Baseline Characteristics and 3-Year Outcome of Nonvalvular Atrial Fibrillation Patients Treated with the Four Direct Oral Anticoagulants (DOACs).

Direct oral anticoagulants (DOACs) represent the cornerstone therapy for cardioembolic events prevention in patients with nonvalvular atrial fibrillation (NVAF). In practice, the choice of one DOAC over another is guided by the decision-making process of the physician, which considers specific patient and drug characteristics. This study aimed to evaluate the clinical features and long-term outcomes of a real-world population treated with DOACs, where the use of the 4 different DOACs is quite equal. We conducted a retrospective observational, single-center, multidisciplinary study enrolling consecutive NVAF patients treated with one of the 4 DOACs. From an initial number of 753 patients, we excluded 72 patients because of loss to follow-up, at the end we enrolled 681:174 (23%) treated with dabigatran, 175 (23%) with apixaban, 190 (25%) with rivaroxaban, and 214 (29%) with edoxaban. Patients treated with apixaban were significantly older, more women represented (p <0.001), and with a higher cardioembolic and bleeding risk (p <0.001). Dabigatran was preferred in patients with liver failure (p = 0.008), whereas Apixaban and Edoxaban were chosen in chronic kidney disease (p = 0.002). At 3-year follow-up, 20 patients (2.7%) experienced a systemic thromboembolic event without significant differences in the 4 DOACs. In the same period, an International Society of Thrombosis and Hemostasis classification major bleeding event occurred in 26 patients (3.6%), more statistically correlated to edoxaban (6.1%) (p = 0.038). Thromboembolic events or major bleeding were higher in the edoxaban group (10%) compared with the others (p = 0.014). In our single-center real-world experience, the choice of the DOAC for a patient with NVAF was tailored to specific clinical features and drug pharmacokinetics of the patient. As a result, a small number of adverse events were observed.

Safety and efficacy of direct oral anticoagulants (DOACs) in very elderly patients (≥85 years old) with non-valvular atrial fibrillation.

BACKGROUND: Limited real-world data are available regarding the comparison about safety and efficacy of DOACs prescription in very elderly patients (≥85 years) with non-valvular atrial fibrillation (NVAF). Concern about the risk of bleeding with anticoagulation in very older patients still represents an important challenge for clinicians. The aim of this study was to evaluate the different prevalence of major bleeding and thromboembolic events between very elderly NVAF patients (≥85 years) compared to those non very elderly (<85 years). METHODS: Single center multidisciplinary registry including NVAF patients treated with DOACs. Primary safety endpoint was 2-year rate of major bleeding. Primary efficacy endpoint was 2-year rate of thromboembolic events. Event-free survival curves among groups were compared using Cox-Mantel Test. RESULTS: 908 NVAF consecutive patients were included, of these, 805 patients were <85 years (89%) and 103 patients were very elderly patients with ≥85 years (11%). Compared to patients <85 years, those very elderly have higher CHA2DS2-VASc Score (P=0.001), higher rate of hypertension (P=0.001), diabetes mellitus (P=0.030), previous bleeding events (P<0.001), previous stroke/TIA/SE (P≤0.001), heart failure (P≤0.001), and lower creatinine clearance (P<0.001). In terms of safety endpoints (overall ISTH-major bleeding) no significative difference between two groups (P=0.952) were observed up to 2-year follow-up. Systemic thromboembolic event (primary efficacy endpoint) was significantly higher in patients with ≥85 years (P=0.027). The incidence of all-cause death was significantly higher in very elderly patients (P<0.001). CONCLUSIONS: This single center registry, showed that the use of DOACs in very elderly NVAF was safe and is a therapeutic option to be pursued for stroke prevention especially for those who are at high risk of ischemic events.

Direct oral anticoagulants in patients with nonvalvular atrial fibrillation and extreme body weight.

BACKGROUND: Limited clinical data exist describing the use of direct oral anticoagulants (DOACs) in patient with extreme body weight. Thus, the International Society of Thrombosis and Haemostasis (ISTH) recommends avoiding DOACs in patients with weight >120 Kg, and on the contrary, no restrictions exist for underweight patients. OBJECTIVE: To evaluate the effects of extreme body weight on DOAC activity and to compare the clinical outcomes of patients with an extreme body weight versus patients with a normal weight (61-119 Kg) treated with DOACs. METHODS: Single tertiary care Italian centre multidisciplinary registry including nonvalvular atrial fibrillation (NVAF) patients treated with DOACs. Based on weight, three subcohorts were defined: (i) underweight patients (≤60 Kg); (ii) patients with a normal weight (61-119 Kg, as control group); and (iii) overweight patients (≥120 Kg). Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox-Mantel test. RESULTS: 812 NVAF patients were included, 108 patients weighed ≤60 Kg (13%, underweight), 688 weighed between 61 and 119 Kg (85%, normal weight), and 16 weighed ≥120 Kg (2%, overweight). In particular, among underweight patients, dabigatran was prescribed in 26% patients, apixaban in 27%, rivaroxaban in 28% and edoxaban in 22% ones. Instead, among overweight patients, 44% were treated with dabigatran, 25% with apixaban, 25% with rivaroxaban and 4% with edoxaban. Underweight patients were older, more frequently women, with lower creatinine clearance and a history of previous strokes, resulting in higher CHA2DS2-VASc score than in both remaining groups. Up to 2 years, no statistically significant difference was observed between the three groups of weight for thromboembolic events (P = .765) and for overall bleeding (P = .125), but a trend towards decreased overall bleeding rates was noticed as weight increased (24.1% vs 16.7% vs 12.5%, respectively). CONCLUSION: In this tertiary care centre registry, 15% of patients treated with DOACs presented an extreme weight. Compared to patients with a normal weight, no significant rates of thromboembolic events were observed for underweight or overweight patients. A trend towards decreased overall bleeding frequency as weight increased was highlighted up to 2 years. The present results should be considered as preliminary and hypothesis generating.

Inappropriate dose of nonvitamin-K antagonist oral anticoagulants: prevalence and impact on clinical outcome in patients with nonvalvular atrial fibrillation.

BACKGROUND: Limited real-world data are available regarding the outcome of patients treated with inappropriate dose of nonvitamin-K antagonist oral anticoagulants (NOACs). OBJECTIVE: To assess the prevalence and factors associated with inappropriate dose prescription of NOACs and to evaluate adverse events that come from this inappropriate prescription. METHODS: Single-center multidisciplinary registry including nonvalvular atrial fibrillation patients treated with NOACs. Based on guidelines criteria for dose reduction, two subcohorts were defined as treated with appropriate or inappropriate NOACs dose. Primary efficacy endpoint was 2-year rate of thromboembolic events. Primary safety endpoint was 2-year rate of major bleeding. Event-free survival curves among groups were compared using Cox-Mantel test. RESULTS: A total of 760 nonvalvular atrial fibrillation patients were included; 32% patients were treated with dabigatran, 34% with apixaban, 24% with rivaroxaban and 10% with edoxaban. An inappropriate dose was prescribed in 96 patients (12.6%), and in most cases (68%) it was too low. Rivaroxaban (15%) and apixaban (18.5%) were the most frequently prescribed with an inappropriate dose. Patients treated with an inappropriate dose were elderly people, with low-creatinine clearance value, who had experienced previous bleeding and with a high CHADS2 VASc score. In 2 years, a trend for higher numbers of thromboembolic events (5.2 vs. 3.3%, P = 0.348) and less major bleeding (2.1 vs. 4.2%, P = 0.316) has been observed in patients with inappropriate NOACs prescriptions. CONCLUSION: Nearly 13% of patients were treated with an inappropriate dose of NOACs, in this single-center study. A trend for higher numbers of thromboembolic events was observed in these patients. The results should be considered as hypothesis generating.

Real-world 2-year outcome of atrial fibrillation treatment with dabigatran, apixaban, and rivaroxaban in patients with and without chronic kidney disease.

Patients with non-valvular atrial fibrillation (NVAF) and chronic kidney disease (CKD) are at increased risk of stroke and bleeding. Although direct oral anticoagulant (DOAC) trials excluded patients with severe CKD, a growing portion of CKD patients have been starting DOACs and limited data from real-world outcome in this high-risk setting are available. The INSigHT registry included 632 consecutive NVAF patients that started apixaban (256 patients, 41%), dabigatran (245, 39%) and rivaroxaban (131, 20%) between 2012 and 2015. Based on creatinine clearance, two sub-cohorts were defined: (1) non-CKD group (CrCl 60-89 mL/min, 413 patients) and (2) CKD group (15-59 ml/min, 219). Compared to non-CKD patients, those with CKD, were at higher ischemic (CHA2DS2-VASc 4.5 vs 2.9, p < 0.001) and hemorrhagic risk (HAS-BLED 2.4 vs 1.8, p < 0.001). At 2-year follow-up, the overall ISTH-major bleeding and thromboembolic event rates were 5.2% and 2.3% and no significant difference between non-CKD and CKD patients for both efficacy and safety endpoints were observed. In non-CKD patients, the 2-year ISTH-major bleeding rates were higher in rivaroxaban group (HR 2.9, 95% CI 1.1-7.3; p = 0.047) while dabigatran showed non-significant excess in thromboembolic events (HR 4.3, 95% CI 0.9-20.8; p = 0.068). In CKD patients, a significantly higher rate of thromboembolic events was observed in rivaroxaban (HR 6.3, 95% CI 1.1-38.1; p = 0.044). This real-world, non-insurance database registry shows remarkable 2-year safety and efficacy profile of DOACs even in patients with moderate to severe CKD. Head to head differences between DOACs are exploratory, hypothesis generating and warrant further investigation in larger studies.