Impact of body mass index on real-world outcomes of rivaroxaban treatment in Japanese patients with non-valvular atrial fibrillation.

This sub-analysis of the XAPASS, a prospective, single-arm, observational study, aimed to evaluate relationships between body mass index (BMI) and safety (major bleeding and all-cause mortality) and effectiveness [stroke/non-central nervous system (non-CNS) systemic embolism (SE)/myocardial infarction (MI)] outcomes in Japanese patients with non-valvular atrial fibrillation (NVAF) receiving rivaroxaban. Patients were categorized according to BMI (kg/m2) as underweight (< 18.5), normal weight (18.5 to < 25), overweight (25 to < 30), or obese (≥ 30). In total, 9578 patients with NVAF completed the 1-year follow-up and were evaluated; of these, 7618 patients had baseline BMI data. Overall, 542 (5.7%), 4410 (46.0%), 2167 (22.6%), and 499 (5.2%) patients were underweight, normal weight, overweight, and obese, respectively. Multivariable Cox regression analysis demonstrated that none of the BMI categories were independent predictors of major bleeding whereas being underweight was independently associated with increased all-cause mortality [hazard ratio (HR) 3.56, 95% confidence interval (CI) 2.40-5.26, p < 0.001]. The incidence of stroke/non-CNS SE/MI was higher in patients who were underweight than in those of normal weight (HR 2.11, 95% CI 1.20-3.70, p = 0.009). However, in multivariable analyses, being underweight was not identified as an independent predictor of stroke/non-CNS SE/MI (HR 1.64, 95% CI 0.90-2.99, p = 0.104). In conclusion, the high incidence of thromboembolic events and all-cause mortality in patients who were underweight highlights that thorough evaluation of disease status and comorbidities may be required in this population.

Real-world outcomes of rivaroxaban treatment in elderly Japanese patients with nonvalvular atrial fibrillation.

Direct oral anticoagulants (DOACs), such as rivaroxaban, reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). However, it is still unclear whether the stroke reduction benefit outweighs the bleeding risk in elderly Japanese patients with NVAF. The Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) was a real-world, prospective observational, post-marketing surveillance study on the safety and effectiveness of rivaroxaban in Japanese clinical practice. This sub-analysis evaluated the clinical outcomes of elderly patients aged ≥ 75 years. At the 1-year follow-up, there were 4,685 (48.91%) and 4,893 (51.09%) patients aged ≥ 75 and < 75 years, respectively. Safety and effectiveness outcomes were compared between patients aged ≥ 75 years and those aged < 75 years, and among 3 elderly sub-populations (age ranges: 75-79, 80-84, and ≥ 85 years). Patients aged ≥ 75 years had higher rates of major bleeding [2.22 vs. 1.35 events per 100 patient-years, hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.17-2.28] and composite of stroke (ischemic or hemorrhagic)/non-central nervous system (non-CNS) systemic embolism (SE)/myocardial infarction (MI) (2.41 vs. 1.21 events per 100 patient-years, HR 1.97, 95% CI 1.40-2.77) compared to patients aged < 75 years. Intracranial hemorrhage rates were < 1 event per 100 patient-years in both groups (0.85 vs. 0.59 events per 100 patient-years, HR 1.43, 95% CI 0.85-2.40). Kaplan-Meier curves of major bleeding and stroke/non-CNS SE/MI showed that no significant differences of cumulative event rates were identified among the 3 elderly sub-populations. Stepwise Cox regression analyses revealed that creatinine clearance (CrCl) (<50 mL/min), hepatic impairment, and hypertension were specific predictors for major bleeding and no specific predictors were found for stroke/non-CNS SE/MI in patients aged ≥ 75 years. In conclusion, safety and effectiveness event rates were higher in patients aged ≥ 75 years compared with those aged < 75 years, yet, no distinct differences were observed among the 3 elderly sub-populations.

Real-World Outcomes of Rivaroxaban Treatment in Patients with Both Nonvalvular Atrial Fibrillation and a History of Ischemic Stroke/Transient Ischemic Attack.

INTRODUCTION: Prior stroke is a risk factor for stroke and bleeding during anticoagulation in patients with atrial fibrillation (AF). Although rivaroxaban is widely prescribed to reduce their risk of stroke in patients with nonvalvular AF (NVAF), the real-world evidence on rivaroxaban treatment is limited. We aimed to examine the outcomes of rivaroxaban treatment in NVAF patients with prior ischemic stroke/transient ischemic attack (TIA) by using the data of the Xarelto Post-Authorization Safety and Effectiveness Study in Japanese -Patients with AF, a prospective, single-arm, observational study. METHODS: The clinical outcomes of 9,578 patients who completed the 1-year follow-up were evaluated. Safety and effectiveness outcomes were compared between patients with and without prior ischemic stroke/TIA. RESULTS: Among the patients, 2,153 (22.5%) had prior ischemic stroke/TIA. They were significantly older and had lower body weight, lower creatinine clearance, higher CHADS2, CHA2DS2-VASc, and modified HAS-BLED scores as compared to those without prior ischemic stroke/TIA. Any bleeding (9.1 vs. 7.2 events per 100 patient-years), major bleeding (2.3 vs. 1.6 events per 100 patient-years), and stroke/non-central nervous system systemic embolism/myocardial infarction (3.4 vs. 1.3 events per 100 patient-years) were more frequent in patients with prior ischemic stroke/TIA. Stepwise regression analysis suggested that body weight of ≤50 kg and diabetes mellitus were predictive of major bleeding in patients with prior ischemic stroke/TIA. CONCLUSIONS: Safety and effectiveness event rates were higher in patients with prior ischemic stroke/TIA than those without. This might be explained by differences in several risk profiles including age, body weight, renal function, and risk scores such as CHADS2 between the groups. Clinicaltrials.gov: NCT01582737.

Real-world outcomes of rivaroxaban treatment in patients with nonvalvular atrial fibrillation and worsening renal function.

BACKGROUND: Rivaroxaban is a direct oral anticoagulant administered to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). The Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) was a prospective, observational, post-marketing surveillance study that examined the safety and effectiveness of rivaroxaban in routine clinical practice. This sub-analysis of the XAPASS investigated the outcomes of patients with worsening renal function (WRF). METHODS: The XAPASS included 11,308 patients with NVAF who began treatment with rivaroxaban. Of 9578 patients who completed 1-year follow-up, the 7509 patients, for whom the change in creatinine clearance could be assessed, were included in the present analysis. Patients with WRF were those with a decrease in creatinine clearance of ≥20% from enrollment to any time point; patients with stable renal function (SRF) were those without such a decrease. Outcomes in patients with WRF versus SRF were compared at 1 year. RESULTS: We identified 1229 patients with WRF and 6280 patients with SRF. Patients with WRF were older and had higher mean CHADS2 and modified HAS-BLED scores compared to patients with SRF. The incidence rates of any bleeding (hazard ratio: 1.12; 95% confidence interval: 0.88-1.41), major bleeding (1.20; 0.75-1.90), and the composite endpoint stroke/systemic embolism/myocardial infarction (1.06; 0.65-1.71) were similar between the two groups. CONCLUSIONS: No association between WRF and occurrence of any bleeding, major bleeding, and stroke/systemic embolism/myocardial infarction was observed in patients with AF on rivaroxaban treatment during 1-year follow-up in real-world clinical practice. Clinicaltrials.gov: NCT01582737.

Design and baseline characteristics of the Xarelto Post-Authorization Safety & Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS).

Background: The phase III Japanese Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (J-ROCKET AF) showed that the rivaroxaban group had a lower event rate of intracranial bleeding than the warfarin group and that rivaroxaban was noninferior to warfarin for the principal safety outcome. However, safety and effectiveness data from unselected patients with AF in everyday clinical practice in Japan are lacking. Methods: The Xarelto Post-Authorization Safety & Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) is a real-world, prospective, single-arm, observational study mandated by the Japanese authority as postmarketing surveillance. XAPASS involves patients with nonvalvular AF prescribed rivaroxaban. The principal safety outcome is a composite of major and nonmajor bleeding events, and the primary effectiveness outcome is the incidence of ischemic stroke, hemorrhagic stroke, noncentral nervous system systemic embolism, and myocardial infarction. Results: In total, 11 308 patients were enrolled from April 2012 to June 2014. Their age was 73.1 ± 9.9 years, and their CHADS 2 score was 2.2 ± 1.3. Female patients, patients aged ≥75 years, patients with a body weight of ≤50 kg, and patients with a creatinine clearance of <50 mL/min constituted 38.1%, 48.7%, 19.5%, and 23.9% of all patients, respectively. Almost half (53.2%) of patients were prescribed other anticoagulants before starting rivaroxaban. Conclusions: Data from this study will supplement those from the J-ROCKET AF and provide practical information for the optimal use of rivaroxaban for stroke prevention in Japanese patients with AF (Clinicaltrials.gov: NCT01582737).

Effect of cervical vagal nerve stimulation on defibrillation energy: a possible adjunct to efficient defibrillation.

The efficacy of electrical defibrillation is considered to be related to the autonomic status. In search of a possible adjunct to enhance the therapeutic performance of an implantable cardioverter-defibrillator. we investigated whether parasympathetic manipulation by cervical vagal nerve stimulation (VNS) increases defibrillation efficacy. The effects of VNS on transcardiac defibrillation threshold (DFT) were assessed in 55 anesthetized dogs. In neurally intact dogs, right and left unilateral VNS at 10 mA for 7 seconds significantly decreased the DFT after 10 seconds of ventricular fibrillation (control: 3.1 +/- 0.9 J, right: 2.1 +/- 0.9 J [delta-35 +/- 12%, P < 0.0001], left: 2.2 +/- 0.8 J [delta-31 +/- 11%, P < 0.0005]), while bilateral VNS did not (2.8 +/- 1.0 J). In dogs with decentralized vagus nerves, both unilateral and bilateral VNS decreased the DFT. The extent of the VNS-induced decrease in DFT was dependent on the current and the duration of stimulation. We conclude that unilateral VNS decreases the DFT, while bilateral VNS paradoxically has no effect on the DFT unless the vagi are decentralized.