhance medical decision-making in acute care indications useful primarily in hospitals not having readily available quantitative tests and 24/7. This algorithm not only determines DOAC exposure but also differentiates between factor Xa and thrombin inhibitors to better guide clinical management.

Early Time Courses of Recurrent Venous Thromboembolism and Bleeding during Apixaban or Dalteparin Therapy for Patients with Cancer.

BACKGROUND: In patients with acute venous thromboembolism (VTE), the rates of recurrence and major bleeding are highest during the first weeks of anticoagulation. The CARAVAGGIO trial demonstrated noninferiority of apixaban to dalteparin for treatment of cancer-associated VTE without an increased risk of major bleeding. We compared the early time course of VTE recurrence and major bleeding events of apixaban compared with dalteparin at 7, 30, and 90 days of treatment in patients with cancer-associated VTE. METHODS: The study design of the CARAVAGGIO trial has been described. Eligible patients were randomly assigned to receive monotherapy with either apixaban or dalteparin for 6 months. The primary efficacy outcome was the incidence of objectively confirmed recurrent VTE. The primary safety outcome was major bleeding. RESULTS: In 1,155 patients, recurrent VTE after 7, 30, and 90 days occurred in 6 (1%), 15 (2.6%), and 27 (4.7%) patients in the apixaban arm versus 5 (0.9%), 20 (3.5%), and 36 (6.2%) patients respectively in the dalteparin arm. By day 7, 30, and 90, major bleeding events had occurred in 3 (0.5%), 9 (1.6%), and 16 (2.8%) patients in the apixaban group versus 5 (0.9%), 11 (1.9%), and 17 (2.9%) patients in the dalteparin group. CONCLUSION: The frequencies of recurrent VTE and major bleeding events at 7, 30, and 90 days of apixaban compared with dalteparin were similar in patients with cancer-associated VTE. This supports the use of apixaban for the initiation and early phase of anticoagulant therapy in cancer-associated VTE.

Acute pulmonary embolism and cancer: findings from the COPE study.

BACKGROUND: Patients with acute venous thromboembolism associated with cancer have an increased risk of recurrences and bleeding in the long term. RESEARCH QUESTION: To describe the clinical features and short-term course of patients with acute pulmonary embolism (PE) and active cancer, previous cancer or no cancer. STUDY DESIGN AND METHODS: Patients with acute PE included in COPE-prospective, multicentre study of adult patients with acute, symptomatic, objectively diagnosed PE-were classified as having active cancer, previous cancer, or no cancer. RESULTS: Overall, 832 patients had active cancer, 464 with previous cancer and 3660 patients had no cancer at the time of acute PE. The most prevalent primary sites of active cancer were urogenital (23.0%), gastrointestinal (21.0%), and lung (19.8%), with a high prevalence of metastatic disease (57.6%) and ongoing anticancer treatment (16.2%). At discharge, a direct oral anticoagulant was used in 43.1%, 78.8%, and 82.0% of patients with active cancer, previous cancer, and no cancer, respectively. Rates of death in-hospital and at 30 days were higher in patients with active cancer compared to patients with previous cancer and no cancer (7.9% vs. 4.3% vs. 2.2% and 13.8% vs. 5.2% vs. 2.6%, respectively). Rates of major bleeding were 4.8%, 2.6%, and 2.4%, respectively. Among patients with active cancer, lung or metastatic cancer were independent predictors of death; brain, hematological or gastrointestinal cancer had the highest risk of major bleeding. INTERPRETATION: Among patients with acute PE, those with active cancer have high risks for death or major bleeding within 30 days. These risks vary based on primary site of cancer. CLINICAL TRIAL REGISTRATION: clinicaltrial.gov identifier: NCT03631810.

Early predictors of clinical deterioration in intermediate-high risk pulmonary embolism: clinical needs, research imperatives, and pathways forward.

A subset of intermediate-high risk pulmonary embolism (PE) patients will suffer clinical deterioration in the early hours following the acute event. Current evidence-based guidelines for the management of acute PE have provided limited direction for identification of which intermediate-high risk PE patients will go on to develop haemodynamic decompensation. Furthermore, a paucity of data further hampers guideline recommendations regarding the optimal approach and duration of intensive monitoring, best methods to assess the early response to anticoagulation, and the ideal window for reperfusion therapy, if decompensation threatens. The aim of the present article is to identify the current unmet needs related to the early identification of intermediate-high risk PE patients at higher risk of clinical deterioration and mortality during the early hours after the acute cardiovascular event and suggest some potential strategies to further explore gaps in the literature.

Awake prone positioning for patients with COVID-19-related respiratory failure: a systematic review and meta-analysis.

The role of awake prone positioning (aPP) in patients with acute hypoxemic respiratory failure is debated. We performed a systematic review and meta-analysis to evaluate the role of aPP in acute respiratory failure related to COronaVIrus Disease-19 (COVID-19). Studies reporting on the clinical course of patients with acute respiratory failure related to COVID-19 treated or not treated by aPP were included in the systematic review and meta-analysis (ProsperoID: CRD42022333211). The primary study outcome was the composite of in-hospital death or orotracheal intubation; the individual components of the primary outcome were secondary study outcomes. The composite of in-hospital death or orotracheal intubation was available for 6 studies (1884 patients), five randomized and one prospective; a significant reduction in the risk of this outcome was observed in patients treated vs. not treated by aPP (33.5% vs. 39.8%; OR 0.73, 95% CI 0.60-0.89; I2 0%). In-hospital death was reported in 34 studies (6808 patients) and occurred in 17.4% vs. 23.5% of patients treated or not treated with aPP (random effect OR 0.60, 95% CI 0.46-0.79; I2 59%); orotracheal intubation was observed in 25.8% vs. 32.7% of patients treated or not treated with aPP (27 studies, 5369 patients; random effect OR 0.85, 95% CI 0.56-1.27; I2 84%). aPP reduces the risk for death or orotracheal intubation in patients with acute respiratory failure related to COVID-19. Further studies should be conducted to confirm the clinical benefit of aPP outside the ICU.Registration Prospero ID: CRD42022333211.

Provoked vs minimally provoked vs unprovoked VTE: does it matter?

Venous thromboembolism (VTE) is a multifactorial disease, and its risk depends on exposure to risk factors and predisposing conditions. Based on their strength of association with a VTE episode, risk factors are classified as major or minor and determined using a temporal pattern to be transient or persistent. All patients with VTE should receive anticoagulant treatment for at least 3 months in the absence of an absolute contraindication. Beyond this period, selected patients may be candidates for an extended phase of anticoagulation aimed at secondary VTE prevention. The risk of recurrent VTE if anticoagulation is discontinued is probably the main driver of decision-making regarding extended treatment. The risk of recurrence after VTE associated with major risk factors is low if the risk factor is no longer present. In this case, treatment can be discontinued. If the major risk factor is persistent, anticoagulation should be continued. After VTE occurring in the absence of risk factors, anticoagulation should probably be continued indefinitely if the risk for bleeding is low and preferably with minimal effective doses of anticoagulants. VTE occurring after exposure to minor risk factors is probably the most challenging situation, especially if the clinical manifestation was acute pulmonary embolism. Understanding the actual role of minor risk factors in the occurrence of VTE helps in estimating the risk of recurrence and avoiding the dangers associated with unnecessary anticoagulation. The availability of safer strategies for anticoagulation could allow personalized strategies for secondary prevention of VTE.

Contemporary anticoagulant treatment strategies in patients with acute pulmonary embolism at different risk for death.

INTRODUCTION: Availability of new treatment strategies for patients with acute pulmonary embolism (PE) have changed clinical practice with potential influence in short-term patients' outcomes. We aimed at assessing contemporary anticoagulation strategies and mortality in patients with acute PE included in the prospective, non-interventional, multicentre, COntemporary management of PE study. MATERIALS AND METHODS: Anticoagulant treatment at admission, during hospital-stay, at discharge and at 30-day are described in the overall population and by clinical severity. RESULTS: Overall, 5158 patients received anticoagulant treatment (99%); during the hospital-stay, 2298 received completely parenteral, 926 completely oral and 1934 parenteral followed by oral anticoagulation (1670 DOACs, 264 VKAs). Comorbidities and PE severity influenced the choice of in-hospital anticoagulation. The use of completely parenteral and completely oral anticoagulation varied based on PE severity. In patients treated with thrombolysis, DOACs were used in 46.4% and 80.1% during the hospital stay and at discharge, respectively. Death at 30 days occurred in 34.6% of patients not receiving anticoagulant treatment and in 1.5, 1.3, 3.4 and 8.1% of patients receiving completely oral, sequential with DOACs, sequential with VKAs and completely parenteral regimens, respectively. Increased mortality in patients receiving completely parenteral anticoagulation persisted after adjustment for PE severity. Completely oral anticoagulation was effective and safe also in patients at intermediate-high risk of death. CONCLUSIONS: Contemporary anticoagulation for acute PE includes parenteral agents in over 90% of patients; DOACs are used in the large majority of PE patients at discharge and their early use seems effective and safe also in selected intermediate-risk patients. TRIAL REGISTRATION NUMBER: NCT03631810.

Acute venous thromboembolism in patients with brain cancer: clinical course.

Background: Patients with brain cancer have been excluded or were underrepresented in studies on the treatment of venous thromboembolism (VTE), mainly due to the fear of intracranial hemorrhage (ICH). Objectives: The aim of this study was to provide data on the risk of ICH, recurrent VTE, and major bleeding in patients with active brain cancer. Methods: This was a multicenter, international cohort study at participating sites of the Registro Informatizado Enfermedad Tromboembólica Registry. Patients included in this study were classified as having known active brain cancer, active nonbrain cancer, or without active cancer. ICH at 3 months was the primary study outcome. Results: Overall, 98,377 patients with VTE were included: 616 with active brain cancer, 16,807 with active nonbrain cancer, and 80,954 without active cancer. At 3 months follow-up, ICH occurred in 2.8%, 0.3%, and 0.2% of the patients, respectively, and was fatal in 1.3%, 0.2%, and 0.1%, respectively. Both rates of major bleeding (3.7% vs 3.2% vs 1.5%, respectively) and recurrent VTE (3.9% vs 3.4% vs 1.1%, respectively) were higher in patients with brain or nonbrain cancer than in patients without cancer. Glioblastomas were associated with a numerically higher risk of ICH, fatal ICH, and recurrent VTE than other brain tumors. Conclusion: In patients with VTE, active brain cancer was associated with a higher risk of ICH or fatal ICH than nonbrain or no active cancer. Further studies are needed to assess the value of different treatment approaches in patients with brain cancer and VTE.

Arterial lactate as a risk factor for death in respiratory failure related to coronavirus disease 2019: an observational study.

BACKGROUND: Arterial lactate is a recognized biomarker associated with death in critically ill patients. The prognostic role of arterial lactate in acute respiratory failure due to the novel coronavirus disease 2019 (COVID-19) is unclear. OBJECTIVES: We aimed to investigate the prognostic role of arterial lactate levels at admission in patients with COVID-19-related acute respiratory failure. DESIGN AND METHODS: Cohorts of consecutive patients admitted to nonintensive care units (ICU) at study centers for COVID-19-related respiratory failure were merged into a collaborative database. The prognostic role of lactate levels at admission was assessed for continuous values and values ⩾2.0 mmol/l, and lactate clearance at 24 h through delta-lactate (ΔLac). The study outcome was 30-day in-hospital death. Cox proportional regression model was used to assess independent predictors of the study outcome. RESULTS: At admission, 14.6% of patients had lactate levels ⩾2 mmol/l. In-hospital death at 30 days occurred in 57 out of 206 patients; 22.3% and 56.7% with normal or ⩾ 2 mmol/l lactate at admission, respectively. The median lactate level was 1.0 [interquartile range (IQR) 0.8-1.3] mmol/l and 1.3 (IQR 1.0-2.1) mmol/l in survivors and nonsurvivors, respectively (p-value < 0.001). After adjusting for age, relevant comorbidities, acidemia, and the severity of respiratory failure, lactate ⩾2.0 mmol/l was associated with in-hospital death (HR 2.53, 95% CI 1.29-4.95, p-value 0.0066), while Δ Lac ⩾0 was not (HR 1.37, 95% CI 0.42-4.49). These results were confirmed in patients with a pO2/FiO2-ratio (P/F ratio) ⩽300 mmHg. CONCLUSIONS: In our study, increased arterial lactate at admission was independently associated with in-hospital death at 30 days in non-ICU patients with acute respiratory failure related to COVID-19.

A new strategy for anticoagulation: The factor XI inhibitors.

Direct oral anticoagulants (DOACs) are currently the first-choice therapy for the prevention of cardioembolic events in patients with atrial fibrillation and for the treatment of venous thromboembolism (VTE) due to their more favorable efficacy to safety profile in comparison to vitamin K antagonists (VKA). DOACs did not show a clinical benefit when used for in stroke prevention in patients with mechanic or rheumatic valves or in those who underwent transcatheter aortic valve implantation (TAVI), in the treatment of VTE in patients with antiphospholipid antibody syndrome and in prevention of VTE in medically ill patients. There are some concerns for bleeding excess at the gastrointestinal site for some, but not all, DOACs. In recent years, in order to overcome the limitations of the available DOACs and to explore the advantages of anticoagulation in additional clinical settings, the development of factor XI and factor XII inhibitors as anticoagulant agents has been proposed. Emerging data show that factor XI has a minor role in the physiological process of hemostasis and an important role in the development of thrombosis. Bleeding has been viewed for several years as an unavoidable side effect of anticoagulant therapy. The aim of factor XI inhibitors is to challenge this dogma by favoring the uncoupling between hemostasis and thrombosis. This paper provides an update on the rationale for the use of factor XI inhibitors, their pharmacological properties and the preliminary clinical findings.

Rivaroxaban Versus Low-Molecular-Weight Heparins in a Broad Cohort of Patients With Cancer-Associated Venous Thromboembolism: An Analysis of the OSCAR-US Program.

Cancer-associated venous thromboembolism (CAT) guidelines recommend direct oral anticoagulants as alternatives to low-molecular-weight heparin (LMWH) in most patients. This study compared the effectiveness and safety of rivaroxaban versus LMWH for a broad CAT cohort. The cohort study used electronic health data from January 2012 to December 2020 to evaluate patients with active cancer experiencing acute venous thromboembolism (VTE) and treated with rivaroxaban or LMWH. Propensity score-overlap weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE, bleeding-related hospitalization, and all-cause mortality were calculated. In total, 4935 patients were identified (27.9% on rivaroxaban and 72.1% on LMWH). The cancer types included gastrointestinal (29.4%), genitourinary (26.2%), lung (24.0%), breast (19.7%), and hematologic (14.4%). Rivaroxaban was associated with a reduction in recurrent VTE versus LMWH among all patients with cancer (HR = 0.78; 95%CI = 0.61-0.99) at 3 months. No differences in bleeding-related hospitalization or all-cause mortality were observed. Directionally similar results to those at 3 months were observed at 6 months for all outcomes. In conclusion, we observed fewer recurrent VTE cases and no increase in bleeding-related hospitalizations with rivaroxaban versus LMWH at 3 months in this patient cohort with various cancer types.

Rivaroxaban versus Apixaban for Treatment of Cancer-Associated Venous Thromboembolism in Patients at Lower Risk of Bleeding.

This retrospective study, utilizing U.S. electronic health record (EHR) data from January 2013 to December 2020, sought to assess whether rivaroxaban and apixaban had similar effectiveness and safety in the treatment of cancer-associated venous thromboembolism (VTE) in patients with a cancer type not associated with a high risk of bleeding. We included adults diagnosed with active cancer, excluding esophageal, gastric, unresected colorectal, bladder, noncerebral central nervous system cancers and leukemia, who experienced VTE and received a therapeutic VTE dose of rivaroxaban or apixaban on day 7 post-VTE, and were active in the EHR ≥12 months prior to the VTE. Primary outcome was the composite of recurrent VTE or any bleed resulting in hospitalization at 3 months. Secondary outcomes included recurrent VTE, any bleed resulting in hospitalization, any critical organ bleed, and composites of these outcomes at 3 and 6 months. Inverse probability of treatment-weighted Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 1,344 apixaban and 1,093 rivaroxaban patients. At 3 months, rivaroxaban was found to have similar hazard to apixaban for developing recurrent VTE or any bleed resulting in hospitalization (HR: 0.87; 95% CI: 0.60-1.27). No differences were observed between cohorts for this outcome at 6 months (HR: 1.00; 95% CI: 0.71-1.40) or for any other outcome at 3 or 6 months. In conclusion, patients receiving rivaroxaban or apixaban showed similar risks of the composite of recurrent VTE or any bleed resulting in hospitalization in patients with cancer-associated VTE. This study was registered at www.clinicaltrials.gov as #NCT05461807. Key Points Rivaroxaban and apixaban have similar effectiveness and safety for treatment of cancer-associated VTE through 6 months.Clinicians should therefore consider patient preference and adherence when choosing the optimal anticoagulant.

Anticoagulation in acute ischemic stroke patients with mechanical heart valves: To bridge or not with heparin. The ESTREM study.

INTRODUCTION: The best therapeutic strategy for patients with mechanical heart valves (MHVs) having acute ischemic stroke during treatment with vitamin K antagonists (VKAs) remain unclear. Being so, we compared the outcomes for: (i) full dose heparin along with VKA (bridging therapy group) and (ii) restarting VKA without heparin (nonbridging group). PATIENTS AND METHODS: For this multicenter observational cohort study, data on consecutive acute ischemic stroke patients with MHV was retrospectively collected from prospective registries. Propensity score matching (PSM) was adopted to adjust for any treatment allocation confounders. The primary outcome was the composite of stroke, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding at 90 days. RESULTS: Overall, 255 out of 603 patients (41.3%) received bridging therapy: 36 (14.1%) had combined outcome, compared with 28 (8.0%) in the nonbridging group (adjusted OR 1.83; 95% CI 1.05-3.18; p = 0.03). Within the bridging group, 13 patients (5.1%) compared to 12 (3.4%) in the nonbridging group had an ischemic outcome (adjusted OR 1.71; 95% CI 0.84-3.47; p = 0.2); major bleedings were recorded in 23 (9.0%) in the bridging group and 16 (4.6%) in the nonbridging group (adjusted OR 1.88; 95% CI 0.95-3.73; p = 0.07). After PSM, 36 (14.2%) of the 254 bridging patients had combined outcome, compared with 23 (9.1%) of 254 patients in the nonbridging group (OR 1.66; 95% CI 0.95-2.85; p = 0.07). CONCLUSION: Acute ischemic stroke patients with MHV undergoing bridging therapy had a marginally higher risk of ischemic or hemorrhagic events, compared to nonbridging patients.