The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Adoptive Transfer of Syngeneic Bone Marrow-Derived Cells in Mice with Obesity-Induced Diabetes : Selenoorganic Antioxidant Ebselen Restores Stem Cell Competence

There are conflicting data regarding the effects of transplantation of bone marrow-derived cells (BMDCs) on the severity of diabetes. We therefore inquired whether the competence of BMDCs is preserved on adoptive transfer into diabetic (db/db) mice and how the adoptive transfer of BMDCs affects vascular and metabolic abnormalities in these mice. Recipient db/db mice received infusions of BMDCs prepared from either db/db or non-diabetic heterozygout mice (db/m) mice and effects on endothelium-dependent relaxation, insulin sensitivity, and renal function were evaluated. Recipients of BMDCs from db/m, but not db/db donors showed better glucose control, exhibited striking improvement in endothelium-dependent relaxation in response to acetylcholine, and had partially restored renal function. Improved glucose control was due to enhanced insulin sensitivity, most likely secondary to improved vascular function. Enhanced apoptosis of endothelial progenitor cells under oxidative stress, as well as decreased endothelial progenitor cell numbers were responsible for the apparent functional incompetence of BMDCs from db/db donors. Treatment of db/db mice with Ebselen restored the resistance of both BMDCs and endothelial progenitor cells to oxidative stress, improved acetylcholine-induced vasorelaxation, and reduced proteinuria in db/db recipients of BMDC transplantation. In conclusion, infusion of BMDCs obtained from db/m donors to db/db recipient mice benefited macrovascular function, insulin sensitivity, and nephropathy. BMDCs obtained from db/db mice were functionally incompetent secondary to the increased proportion of apoptotic cells on oxidative stress challenge; their competence was restored by Ebselen therapy

Allogeneic Transplantation to Treat Therapy Related MDS and AML in Adults.

Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML) have a poor prognosis. An earlier CIBMTR analysis of allogeneic hematopoietic cell therapy (allo-HCT) (n=868, 1990-2004) showed 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%. Modern supportive care, graft versus host disease (GVHD) prophylaxis and reduced intensity conditioning (RIC) regimens have improved outcomes. Therefore, the Center for International Blood and Marrow Transplant Research (CIBMTR) analyzed 1531 allo-HCT for adults with t-MDS (n = 759) or t-AML (n = 772) performed from 2000 to 2014. Median age was 59 years (18-74) for t-MDS and 52 years (18-77) for t-AML. 24% of patient with t-MDS and 11% of patients with t-AML and had a prior autologous transplant. A myeloablative regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Non-relapse mortality (NRM) at five years was 34% (95% confidence interval (CI) 30-37) and 34% (30-37) for t-MDS and t-AML, respectively. Relapse rates at five years were 46% (43-50) and 43% (40-47), respectively. 5-year OS and DFS was 27% (23-31) and 19% (16-23) for patients with t-MDS and 25% (22-28) and 23% (20-26) for patients with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low risk t-MDS and those receiving MAC HCT during first complete remission (CR1) t-AML, but worse for those with prior autologous HCT, higher risk cytogenetics or IPSS-R score and partially matched unrelated donors (URD). Relapse remains the major cause of treatment failure with little improvement over the past two decades. These data indicate caution in recommending allo-HCT in these conditions and more effective anti-neoplastic approaches before and after allo-HCT. BACKGROUND Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML) have a poor prognosis. An earlier CIBMTR analysis of allogeneic hematopoietic cell therapy (allo-HCT) (n=868, 1990-2004) showed 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%. Modern supportive care, graft versus host disease (GVHD) prophylaxis and reduced intensity conditioning (RIC) regimens have improved outcomes. OBJECTIVES The primary objectives are OS and DFS. The secondary objectives are non-relapse mortality (NRM), relapse, GVHD rates and identifying prognostic factors for outcomes after allo-HCT. STUDY DESIGN The Center for International Blood and Marrow Transplant Research (CIBMTR) analyzed 1531 allo-HCT for adults with t-MDS (n = 759) or t-AML (n = 772) performed from 2000 to 2014. Cumulative incidence function was used to estimate relapse, NRM, acute and chronic GVHD. Kaplan-Meier estimate was used to calculate probabilities of OS and DFS. Cox proportional hazards regression model was used to estimate hazard ratio (HR) of patient / disease / transplant related factors for outcomes of interest. RESULTS The median age was 59 years (18-74) for t-MDS and 52 years (18-77) for t-AML. 24% of patient with t-MDS and 11% of patients with t-AML and had a prior autologous transplant. A myeloablative regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Non-relapse mortality (NRM) at five years was 34% (95% confidence interval (CI) 30-37) and 34% (30-37) for t-MDS and t-AML, respectively. Relapse rates at five years were 46% (43-50) and 43% (40-47), respectively. 5-year OS and DFS was 27% (23-31) and 19% (16-23) for patients with t-MDS and 25% (22-28) and 23% (20-26) for patients with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low risk t-MDS and those receiving MAC HCT during first complete remission (CR1) t-AML, but worse for those with prior autologous HCT, higher risk cytogenetics or IPSS-R score and partially matched unrelated donors (URD). CONCLUSIONS Relapse remains the major cause of treatment failure with little improvement over the past two decades. These data indicate caution in recommending allo-HCT in these conditions. Through better patient optimization, more effective conditioning and studies of post-HCT interventions, outcomes for patients with t-MDS and t-AML may improve

Patterns of oral anticoagulant use and outcomes in Asian patients with atrial fibrillation: a post-hoc analysis from the GLORIA-AF Registry

Background: Previous studies suggested potential ethnic differences in the management and outcomes of atrial fibrillation (AF). We aim to analyse oral anticoagulant (OAC) prescription, discontinuation, and risk of adverse outcomes in Asian patients with AF, using data from a global prospective cohort study. Methods: From the GLORIA-AF Registry Phase II-III (November 2011-December 2014 for Phase II, and January 2014-December 2016 for Phase III), we analysed patients according to their self-reported ethnicity (Asian vs. non-Asian), as well as according to Asian subgroups (Chinese, Japanese, Korean and other Asian). Logistic regression was used to analyse OAC prescription, while the risk of OAC discontinuation and adverse outcomes were analysed through Cox-regression model. Our primary outcome was the composite of all-cause death and major adverse cardiovascular events (MACE). The original studies were registered with ClinicalTrials.gov, NCT01468701, NCT01671007, and NCT01937377. Findings: 34,421 patients were included (70.0 ± 10.5 years, 45.1% females, 6900 (20.0%) Asian: 3829 (55.5%) Chinese, 814 (11.8%) Japanese, 1964 (28.5%) Korean and 293 (4.2%) other Asian). Most of the Asian patients were recruited in Asia (n = 6701, 97.1%), while non-Asian patients were mainly recruited in Europe (n = 15,449, 56.1%) and North America (n = 8378, 30.4%). Compared to non-Asian individuals, prescription of OAC and non-vitamin K antagonist oral anticoagulant (NOAC) was lower in Asian patients (Odds Ratio [OR] and 95% Confidence Intervals (CI): 0.23 [0.22-0.25] and 0.66 [0.61-0.71], respectively), but higher in the Japanese subgroup. Asian ethnicity was also associated with higher risk of OAC discontinuation (Hazard Ratio [HR] and [95% CI]: 1.79 [1.67-1.92]), and lower risk of the primary composite outcome (HR [95% CI]: 0.86 [0.76-0.96]). Among the exploratory secondary outcomes, Asian ethnicity was associated with higher risks of thromboembolism and intracranial haemorrhage, and lower risk of major bleeding. Interpretation: Our results showed that Asian patients with AF showed suboptimal thromboembolic risk management and a specific risk profile of adverse outcomes; these differences may also reflect differences in country-specific factors. Ensuring integrated and appropriate treatment of these patients is crucial to improve their prognosis. Funding: The GLORIA-AF Registry was funded by Boehringer Ingelheim GmbH

Correction to: Comparative effectiveness and safety of non-vitamin K antagonists for atrial fibrillation in clinical practice: GLORIA-AF Registry

International audienceIn this article, the name of the GLORIA-AF investigator Anastasios Kollias was given incorrectly as Athanasios Kollias in the Acknowledgements. The original article has been corrected