Rivaroxaban vs Vitamin K Antagonist in Patients With Atrial Fibrillation and Advanced Chronic Kidney Disease.

Background: Treatment with vitamin K antagonists (VKAs) has been linked to worsening of kidney function in patients with atrial fibrillation (AF). Objectives: XARENO (Factor XA-inhibition in RENal patients with non-valvular atrial fibrillation Observational registry; NCT02663076) is a prospective observational study comparing adverse kidney outcomes in patients with AF and advanced chronic kidney disease receiving rivaroxaban or VKA. Methods: Patients with AF and an estimated glomerular filtration rate (eGFR) of 15 to 49 mL/min/1.73 m2 were included. Blinded adjudicated outcome analysis evaluated adverse kidney outcomes (a composite of eGFR decline to <15 mL/min/1.73 m2, need for chronic kidney replacement therapy, or development of acute kidney injury). A composite net clinical benefit outcome (stroke or systemic embolism, major bleeding, myocardial infarction, acute coronary syndrome, or cardiovascular death) was also analyzed. HRs with 95% CIs were calculated using propensity score overlap weighting Cox regression. Results: There were 1,455 patients (764 rivaroxaban; 691 VKA; mean age 78 years; 44% females). The mean eGFR was 37.1 ± 9.0 in those receiving rivaroxaban and 36.4 ± 10.1 mL/min/1.73 m2 in those receiving VKA. After a median follow-up of 2.1 years, rivaroxaban was associated with less adverse kidney outcomes (HR: 0.62; 95% CI: 0.43-0.88) and all-cause death (HR: 0.76, 95% CI: 0.59-0.98). No significant differences were observed in net clinical benefit. Conclusions: In patients with AF and advanced chronic kidney disease, those receiving rivaroxaban had less adverse kidney events and lower all-cause mortality compared to those receiving VKA, supporting the use of rivaroxaban in this high-risk group of patients.

Risk Profiles and Treatment Patterns in Atrial Fibrillation Patients with Chronic Kidney Disease Receiving or not Receiving Anticoagulation Therapy.

Background Patients with atrial fibrillation (AF) and chronic kidney disease (CKD) are at high risk for both thromboembolism and bleeding events. The latter induces a potential reason for withholding oral anticoagulation (OAC) despite an indication for prophylaxis of thromboembolic events. Methods AF patients with CKD (estimated glomerular filtration [eGFR] rate between 15 and 49 mL/min per 1.73 m 2 ) were included in a prospective international registry in Europe between 2016 and 2020, that is, XARENO (factor XA inhibition in renal patients with nonvalvular atrial fibrillation observational registry). The study enrolled adult patients treated at the discretion of physicians with rivaroxaban, vitamin K antagonists (VKA), or without OAC (w/oOAC). Here, we report a prespecified explorative baseline comparison between patients receiving OAC or no OAC within XARENO. Results In total, 1,544 patients (mean age: 78.2 years, mean eGFR: 36.2 mL/min) were studied (rivaroxaban n = 764, VKA n = 691, w/oOAC n = 89). Patients in the w/oOAC group were older and had a similar stroke (mean CHA 2 DS 2 -VASc score 4.0) but higher bleeding risk (mean modified Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly score 2.5 vs. 1.8) compared with the OAC groups. The distribution of comorbidities including hypertension, diabetes, and heart failure was similar. Treatment with antiplatelet drugs was fivefold more frequent in the w/oOAC group. Conclusion Only 5.8% of the overall population of AF patients with advanced CKD received no OAC. These patients were older and had a higher bleeding risk, which might explain this decision, but which contrasts with the more frequent use of antiplatelet drugs in this vulnerable group of patients.

Quality of life in elderly patients with venous thromboembolism assessed using patient-reported outcome measures.

BACKGROUND: We aimed to evaluate the quality of life (QoL), using patient-reported outcome measures (PROMs), in elderly patients with venous thromboembolism (VTE) and to explore whether VTE complications (recurrence, bleeding, or postthrombotic syndrome) had an impact on later QoL. METHODS: We used data from the SWIss venous Thromboembolism COhort of older patients(SWITCO65+), a prospective multicenter cohort of patients aged ≥65 years with acute, symptomatic VTE. Primary outcome was changes in QoL up to 24 months, assessed using generic (36-Item Short-Form Health Survey), with physical (PCS) and mental component score (MCS), and disease-specific (Venous Insufficiency Epidemiological and Economic Study [VEINES]-QoL, [VEINES-Sym], and Pulmonary Embolism QoL) PROMs. PROM scores ranged from 0 to 100 points, higher scores indicating a better QoL. Longitudinal latent class analysis was used to group patients with similar PCS trajectories. Repeated-measures linear regression analyses were used to assess effects of VTE complications on changes in QoL scores. RESULTS: In 923 patients (median age, 75; male, 54%), 140 (15%) patients died, 97 (11%) experienced recurrent VTE, and 106 (12%) major bleeding during follow-up. Compared with patients with higher PCS trajectories, patients with lower PCS trajectories were more likely to be older, female, sicker, and less physically active. On average, generic and disease-specific QoL scores improved over time (+11% in PCS, +3% in MCS, +6% in VEINES QoL, and +16% in Pulmonary Embolism QoL at 3 months). VTE complications were always associated with significantly lower QoL scores (for VTE recurrence: PCS adjusted difference -2.57, 95% CI, -4.47 to -0.67). CONCLUSION: Although QoL following VTE tended to improve over time, patients with VTE-related complications had lower QoL than patients without complications.

Inter-hospital comparison of working time allocation among internal medicine residents using time-motion observations: an innovative benchmarking tool.

OBJECTIVES: The vast majority of residents' working time is spent away from patients. In hospital practice, many factors may influence the resident's working day structure.Using an innovative method, we aimed to compare working time allocation among internal medicine residents using time-motion observations. The first study goal was to describe how the method could be used for inter-hospital comparison. The secondary goal was to learn about specific differences in the resident's working day structure in university and non-university hospital settings. DESIGN: Two separate time-motion studies. Trained peer-observers followed the residents during weekday day shifts with a tablet, able to record 22 different activities and corresponding context (with patient, phone, colleague or computer). SETTING: Internal medicine residencies at a university (May-July 2015) and a non-university (September-October 2016) community hospital. PARTICIPANTS: 28 residents (mean age: 29 years, average postgraduate training: 30 months) at university hospital, 21 residents (mean age: 30 years, average postgraduate training: 17 months) at non-university hospital. OUTCOMES: Time spent with patients and time dedicated to activities directly related to patients; description of main differences of time allocation between hospitals. RESULTS: Cumulatively 1051 hours of observation (566 (university hospital)+486 (non-university hospital)) and 92 day shifts (49+43) were evaluated. Daily working time was 11.5 versus 11.3 hours. A median daily period of 195 min (IQR 179-211, 27.9%) and 116 min (IQR 98-134, 17.2%) (p<0.001) was dedicated to direct patient care, respectively. CONCLUSIONS: We successfully identified differences potentially related to each hospital structure and organisation. Inter-hospital comparisons could help set up interventions aiming to improve workday structure and experience of residents.

A high Gas6 level in plasma predicts venous thromboembolism recurrence, major bleeding and mortality in the elderly: a prospective multicenter cohort study.

Essentials Predictive ability of pro-hemostatic Gas6 for recurrent venous thromboembolism (VTE) is unknown. We measured Gas6 levels in 864 patients with VTE over 3 years. High Gas6 (> 157%) at diagnosis is associated with VTE recurrence, major bleeding and mortality. Gas6 plasma levels measured 12 months after the index VTE are discriminatory for VTE recurrence. SUMMARY: Background Growth arrest-specific gene 6 (Gas6) is a prohemostatic protein with an unknown predictive ability for recurrent venous thromboembolism (VTE). In the elderly, VTE results in higher mortality but does not have a higher rate of recurrence than in younger patients. Consequently, anticoagulation management in the elderly is challenging. Objective To prospectively investigate the performance of Gas6 in predicting VTE recurrence, major bleeding and mortality in the elderly. Methods Consecutive patients aged ≥ 65 years with acute VTE were followed for a period of 3 years. Primary outcomes were symptomatic VTE recurrence, major bleeding, and mortality. Plasma Gas6 was measured with ELISA. Results Gas6 levels were measured in 864 patients at the time of the index VTE (T1) and, in 70% of them, also 12 months later (T2). The Gas6 level at T1 was discriminatory for VTE recurrence (C-statistic, 0.56; 95% confidence interval [CI] 0.51-0.62), major bleeding (0.60, 95% CI 0.55-0.65) and mortality (0.69, 95% CI 0.65-0.73) up to 36 months. VTE recurrence up to 24 months after T2 was discriminated by the Gas6 level at T2 (0.62, 95% CI 0.54-0.71). High Gas6 levels (> 157%) and continuous Gas6 levels at T1 were associated with VTE recurrence up to 6 months and 12 months, respectively. Conclusions In elderly patients, a high Gas6 level is associated with higher risks of VTE recurrence, major bleeding, and death. These findings support further studies to assess the performance of Gas6 in adjusting the length of anticoagulation.

When your patient clicks: a loud clicking sound as a key sign to the diagnosis.

A 19-year-old male patient was referred by his general practitioner with a new 'cardiac murmur'. For 1 week, he had been able to provoke a clicking sound, which was in time with his heart beat and originated from his chest. The physical examination and laboratory tests were normal. The sound was initially interpreted as most likely due to a valve condition such as mitral valve prolapse, but a transthoracic echocardiogram was normal. A cardiac CT was obtained, which showed left-sided ventral pneumothorax.The Hamman's sign is a loud precordial pulse synchronous sound, which is often postural. It is pathognomonic for left-sided pneumothorax or pneumomediastinum. Hamman's sign as a presenting symptom is rare, but if present is key to diagnosis. The awareness of rare clinical findings is important and will prevent unnecessary diagnostic tests.

Endothelial LOX-1 activation differentially regulates arterial thrombus formation depending on oxLDL levels: role of the Oct-1/SIRT1 and ERK1/2 pathways.

AIMS: The lectin-like oxLDL receptor-1 (LOX-1) promotes endothelial uptake of oxidized low-density lipoprotein (oxLDL) and plays an important role in atherosclerosis and acute coronary syndromes (ACS). However, its role in arterial thrombus formation remains unknown. We investigated whether LOX-1 plays a role in arterial thrombus formation in vivo at different levels of oxLDL using endothelial-specific LOX-1 transgenic mice (LOX-1TG) and a photochemical injury thrombosis model of the carotid artery. METHODS AND RESULTS: In mice fed a normal chow diet, time to arterial occlusion was unexpectedly prolonged in LOX-1TG as compared to WT. In line with this, tissue factor (TF) expression and activity in carotid arteries of LOX-1TG mice were reduced by half. This effect was mediated by activation of octamer transcription factor 1 (Oct-1) leading to upregulation of the mammalian deacetylase silent information regulator-two 1 (SIRT1) via binding to its promoter and subsequent inhibition of NF-κB signaling. In contrast, intravenous injection of oxLDL as well as high cholesterol diet for 6 weeks led to a switch from the Oct-1/SIRT1 signal transduction pathway to the ERK1/2 pathway and in turn to an enhanced thrombotic response with shortened occlusion time. CONCLUSIONS: Thus, LOX-1 differentially regulates thrombus formation in vivo depending on the degree of activation by oxLDL. At low oxLDL levels LOX-1 activates the protective Oct-1/SIRT1 pathway, while at higher levels of the lipoprotein switches to the thrombogenic ERK1/2 pathway. These findings may be important for arterial thrombus formation in ACS and suggest that SIRT1 may represent a novel therapeutic target in this context.

Anticoagulation Management Practices and Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Clinical Research Study.

Whether anticoagulation management practices are associated with improved outcomes in elderly patients with acute venous thromboembolism (VTE) is uncertain. Thus, we aimed to examine whether practices recommended by the American College of Chest Physicians guidelines are associated with outcomes in elderly patients with VTE. We studied 991 patients aged ≥65 years with acute VTE in a Swiss prospective multicenter cohort study and assessed the adherence to four management practices: parenteral anticoagulation ≥5 days, INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulation, early start with vitamin K antagonists (VKA) ≤24 hours of VTE diagnosis, and the use of low-molecular-weight heparin (LMWH) or fondaparinux. The outcomes were all-cause mortality, VTE recurrence, and major bleeding at 6 months, and the length of hospital stay (LOS). We used Cox regression and lognormal survival models, adjusting for patient characteristics. Overall, 9% of patients died, 3% had VTE recurrence, and 7% major bleeding. Early start with VKA was associated with a lower risk of major bleeding (adjusted hazard ratio 0.37, 95% CI 0.20-0.71). Early start with VKA (adjusted time ratio [TR] 0.77, 95% CI 0.69-0.86) and use of LMWH/fondaparinux (adjusted TR 0.87, 95% CI 0.78-0.97) were associated with a shorter LOS. An INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulants was associated with a longer LOS (adjusted TR 1.2, 95% CI 1.08-1.33). In elderly patients with VTE, the adherence to recommended anticoagulation management practices showed mixed results. In conclusion, only early start with VKA and use of parenteral LMWH/fondaparinux were associated with better outcomes.

Immune thrombocytopenia patients requiring anticoagulation--maneuvering between Scylla and Charybdis.

Immune thrombocytopenia (ITP) is no longer a disorder of young people. Half of the patients are older than 50 and comorbidities become more common with age. Anticoagulation has to be discussed when an ITP patient develops atrial fibrillation, venous or arterial thromboembolism, myocardial infarction, or stroke. At the same time low platelet counts often prohibit therapeutic anticoagulation. Guidelines do not give guidance for these situations. This article summarizes experiences from case reports and small series and suggests an approach to ITP patients with thrombocytopenia and an indication for anticoagulation.