[Interference of oral anti-Xa anticoagulants during monitoring of unfractionated heparin treatments: practical and future attitudes]. / Interférence des anticoagulants oraux directs anti-Xa lors de la surveillance des traitements par héparine non-fractionnée : attitudes pratiques et à venir.

Contrary to direct oral anticoagulants (DOAC), unfractionated heparin (UFH) requires daily monitoring when administered at therapeutic dose. At present, UFH monitoring is preferably carried out by measuring plasma anti-Xa activity, however, in patients previously treated with an anti-Xa DOAC and switched to UFH, there is a high risk of DOAC interfering with the measurement of UFH anti-Xa activity. Residual anti-Xa DOAC in the sample can lead to an overestimation of the anticoagulant activity attributed to heparin and thus to incorrect anticoagulation. This risk of interference should not be overlooked because interference may occur even at concentration of DOAC below the hemostatic safety threshold and can last several days. To overcome this issue, several alternatives are being studied. This note provides an update on anti-Xa DOAC interference and different strategies available in current practice. It also underlines the importance of communication between biologists and clinicians on anticoagulant treatments received by patients.

Quality control, safety assessment and preparation approaches of low molecular weight heparin.

Low Molecular Weight Heparins (LMWHs) are well-established for use in the prevention and treatment of thrombotic diseases, and as a substitute for unfractionated heparin (UFH) due to their predictable pharmacokinetics and subcutaneous bioavailability. LMWHs are produced by various depolymerization methods from UFH, resulting in heterogeneous compounds with similar biochemical and pharmacological properties. However, the delicate supply chain of UFH and potential contamination from animal sources require new manufacturing approaches for LMWHs. Various LMWH preparation methods are emerging, such as chemical synthesis, enzymatic or chemical depolymerization and chemoenzymatic synthesis. To establish the sameness of active ingredients in both innovator and generic LMWH products, the Food and Drug Administration has implemented a stringent scientific method of equivalence based on physicochemical properties, heparin source material and depolymerization techniques, disaccharide composition and oligosaccharide mapping, biological and biochemical properties, and in vivo pharmacodynamic profiles. In this review, we discuss currently available LMWHs, potential manufacturing methods, and recent progress for manufacturing quality control of these LMWHs.

Overview of the current procedures in synthesis of heparin saccharides.

Natural heparin, a glycosaminoglycan consisting of repeating hexuronic acid and glucosamine linked by 1 â†’ 4 glycosidic bonds, is the most widely used anticoagulant. To subvert the dependence on animal sourced heparin, alternative methods to produce heparin saccharides, i.e., either heterogenous sugar chains similar to natural heparin, or structurally defined oligosaccharides, are becoming hot subjects. Although the success by chemical synthesis of the pentasaccharide, fondaparinux, encourages to proceed through a chemical approach generating homogenous product, synthesizing larger oligos is still cumbersome and beyond reach so far. Alternatively, the chemoenzymatic pathway exhibited exquisite stereoselectivity of glycosylation and regioselectivity of modification, with the advantage to skip the tedious protection steps unavoidable in chemical synthesis. However, to a scale of drug production needed today is still not in sight. In comparison, a procedure of de novo biosynthesis in an organism could be an ultimate goal. The main purpose of this review is to summarize the current available/developing strategies and techniques, which is expected to provide a comprehensive picture for production of heparin saccharides to replenish or eventually to replace the animal derived products. In chemical and chemoenzymatic approaches, the methodologies are discussed according to the synthesis procedures: building block preparation, chain elongation, and backbone modification.

A Comparison Between Fondaparinux Sodium and Low-Molecular-Weight Heparin in Preventing Patients Undergoing Hip Replacement from Deep Vein Thrombosis.

OBJECTIVES: Total hip arthroplasty (THA) is a highly successful and effective surgery for improving hip functions and relieving pain. However, the lower extremities are prone to deep vein thrombosis (DVT) and swelling after surgery, thereby delaying recovery. In this study, we investigated the preventive effects of fondaparinux sodium (FS) and low-molecular-weight heparin (LMWH) on DVT of the lower extremity after THA. METHODS: Firstly, 60 patients who underwent THA at the First Affiliated Hospital of Wannan Medical College from March 2020 to December 2020 were included. Next, the patients were randomly divided into an LMWH group (n = 30) and an FS group (n = 30). Then, the indexes related to DVT were compared between both groups. RESULTS: Specifically, the differences in baseline data, such as age, gender and body mass index (BMI), between the two groups were not statistically significant. The postoperative weight bearing time of patients in the FS group was much shorter than that in the LMWH group. CONCLUSION: Subcutaneous injection of FS not only exhibits superior effects to LMWH in preventing DVT after THA but also has a correlation with reducing the risk of thrombosis and improving patient symptoms.

[Heparin-Induced Thrombocytopenia].

The extensive use of therapeutic doses of heparin to prevent thrombosis in critically ill patients with COVID-19 during the pandemic has led to an increased incidence of bleeding and heparin-induced thrombocytopenia (HIT). In addition, the introduction of the AstraZeneca and Johnson&Johnson vaccines against COVID-19 into clinical practice was associated with the development of a rare but very severe, adverse thrombotic complication, vaccine-induced immune thrombotic thrombocytopenia (VITT). Thrombotic complications of VITT turned out to be similar to HIT both clinically and pathophysiologically. HIT is a potentially fatal immune-mediated adverse drug response that results in emergence of antibodies that activate platelets in the presence of heparin. HIT is characterized by a high incidence of venous and arterial thromboses, often with fatal outcomes. Currently, there are clearly defined international guidelines for the diagnosis, treatment and prevention of HIT. In case of thrombotic complications, non-heparin anticoagulants should be used.

Thromboembolic and bleeding complications after elective cardioversion of atrial fibrillation: a nationwide cohort study.

AIMS: Elective cardioversion (ECV) is routinely used in atrial fibrillation (AF) to restore sinus rhythm. However, it includes a risk of thromboembolism even during adequate oral anticoagulation treatment. The aim of this study was to evaluate the risk of thromboembolic and bleeding complications after ECV in a real-life setting utilizing data from a large AF population. METHODS AND RESULTS: This nationwide register-based study included all (n = 9625) Finnish AF patients undergoing their first-ever ECV between 2012 and 2018. The thromboembolic and bleeding complications within 30 days after ECV were analysed. The mean age of the patients was 67.7 ± 9.9 years, 61.2% were men, and the mean CHA2DS2-VASc score was 2.6 ± 1.6. Warfarin was used in 6245 (64.9%) and non-vitamin K oral anticoagulants (NOACs) in 3380 (35.1%) cardioversions. Fifty-two (0.5%) thromboembolic complications occurred, of which 62% were ischaemic strokes, 25% transient ischaemic attacks, and 13% other systemic embolisms. Thromboembolic events occurred in 14 (0.4%) NOAC-treated patients and in 38 (0.6%) warfarin-treated patients (odds ratio 0.77; confidence interval: 0.42-1.39). The median time from ECV to the thromboembolic event was 2 days, and 78% of the events occurred within 10 days. Age and alcohol abuse were significant predictors of thromboembolic events. Among warfarin users, thromboembolic complications were more common with international normalized ratio (INR) <2.5 than INR ≥2.5 (0.9% vs. 0.4%, P = 0.026). Overall, 27 (0.3%) bleeding events occurred. CONCLUSION: The rate of thromboembolic and bleeding complications related to ECV was low without significant difference between NOAC- and warfarin-treated patients. With warfarin, INR ≥2.5 at the time of cardioversion reduced the risk of thromboembolic complications.

[How to generate recommendations for venous thromboprophylaxis in health institutions?] / Cómo generar recomendaciones de tromboprofilaxis venosa en instituciones de salud.

Venous thromboembolism disease (VTE) prevention strategy has to be constantly updated based on new evidence that is generated every year. Each institution must have a formal and active prevention policy against VTE and must develop guidelines or standards for thromboprophylaxis (TP) according to the local reality. During this process of adapting a guideline to the region and the generation of hospital recommendations, we must always consider the available local resources, the thromboembolic and hemorrhagic risk of the patients, even after discharge, and also their considerations and preferences. Adherence to local TP recommendations is one of the most important items evaluated by organizations that measure institutional quality. Individualized prophylaxis should consider personal and family history of VTE, the use of validated risk assessment models or RAMs for thrombosis and bleeding events, as well as the special characteristics of each patient. Ideally, each center's own statistics should be available for decision-making. Extrapolating guidelines from developed countries could have a negative impact, if we ignore our hospital's reality. In this document we will find practical tools for health institutions that will allow them to prepare recommendations or guidelines for adequate VTE prophylaxis.

La prevención de la enfermedad tromboembólica venosa (ETV) es motivo de continua actualización en función de nueva evidencia que se genera permanentemente. Cada institución debe contar con una estrategia activa de prevención contra la ETV y debe generar normas de tromboprofilaxis (TP) de acuerdo con la realidad local. Durante este proceso de adaptación de una guía a la región debemos siempre tener en cuenta los recursos locales disponibles, el riesgo tromboembólico y hemorrágico propio del paciente, de la enfermedad por la que se encuentra internado (ya sea clínica o quirúrgica) y las consideraciones o preferencias del paciente. La tasa de adherencia a recomendaciones locales de TP es uno de los indicadores de excelencia más importantes evaluados en organismos que califican la calidad de una institución de salud. Las medidas de profilaxis que propongamos para los centros de salud, deben ser individualizadas para cada paciente, tienen que considerar antecedentes personales y familiares del enfermo y utilizar modelos de evaluación de riesgo validados de trombosis y de sangrado. También deben incluir a la población con riesgo de trombosis persistente luego del alta. Lo ideal es tener estadísticas propias de cada nosocomio para la toma de decisiones de cómo implementar una correcta TP. Extrapolar guías de los países desarrollados a nuestro ámbito podría tener un impacto negativo, si no se conoce la propia realidad. En este documento encontraremos herramientas prácticas para las instituciones de salud de la región, que les permita orientarse al momento de confeccionar recomendaciones para una adecuada TP.

Anticoagulant rodenticide toxicity in dogs: A retrospective study of 349 confirmed cases in Saskatchewan.

Objective: To evaluate the signalment and clinical, laboratory, treatment, and outcome features of dogs diagnosed with anticoagulant rodenticide (AR) intoxication in Saskatchewan. Animals: We studied 349 dogs. Procedure: Medical records from the Veterinary Medical Centre (Saskatoon, Saskatchewan) between 1999 and 2022 were reviewed. Cases were included if they met at least 1 of the following criteria: owner witnessed the dog ingesting an AR; AR was seen in the vomitus when emesis was induced; the dog had clinical signs of coagulopathy, with elevation of PT ± aPTT that normalized after vitamin K1 therapy, in the presence of appropriate clinical and paraclinical data and the absence of other causes of hypocoagulable state determined by the primary clinician. Results: Fifty-three percent of cases were seen between July and October. Most dogs (61%) came from an urban setting. Ninety-two percent of dogs ingested a 2nd-generation AR and the most frequent toxin was bromadiolone. Clinical signs were reported in 30% of AR intoxications and included lethargy (86%), dyspnea (55%), and evidence of external hemorrhage (44%). The most common site of hemorrhage was the pleural space, accounting for 43% of hemorrhage sites. Consumptive thrombocytopenia was reported in 24% of dogs with evidence of AR-induced hemorrhage, with moderate (platelet count < 60 K/µL) and marked (< 30 K/µL) thrombocytopenia in 7/12 and 2/12 dogs, respectively. Blood products were administered to 84% of dogs with AR-induced hemorrhage; the most common product administered was fresh frozen plasma (56% of cases). Among dogs with AR-induced hemorrhage, those that received blood products were more likely to survive to discharge (81%) compared to those that did not (19%) (P = 0.017). Eighty-six percent of dogs with AR-induced hemorrhage survived to discharge. Conclusion and clinical relevance: The pleural space was the most common site of hemorrhage. Moderate thrombocytopenia was a common finding. Eighty-six percent of dogs with AR-induced hemorrhage survived to discharge.

Toxicité des rodenticides anticoagulants chez les chiens : étude rétrospective de 349 cas confirmés en Saskatchewan. Objectif: Évaluer le signalement et les caractéristiques cliniques, de laboratoire, de traitement et de résultats des chiens diagnostiqués avec une intoxication par un rodenticide anticoagulant (AR) en Saskatchewan. Animaux: Nous avons étudié 349 chiens. Procédure: Les dossiers médicaux du Veterinary Medical Centre (Saskatoon, Saskatchewan) entre 1999 et 2022 ont été examinés. Les cas ont été inclus s'ils répondaient à au moins 1 des critères suivants : le propriétaire a vu le chien ingérer un AR; de l'AR a été observée dans les vomissures lorsque des vomissements ont été provoqués; le chien présentait des signes cliniques de coagulopathie, avec une élévation du PT ± aPTT qui s'est normalisée après un traitement par la vitamine K1, en présence de données cliniques et paracliniques appropriées et en l'absence d'autres causes d'état hypocoagulable déterminées par le clinicien initial. Résultats: Cinquante-trois pour cent des cas ont été observés entre juillet et octobre. La plupart des chiens (61 %) venaient d'un milieu urbain. Quatre-vingt-douze pour cent des chiens ont ingéré un AR de 2e génération et la toxine la plus fréquente était la bromadiolone. Des signes cliniques ont été rapportés dans 30 % des intoxications par AR et incluaient de la léthargie (86 %), de la dyspnée (55 %) et des signes d'hémorragie externe (44 %). Le site d'hémorragie le plus fréquent était l'espace pleural, représentant 43 % des sites d'hémorragie. Une thrombocytopénie de consommation a été rapportée chez 24 % des chiens présentant des signes d'hémorragie induite par l'AR, avec une thrombocytopénie modérée (nombre de plaquettes < 60 K/µL) et marquée (< 30 K/µL) chez 7 chiens sur 12 et 2 chiens sur 12, respectivement. Des produits sanguins ont été administrés à 84 % des chiens présentant une hémorragie induite par l'AR; le produit le plus fréquemment administré était le plasma frais congelé (56 % des cas). Parmi les chiens présentant une hémorragie induite par l'AR, ceux qui ont reçu des produits sanguins étaient plus susceptibles de survivre jusqu'à leur congé (81 %) que ceux qui n'en ont pas reçu (19 %) (P = 0,017). Quatre-vingt-six pour cent des chiens présentant une hémorragie induite par l'AR ont survécu jusqu'à leur sortie. Conclusion et pertinence clinique: L'espace pleural était le site d'hémorragie le plus fréquent. Une thrombocytopénie modérée était fréquente. Quatre-vingt-six pour cent des chiens présentant une hémorragie induite par l'AR ont survécu jusqu'à leur sortie.(Traduit par Dr Serge Messier).

Epidemiological, clinical, therapeutic and evolutionary specificities of the association between venous thromboembolic event and cancer in sub-Saharan Africa: Case of Togo.

BACKGROUND: Our study aimed to describe the clinical, paraclinical, therapeutic and outcomes of patients with venous thromboembolic event (VTE) associated with cancer in the context of limited resources. MATERIALS AND METHODS: This was a descriptive cross-sectional study over a period of six years from March 1, 2016 to March 31, 2022, in the cardiology department and the oncology unit of the Sylvanus Olympio Teaching Hospital of Lome. Our study examined medical records of patients who were at least 18 years old and had venous thromboembolic disease and cancer that was histologically confirmed. This study did not include records that were incomplete or records from patients with coronavirus disease. RESULTS: Our study included 87 patients with average age of 56.36±15.26 years. The discovery of VTE occurred incidentally in 28.74%. Venous thrombosis was isolated in 68.96% and proximal in 95%. Pulmonary embolism was bilateral in 77.77%. Gynaecological and urological cancers were found in 33.33% and 32.19% respectively. Adenocarcinoma was the histological type of cancer found in 47.13%. Cancers were at a very advanced stage in 74.71%. Treatment with antivitamin K was prescribed in 12.65%. In our study, there were 58 patients who passed away with a mortality rate of 66.66%. The cause of death was a complication of VTE in 22.42% and related to the course of cancer in 63.79% of cases. CONCLUSION: VTE during cancer is particular with a fatal evolution due to the severity of VTE and the very advanced stage of cancer.

Recurrent intra-cardiac thrombosis: A rare manifestation of Behçet's disease.

Behçet's disease is a systemic vasculitis characterized by recurrent bipolar aphtosis and ophthalmic disorders. Cardiac involvement is rarely reported and could be associated to poor prognosis. Intracardiac thrombosis is exceptional and represents a therapeutic issue. We report the case of a young man admitted in internal medicine department for management of prolonged fever and recurrent mouth ulcers.

Cost-effectiveness of enoxaparin versus aspirin in the prevention of venous thromboembolism after total hip or knee arthroplasty: an analysis from the CRISTAL cluster-randomized trial.

Aims: The aim of this study was to evaluate the healthcare costs and benefits of enoxaparin compared to aspirin in the prevention of symptomatic venous thromboembolism (VTE) after total hip arthroplasty (THA) or total knee arthroplasty (TKA) using data from the CRISTAL trial. Methods: This trial-based economic analysis reports value for money as incremental cost per quality-adjusted life-year (QALY) gained in 2022 Australian dollars, compared to a single threshold value of AUD$70,000 per QALY. Event costs were estimated based on occurrence of VTEs and bleeds, and on published guidelines for treatment. Unit costs were taken from Australian sources. QALYs were estimated using CRISTAL six-month follow-up data. Sensitivity analyses are presented that vary the cost of VTE treatment, and extend the analyses to two years. Results: The CRISTAL trial found that enoxaparin was more effective than aspirin in preventing symptomatic VTE within 90 days of THA or TKA (risk difference 1.97% (95% confidence interval (CI) 0.54% to 3.41%; p = 0.007)). The additional cost after a THA or TKA was AUD$83 (95% CI 68 to 97) for enoxaparin, and enoxaparin resulted in an additional 0.002 QALYs (95% CI -0.002 to 0.005). Incremental cost per QALY gained was AUD$50,567 (95% CI 15,513, dominated) for enoxaparin. We can be 60% confident that the incremental cost per QALY does not exceed the willingness-to-pay threshold of AUD$70,000. Increasing the cost of VTE treatment and extension of costs and consequences to two years suggested greater confidence that enoxaparin is good value for money (70% and 63% confidence, respectively). Conclusion: This analysis provides strong evidence that enoxaparin thromboprophylaxis following THA or TKA reduced VTEs, but weak evidence of net economic benefits over aspirin. If the value of avoiding VTEs is high, and there is a strong likelihood of VTE-related health impairments, we can be more confident that enoxaparin is cost-effective compared to aspirin.

[Translation into French and republication of: "Management of venous thromboembolic disease in patients with malignant brain tumours"]. / Traduction et republication de : « Prise en charge de la maladie thromboembolique veineuse chez les patients atteints de tumeurs cérébrales malignes ¼.

This article addresses the management of venous thromboembolism in patients with malignant brain tumours, including both primary and secondary (metastatic) tumours. The available data on patients on venous thromboembolism recurrence and bleeding risks in patients with brain tumours is limited, since these patients have been excluded from most randomised, interventional, head-to-head, clinical trials comparing low molecular weight heparins to vitamin K antagonists or to direct oral factor Xa inhibitors. More information is available from retrospective observational studies, which however were generally small, and carried a high risk of confounding. Their findings suggest that direct factor Xa inhibitor use is associated with lower rates of intracranial haemorrhage compared with low molecular weight heparins. Overall, the safety profile of direct oral factor Xa inhibitors when used to prevent venous thromboembolism recurrence in patients with either primary or secondary brain tumours appears to be favourable. The available data are in favour of using an anticoagulant at a full therapeutic dose in patients with primary and secondary brain tumours experiencing a venous thromboembolism, although they are not yet sufficiently robust to permit recommending a direct factor Xa inhibitor over low-molecular weight heparin.

[Translation into French and republication of: "Recurrent venous thromboembolism in anticoagulated cancer patients: diagnosis and treatment"]. / Traduction et republication de : « Maladie thromboembolique veineuse récidivante chez les patients cancéreux anticoagulés : diagnostic et traitement ¼.

Patients with cancer are at significantly increased risk of venous thromboembolism (VTE), due both to the impact of malignant disease itself and to the impact of certain anticancer drugs on haemostasis. This is true both for first episode venous thromboembolism and recurrence. The diagnosis and management of VTE recurrence in patients with cancer poses particular challenges, and these are reviewed in the present article, based on a systematic review of the relevant scientific literature published over the last decade. Furthermore, it is uncertain whether diagnostic algorithms for venous thromboembolism, validated principally in untreated non-cancer patients, are also valid in anticoagulated cancer patients: the available data suggests that clinical decision rules and D-dimer testing perform less well in this clinical setting. In patients with cancer, computed tomography pulmonary angiography and venous ultrasound appear to be the most reliable diagnostic tools for diagnosis of pulmonary embolism and deep vein thrombosis respectively. Options for treatment of venous thromboembolism include low molecular weight heparins (at a therapeutic dose or an increased dose), fondaparinux or oral direct factor Xa inhibitors. The choice of treatment should take into account the nature (pulmonary embolism or VTE) and severity of the recurrent event, the associated bleeding risk, the current anticoagulant treatment (type, dose, adherence and possible drug-drug interactions) and cancer progression.

Early vs late anticoagulation in acute ischemic stroke with indications outside atrial fibrillation.

BACKGROUND: Current literature lacks guidance on the safety of administering anticoagulation in acute ischemic stroke with emergent indications that require anticoagulation other than atrial fibrillation. Therefore, we tend to rely on studies investigating acute ischemic stroke in atrial fibrillation for anticoagulation recommendations. METHODS: We retrospectively reviewed data for patients with acute ischemic stroke who had a non-atrial fibrillation emergent indication for anticoagulation (e.g., intra-arterial thrombus, intracardiac thrombus, acute coronary syndrome, acute limb ischemia, deep vein thrombosis and pulmonary embolism) diagnosed within 3 days of acute ischemic stroke. Patients who received anticoagulation ≤ 3 days of stroke onset (Group A) were compared to those who either received it afterwards or did not receive it at all (Group B). RESULTS: Out of the 558 patients, only 88 patients met our inclusion criteria. Of the total cohort, 55.7 % patients were males, and basic demographics were similar in both groups except for milder strokes in Group A (national institute of health stroke scale 6 vs. 12.5, p = 0.03). Only 2 patients in Group A and 1 patient in Group B developed intracranial hemorrhage, which was not statistically significant. Group A patients had a lower incidence of both new diagnosis (2 % vs. 34.2 % %, p < 0.001) and propagation of an established venous thromboembolism. They also had a lower rate of any thromboembolic complication (2 % vs. 42 %, p < 0.001). CONCLUSION: Early anticoagulation (i.e., ≤ 3 days) in non-atrial fibrillation ischemic stroke patients with an emergent indication may be safe and carry a lower risk of thromboembolic complications than later anticoagulation.

Anticoagulants versus Antiplatelet Treatment in the Medical Management of Carotid Floating Thrombus.

BACKGROUND: Carotid free-floating thrombus (CFT) is a rare cause of stroke describing an intraluminal thrombus that is loosely associated with the arterial wall and manifesting as a filling defect fully surrounded by flow on vascular imaging. Unfortunately, there is no clear consensus among experts on the ideal treatment for this pathology. METHODS: Retrospective analysis of acute ischemic stroke (AIS) and transient ischemic attack (TIA) patients diagnosed with CFT on computed tomography angiogram (CTA) between January 2015-March 2023. We aimed to compare two treatment regimens: anticoagulation (ACT) and antiplatelet (APT) in the treatment of CFT. APT regimens included the use of dual or single antiplatelets (DAPT or SAPT; aspirin, clopidogrel and ticagrelor) and ACT regimens included the use of direct oral anticoagulants, warfarin, heparin or low molecular weight heparin +/- ASA. Patients that underwent mechanical thrombectomy were excluded. RESULTS: During study time there were 8252 acute ischemic stroke hospitalizations, of which 135 (1.63 %) patients were diagnosed with CFT. Sixty-six patients were included in our analysis. Patients assigned to APT were older (60.41years ± 12.82;p < 0.01). Other demographic variables were similar between ACT and APT groups. Complete CFT resolution on repeat vascular imaging was numerically higher at 30 days (58.8 vs 31.6 %, respectively; p = 0.1) and at latest follow-up (70.8 vs 50 %; p = 0.1) on ACT vs APT, respectively without reaching statistical significance. Similarly, there was numerically higher rates of any ICH with ACT compared to APT but it did not achieve statistical significance (27.6 % vs 13.5 %; p = 0.5). There were similar rates of PH1/2 hemorrhagic transformation, independence at discharge and similar hospital length of stay between ACT and APT groups. Patients assigned to APT were more likely to be discharged on their assigned treatment compared to those assigned to ACT (86.5 vs 55.2 %; p < 0.001). The rate of 30-day recurrent stroke was comparable among ACT and APT at 30 days (3.4 vs 0 %; p = 0.1, respectively). Subgroup analysis comparing exclusive ACT vs Dual APT lead to similar results. CONCLUSION: Our study showed comparable efficacy and safety outcomes in CFT patients who were exclusively managed medically with ACT vs APT. Larger prospective studies are needed.

Assessment of Days Alive Out of Hospital as a Possible End Point in Trials of Stroke Prevention for Atrial Fibrillation: A ROCKET AF Analysis.

BACKGROUND: Days alive out of hospital (DAOH) is an objective and patient-centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations. METHODS AND RESULTS: ROCKET AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) was an international double-blind, double-dummy randomized clinical trial that compared rivaroxaban with warfarin in patients with atrial fibrillation at increased risk for stroke. We assessed DAOH using investigator-reported event data for up to 12 months after randomization in ROCKET AF. We assessed DAOH overall, by treatment group, and by subgroup, including age, sex, and comorbidities, using Poisson regression. The mean±SD number of days dead was 7.3±41.2, days hospitalized was 1.2±7.2, and mean DAOH was 350.7±56.2, with notable left skew. Patients with comorbidities had fewer DAOH overall. There were no differences in DAOH by treatment arm, with mean DAOH of 350.6±56.5 for those randomized to rivaroxaban and 350.7±55.8 for those randomized to warfarin (P=0.86). A sensitivity analysis found no difference in DAOH not disabled with rivaroxaban versus warfarin (DAOH not disabled, 349.2±59.5 days and 349.1 days±59.3 days, respectively, P=0.88). CONCLUSIONS: DAOH did not identify a treatment difference between patients randomized to rivaroxaban versus warfarin. This may be driven in part by the low overall event rates in atrial fibrillation anticoagulation trials, which leads to substantial left skew in measures of DAOH.