Rivaroxaban Monotherapy vs Combination Therapy With Antiplatelets on Total Thrombotic and Bleeding Events in Atrial Fibrillation With Stable Coronary Artery Disease: A Post Hoc Secondary Analysis of the AFIRE Trial.

Importance: Appropriate regimens of antithrombotic therapy for patients with atrial fibrillation (AF) and coronary artery disease (CAD) have not yet been established. Objective: To compare the total number of thrombotic and/or bleeding events between rivaroxaban monotherapy and combined rivaroxaban and antiplatelet therapy in such patients. Design, Setting, and Participants: This was a post hoc secondary analysis of the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) open-label, randomized clinical trial. This multicenter analysis was conducted from February 23, 2015, to July 31, 2018. Patients with AF and stable CAD who had undergone percutaneous coronary intervention or coronary artery bypass grafting 1 or more years earlier or who had angiographically confirmed CAD not requiring revascularization were enrolled. Data were analyzed from September 1, 2020, to March 26, 2021. Interventions: Rivaroxaban monotherapy or combined rivaroxaban and antiplatelet therapy. Main Outcomes and Measures: The total incidence of thrombotic, bleeding, and fatal events was compared between the groups. Cox regression analyses were used to estimate the risk of subsequent events in the 2 groups, with the status of thrombotic or bleeding events that had occurred by the time of death used as a time-dependent variable. Results: A total of 2215 patients (mean [SD] age, 74 [8.2] years; 1751 men [79.1%]) were included in the modified intention-to-treat analysis. The total event rates for the rivaroxaban monotherapy group (1107 [50.0%]) and the combination-therapy group (1108 [50.0%]) were 12.2% (135 of 1107) and 19.2% (213 of 1108), respectively, during a median follow-up of 24.1 (IQR, 17.3-31.5) months. The mortality rate was 3.7% (41 of 1107) in the monotherapy group and 6.6% (73 of 1108) in the combination-therapy group. Rivaroxaban monotherapy was associated with a lower risk of total events compared with combination therapy (hazard ratio, 0.62; 95% CI, 0.48-0.80; P < .001). Monotherapy was an independent factor associated with a lower risk of subsequent events compared with combination therapy. The mortality risk after a bleeding event (monotherapy, 75% [6 of 8]; combination therapy, 62.1% [18 of 29]) was higher than that after a thrombotic event (monotherapy, 25% [2 of 8]; combination therapy, 37.9% [11 of 29]). Conclusions and Relevance: Rivaroxaban monotherapy was associated with lower risks of total thrombotic and/or bleeding events than combination therapy in patients with AF and stable CAD. Tapered antithrombotic therapy with a sole anticoagulant should be considered in these patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02642419.

Changes in self-reported physical activity and health-related quality of life following 3-month astaxanthin supplementation in patients with heart failure: results from a pilot study.

BACKGROUND: Astaxanthin has a strong antioxidant effect. We recently demonstrated that following 3-month astaxanthin supplementation, cardiac contractility and exercise tolerance improved, possibly through the suppression of oxidative stress in a small pilot study involving patients with heart failure with left ventricular systolic dysfunction. This is a sub-study of our pilot study to investigate whether improvements of selfreported physical activity and health-related quality of life were observed following 3-month astaxanthin supplementation. METHODS: We investigated the changes in physical activity by the Specific Activity Scale score and healthrelated quality of life by physical and mental component summary scores in Short Form-8 at baseline and after 3-month astaxanthin supplementation. RESULTS: Data from 17 patients with heart failure were assessed. Following 3-month astaxanthin supplementation, the Specific Activity Scale score increased from the median of 4.5 (interquartile range, 2.0) to 6.5 (interquartile range, 1.1) metabolic equivalent (P=0.001), and the physical and mental component summary scores increased from 46.1±9.2 to 50.8±6.8 (P=0.015) and from 48.9±9.1 to 53.8±4.8 (P=0.022), respectively. There was a linear relationship of the baseline heart rate, or mental component summary score with the percent change in the Specific Activity Scale score (r=0.523, P=0.031 and r=-0.505, P=0.039, respectively). In addition, there was a direct relationship of ischemic etiology with the percent change in the physical component summary score (r=0.483, P=0.049, respectively). Finally, there was a linear relationship between the percent change in the Specific Activity Scale score and that in the mental component summary score (r=0.595, P=0.012). CONCLUSIONS: Following 3-month astaxanthin supplementation, improvements of the self-reported physical activity level and health-related quality of life in both mental and physical components were observed. In patients with heart failure, those with higher baseline heart rate, ischemic etiology, and poorer baseline health-related quality of life have potentials to have greater improvement of physical activity and/or health-related quality of life.

Effects of 3-Month Astaxanthin Supplementation on Cardiac Function in Heart Failure Patients with Left Ventricular Systolic Dysfunction-A Pilot Study.

Astaxanthin has strong antioxidant properties. We conducted a prospective pilot study on heart failure (HF) patients with left ventricular (LV) systolic dysfunction to investigate improvements in cardiac function and exercise tolerance in relation to suppression of oxidative stress by 3-month astaxanthin supplementation. Oxidative stress markers-serum Diacron reactive oxygen metabolite (dROM), biological antioxidant potential (BAP), and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations, LV ejection fraction (LVEF), and 6-min walk distance (6MWD) were assessed before and after 3-month astaxanthin supplementation. Finally, the data of 16 HF patients were analyzed. Following 3-month astaxanthin supplementation, dROM level decreased from 385.6 ± 82.6 U.CARR to 346.5 ± 56.9 U.CARR (p = 0.041) despite no changes in BAP and urinary 8-OHdG levels. LVEF increased from 34.1 ± 8.6% to 38.0 ± 10.0% (p = 0.031) and 6MWD increased from 393.4 ± 95.9 m to 432.8 ± 93.3 m (p = 0.023). Significant relationships were observed between percent changes in dROM level and those in LVEF. In this study, following 3-month astaxanthin supplementation, suppressed oxidative stress and improved cardiac contractility and exercise tolerance were observed in HF patients with LV systolic dysfunction. Correlation between suppression of oxidative stress and improvement of cardiac contractility suggests that suppression of oxidative stress by astaxanthin supplementation had therapeutic potential to improve cardiac functioning.

Adaptive servo-ventilation in cardiac function and neurohormonal status in patients with heart failure and central sleep apnea nonresponsive to continuous positive airway pressure.

OBJECTIVES: The aim of this study was to investigate whether effective suppression of central sleep apnea (CSA) by adaptive servo-ventilation (ASV) improves underlying cardiac dysfunction among patients with heart failure (HF) in whom CSA was not effectively suppressed by continuous positive airway pressure (CPAP). BACKGROUND: The presence of CSA in HF is associated with a poor prognosis, whereas CPAP treatment improves HF. However, in a large-scale trial, CPAP failed to improve survival, probably due to insufficient CSA suppression. Recently, ASV was reported as the most effective alternative to CSA suppression. However, the effects of sufficient CSA suppression by ASV on cardiac function are unknown. METHODS: Patients with New York Heart Association class ≥II HF, left ventricular ejection fraction <50%, and CSA that was unsuppressed (defined as an apnea-hypopnea index ≥15) despite ≥3 months of CPAP were randomly assigned to receive ASV in either CPAP mode or ASV mode. RESULTS: Of 23 patients enrolled, 12 were assigned to the ASV-mode group and 11 were assigned to the CPAP-mode group. Three months after randomization, the ASV mode was significantly more effective in suppressing the apnea-hypopnea index (from 25.0 ± 6.9 events/h to 2.0 ± 1.4 events/h; p < 0.001) compared to the CPAP mode. Compliance was signi-ficantly greater with the ASV mode than with the CPAP mode. Improvement in left ventricular ejection fraction was greater with the ASV mode (32.0 ± 7.9% to 37.8 ± 9.1%; p < 0.001) than with the CPAP mode. CONCLUSIONS: Patients with HF and unsuppressed CSA despite receiving CPAP may receive additional benefit by having CPAP replaced with ASV. Additionally, effective suppression of CSA may improve cardiac function in HF patients.