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.

Early Rhythm-Control Therapy in Patients with Atrial Fibrillation.

BACKGROUND: Despite improvements in the management of atrial fibrillation, patients with this condition remain at increased risk for cardiovascular complications. It is unclear whether early rhythm-control therapy can reduce this risk. METHODS: In this international, investigator-initiated, parallel-group, open, blinded-outcome-assessment trial, we randomly assigned patients who had early atrial fibrillation (diagnosed ≤1 year before enrollment) and cardiovascular conditions to receive either early rhythm control or usual care. Early rhythm control included treatment with antiarrhythmic drugs or atrial fibrillation ablation after randomization. Usual care limited rhythm control to the management of atrial fibrillation-related symptoms. The first primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome; the second primary outcome was the number of nights spent in the hospital per year. The primary safety outcome was a composite of death, stroke, or serious adverse events related to rhythm-control therapy. Secondary outcomes, including symptoms and left ventricular function, were also evaluated. RESULTS: In 135 centers, 2789 patients with early atrial fibrillation (median time since diagnosis, 36 days) underwent randomization. The trial was stopped for efficacy at the third interim analysis after a median of 5.1 years of follow-up per patient. A first-primary-outcome event occurred in 249 of the patients assigned to early rhythm control (3.9 per 100 person-years) and in 316 patients assigned to usual care (5.0 per 100 person-years) (hazard ratio, 0.79; 96% confidence interval, 0.66 to 0.94; P = 0.005). The mean (±SD) number of nights spent in the hospital did not differ significantly between the groups (5.8±21.9 and 5.1±15.5 days per year, respectively; P = 0.23). The percentage of patients with a primary safety outcome event did not differ significantly between the groups; serious adverse events related to rhythm-control therapy occurred in 4.9% of the patients assigned to early rhythm control and 1.4% of the patients assigned to usual care. Symptoms and left ventricular function at 2 years did not differ significantly between the groups. CONCLUSIONS: Early rhythm-control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with early atrial fibrillation and cardiovascular conditions. (Funded by the German Ministry of Education and Research and others; EAST-AFNET 4 ISRCTN number, ISRCTN04708680; ClinicalTrials.gov number, NCT01288352; EudraCT number, 2010-021258-20.).

Use, Persistence, Efficacy, and Safety of Apixaban in Patients with Non-Valvular Atrial Fibrillation in Unselected Patients in Germany. Results of the Prospective Apixaban in Atrial Fibrillation (APAF) Registry.

INTRODUCTION: Apixaban has been shown to be superior to warfarin in patients with non-valvular atrial fibrillation in the randomized ARISTOTLE trial and its use is recommended in current guidelines. There are only scarce data about its use, efficacy, and safety in unselected patients in Germany. METHODS AND RESULTS: The APAF registry is a prospective non-interventional study enrolling 5015 patients with non-valvular atrial fibrillation. Of these, 1349 (26.9%) patients were initially treated with apixaban and followed up at 3 and 12 months. The dose of apixaban used was 1 × 2.5 mg in 1.6%, 2 × 2.5 mg in 30.4%, and 2 × 5 mg daily in 68.0% of patients, respectively. Inappropriate underdosing of apixaban was observed in 22.3%, mostly in elderly patients with higher HAS-BLED Score and a history of bleeding. Persistence to apixaban after 1 year was 88.6%, while the dose was changed in 3.7% of patients. Switching to other NOACs or VKAs occurred in 5.1%. After 12 months, all-cause mortality was 5.0%, non-fatal stroke occurred in 0.4%, non-fatal myocardial infarction in 0.6%, ISTH major bleeding in 0.8%, moderate or minor bleeding in 4.3% of patients, respectively. CONCLUSIONS: In this prospective experience in unselected patients with atrial fibrillation, persistence to apixaban was high, and efficacy and safety were comparable to the results in clinical trials, supporting its use in clinical practice.

Prevalence and clinical impact of iron deficiency and anaemia among outpatients with chronic heart failure: The PrEP Registry.

BACKGROUND: Iron deficiency (ID) and anaemia are common in heart failure (HF). The prospective, observational PReP registry (Prävalenz des Eisenmangels bei Patienten mit Herzinsuffizienz) studied prevalence and clinical impact of ID and anaemia in HF outpatients attending cardiology practices in Germany. METHODS AND RESULTS: A total of 42 practices enrolled consecutive patients with chronic HF [left ventricular ejection fraction (LVEF) ≤45%]. ID was defined as serum ferritin <100 µg/l, or serum ferritin ≥100 µg/l/<300 µg/l plus transferrin saturation <20%, and anaemia as haemoglobin <13 g/dl (12 g/dl) in men (women). Exercise capacity was assessed using spiroergometry (69.4%) or 6-min walk test (30.4%). Amongst 1198 PReP-participants [69.0 ± 10.6 years, 25.3% female, New York Heart Association (NYHA) class 2.4 ± 0.5, LVEF 35.3 ± 7.2%], ID was found in 42.5% (previously unknown in all), and anaemia in 18.9% (previously known in 4.8%). ID was associated with female gender, lower body weight and haemoglobin, higher NYHA class and natriuretic peptide (NP) levels (all p < 0.05). ID was also more common in anaemic than non-anaemic patients (p < 0.0001), and 9.8% of PrEP-participants had both, ID and anaemia. On spiroergometry, ID independently predicted maximum exercise capacity even after multivariable adjustment, including anaemia (p = 0.0004). In all PrEP-participants, ID predicted reduced physical performance (adjusted for age, gender, anaemia, serum creatinine, C-reactive protein, LVEF, and NP level). CONCLUSIONS: Despite high prevalence, ID was previously unknown in all PrEP-participants, and anaemia was often unappreciated. Given the clinical relevance, treatability, and independent association with reduced physical performance, ID should be considered more in real-world ambulatory healthcare settings and ID-screening be advocated to cardiologists in such populations.