Heavy menstrual bleeding in women on anticoagulant treatment for venous thromboembolism: Comparison of high- and low-dose rivaroxaban with aspirin

Contains fulltext : 232761.pdf (Publisher’s version ) (Open Access)BACKGROUND: Rivaroxaban may induce heavy menstrual bleeding. It is unknown if this effect is dose related or if rivaroxaban is associated with more menstrual bleeding than aspirin. OBJECTIVES: To demonstrate and compare menstrual patterns and actions taken among women receiving aspirin and two doses of rivaroxaban. METHODS: The EINSTEIN-CHOICE trial compared once-daily rivaroxaban 20 mg, rivaroxaban 10 mg, and aspirin 100 mg for extended treatment of venous thromboembolism in patients who had completed 6 to 12 months of anticoagulant therapy. In 362 women with menstrual cycles, menstrual flow duration and intensity assessed at days 30, 90, 180, and 360 were compared with those before starting anticoagulant therapy. RESULTS: Menstrual flow duration increased in 12%-18% of the 134 women given 20-mg rivaroxaban, in 6% to 12% of 120 women given 10-mg rivaroxaban, and in 9% to 12% of 108 women given aspirin. Corresponding increases in flow intensity were 19% to 24%, 14% to 21%, and 13% to 20%. The odds ratios (ORs) for increased menstrual flow duration were 1.36 (95% confidence interval [CI], 0.62-2.96) for rivaroxaban 20 mg versus aspirin, 0.77 (95% CI, 0.33-1.81) for rivaroxaban 10 mg versus aspirin, and 0.57 (95% CI, 0.26-1.25) for rivaroxaban 10 mg versus 20 mg. The ORs for increased menstrual flow intensity were 1.41 (95% CI, 0.67-2.99), 1.07 (95% CI, 0.49-2.34), and 0.76 (95% CI, 0.37- 1.57), respectively. CONCLUSIONS: There were no statistically significant differences in menstrual hemorrhage patterns between women treated with 10 or 20 mg of rivaroxaban and aspirin. Compared with 10-mg rivaroxaban or aspirin, 20-mg rivaroxaban showed numerically more often increased menstrual flow duration and intensity

Use of Prestudy Heparin Did Not Influence the Efficacy and Safety of Rivaroxaban in Patients Treated for Symptomatic Venous Thromboembolism in the EINSTEIN DVT and EINSTEIN PE Studies

Objectives: In the EINSTEIN DVT and EINSTEIN PE studies, the majority of patients received heparins to bridge the period during venous thromboembolism (VTE) diagnosis confirmation and the start of the study. In contrast to vitamin K antagonists (VKAs), rivaroxaban may not require initial heparin treatment. Methods: To evaluate the effect of prestudy heparin on the efficacy and safety of rivaroxaban relative to enoxaparin/VKA, the 3-month incidence of recurrent VTE, and the 14-day incidence of major and non-major clinically relevant bleeding were compared in patients who did and did not receive prestudy heparin. Results: Of the 8,281 patients randomized, 6,937 (83.8%) received prestudy heparin (mean +/- SD duration = rivaroxaban: 1.04 [+/- 0.74] days; enoxaparin 1.03 [+/- 0.42] days), and 1,344 (16.2%) did not. In patients who did not receive prestudy heparin, the incidences of recurrent VTE were similar in rivaroxaban (15 of 649, 2.3%) and enoxaparin/VKA (13 of 695, 1.9%) patients (adjusted hazard ratio [HR] = 1.11; 95% confidence interval [CI] = 0.52 to 2.37). The incidences of recurrent VTE were also similar in rivaroxaban (54 of 3,501, 1.5%) and enoxaparin/VKA (69 of 3,436, 2.0%) patients who did receive prestudy heparin (adjusted HR = 0.74; 95% CI = 0.52 to 1.06; pinteraction = 0.32). The incidences of major or nonmajor clinically relevant bleeding with rivaroxaban were not significantly different from those with enoxaparin/VKA, either with (105 of 3,485, 3.0% vs. 104 of 3,428, 3.0%; adjusted HR = 0.98; 95% CI = 0.75 to 1.29) or without (24 of 645, 3.7% vs. 30 of 688, 4.4%; adjusted HR = 0.81; 95% CI = 0.46 to 1.40; pinteraction = 0.68) prestudy heparin. Conclusions: Although the majority of patients in the EINSTEIN studies received prestudy heparin, there were no notable differences in treatment effect of rivaroxaban versus enoxaparin/VKA in those who did and did not receive it. (C) 2015 by the Society for Academic Emergency Medicin

Safety and efficacy of the partial adenosine A1 receptor agonist neladenoson bialanate in patients with chronic heart failure with reduced ejection fraction: a phase IIb, randomized, double-blind, placebo-controlled trial

Aims Neladenoson bialanate is a partial adenosine A1 receptor agonist with demonstrated beneficial effects on cardiac function in animal models. We aimed to assess the dose-response effect of neladenoson bialanate on cardiac structure and function, clinical outcome, and safety in patients with heart failure (HF) with reduced ejection fraction (HFrEF).Methods and results PANTHEON was a dose-finding, phase IIb, randomized, double-blind, placebo-controlled trial conducted in 92 centres in 11 countries including 462 patients with chronic HFrEF, randomized to once daily oral dose of neladenoson bialanate (5, 10, 20, 30, and 40mg) or placebo. The primary endpoints were change from baseline to 20weeks in left ventricular ejection fraction (LVEF) (echocardiography) and in N-terminal pro-B-type natriuretic peptide (NT-proBNP). Mean age of the patients was 67 years, 17% were female, mean LVEF was 28%, mean NT-proBNP was 2085 ng/L. After 20weeks of treatment, there was no dose-effect of neladenoson bialanate on changes in NT-proBNP or LVEF (primary endpoints). No effect of neladenoson bialanate was found on left ventricular volumes, high-sensitivity troponin T, or cardiovascular mortality, HF hospitalization, and urgent visits for HF (secondary endpoints). There was a dose-dependent increase in creatinine and cystatin C, and a dose-dependent decrease in estimated glomerular filtration rate and heart rate.Conclusions In patients with chronic HFrEF, treatment with neladenoson bialanate was not associated with dose-dependent favourable effects on cardiac structure and function, cardiac risk markers, or clinical outcome but was associated with a dose-dependent decrease in renal function.Clinical Trial Registration: ClinicalTrials.gov Identifier NCT02992288.Cardiolog

Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.

Contains fulltext : 219893.pdf (Publisher’s version ) (Closed access)BACKGROUND: Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. METHODS: In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children /=1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. FINDINGS: From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87-95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29-35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0.40, 95% CI 0.11-1.41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0.012). Major or clinically relevant non-major bleeding in participants who received >/=1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1.58, 95% CI 0.51-6.27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. INTERPRETATION: In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. FUNDING: Bayer AG and Janssen Research & Development.1 januari 202