SummaryAntibody-blocking studies have demonstrated the role of CD6 in thymocyte-thymic epithelial (TE) cell adhesion. Here we report that CD6 expressed by COS cells mediates adhesion to TE cells and that this interaction is specifically blocked with an anti-CD6 monodonal antibody (mAb) or with a mAb 04-81) that recognized a TE cell antigen. We isolated and expressed a cDNA clone encoding this antigen and show that COS cells transfected with this cDNA bind a CD6 immunoglobulin fusion protein (CD6-Rg). This antigen, which we named ALCAM (activated leukocyte-cell adhesion molecule) because of its expression on activated leukocytes, appears to be the human homologue of the chicken neural adhesion molecule BEN/SC-1/DM-GRASP. The gene was mapped to human chromosome 3q13.1-q13.2 by fluorescence in situ hybridization of cDNA probes to metaphase chromosomes. We prepared an ALCAM-Rg fusion protein and showed that it binds to COS cell transfectants expressing CD6, demonstrating that AI.CAM is a CD6 ligand. The observations that ALCAM is also expressed by activated leukocytes and that both ALCAM and CD6 are expressed in the brain suggest that ALCAM-CD6 interactions may play a role in the binding of T and B cells to activated leukocytes, as well as in interactions between cells of the nervous system.

DOACs were associated with lower or similar risk of major bleeding compared with warfarin in NVAF patients. Apixaban was associated with a significantly lower risk of major bleeding than other DOACs. Dabigatran was associated with a significantly lower risk of major bleeding compared to rivaroxaban and warfarin.

DOACs were associated with similar or lower risks of MB versus warfarin. A lower MB risk was consistently observed for apixaban, but less consistently for dabigatran; MB risk was similar between rivaroxaban and warfarin. Among DOACs, the risk of MB with apixaban was consistently lower than with rivaroxaban, but similar to dabigatran.

Background Stroke is one of the leading causes of cardiovascular-related deaths and disability for adults in Japan and is more commonly seen among the elderly. The risks of developing a secondary stroke resulting in permanent damage after the incident ischemic stroke (IS)/transient ischemic stroke (TIA) are very high. It is critical to understand the treatment landscape for the secondary stroke prevention (SSP) and unmet needs of patients with prior IS/ TIA events. Purpose To evaluate the antiplatelet therapy (APT) treatment patterns for SSP after first hospitalization for IS/TIA events among the Japanese population. Methods Japan's Medical Data Vision (MDV) from Q12011 to Q22021 was used for this study. MDV is a hospital-based claims database covering approximately 35.5 million individuals in the inpatient and outpatient settings among 438 hospitals. Adult patients with an inpatient primary diagnosis of IS/TIA during the index period were identified. Patients require at least one medical claim each quarter within the 1 year before and after index date to ensure longitudinal analysis. Atrial fibrillation patients or patients on oral anticoagulant use were excluded. Patients' characteristics, treatment pattern and duration were evaluated. Results Of 18,948 patients in this study, the mean age was 75 years and 36.7% were female; 91.5% were treated with APT and 8.5% were untreated within 90 days of hospital discharge. Among 17,332 APT treated patients, 76.9% were initiated on single APT (SAPT), 22.7% were initiated on dual APT (DAPT), and <1% were initiated on multiple APT (MAPT). The most used SAPT were aspirin (ASA; 33.2%), clopidogrel (28.7%) or cilostazol (14.8%) and the most used DAPT were ASA+clopidogrel (15.1%), ASA+cilostazol (4.2%) or cilostazol+clopidogrel (2.7%). The median duration of APT was 320, 414 and 411 days for patients who initiated ASA, clopidogrel and cilostazol, respectively. The median duration of APT for patients who initiated ASA+clopidogrel, ASA+cilostazol and cilostazol+clopidogrel was 298, 359 and 473 days respectively. Of patients initiated on ASA+clopidogrel, 52.4% were de-escalated to SAPT (71% clopidogrel, 29% ASA; median duration of 20 days); 36.2% of patients initiated on ASA+cilostazol were de-escalated to SAPT within a median of 19 days (84% cilostazol, 16% ASA); lastly, 54.4% of patients initiated on cilostazol+clopidogrel de-escalated to SAPT within a median of 35 days (76% cilostazol, 24% clopidogrel). Two years after initial hospitalization of IS/TIA, 52%-56% discontinued APT treatments among those previously receiving SAPT while 46%-57% of patients receiving DAPT discontinued treatment. Conclusion Majority of patients at risk of secondary stroke received APT. Further analyses are needed to explore reasons for early APT discontinuation, for no APT use, and to evaluate outcomes of patients in this study. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This study was sponsored by Bristol Myers Squibb and Janssen Research & Development, LLC. – Anonymised and used for statistical purposes only

Background The ARISTOPHANES (Anticoagulants for Reduction In STroke: Observational Pooled analysis on Health outcomes ANd Experience of patientS) study showed that apixaban was associated with lower risks of stroke/systemic embolism (S/SE) and major bleeding (MB) versus dabigatran and rivaroxaban; dabigatran was associated with similar risk of S/SE and lower risk of MB compared to rivaroxaban. Purpose To assess long-term use of non-VKA oral anticoagulants (NOACs) in ARISTOPHANES by evaluating the risk of S/SE and MB among non-valvular atrial fibrillation (NVAF) patients receiving different NOACs by duration of treatment (<1 and ≥1 year). Methods In the ARISTOPHANES study, NVAF patients initiating apixaban, dabigatran, and rivaroxaban from 01/01/2013–09/30/2015 were identified from the CMS Medicare data and four US commercial claims databases, covering >180 million beneficiaries annually (∼56% of US population). After 1:1 propensity score matching (PSM) in each database between NOACs (apixaban-dabigatran, apixaban-dabigatran, and dabigatran-rivaroxaban), the resulting patient records were pooled. Treatment duration was defined as time between the day after the index treatment date and discontinuation (defined using a 30-day gap in the prescription), treatment switch, death, end of study period, or end of continuous medical and pharmacy enrollment, whichever occurred first. Matched patients with observed treatment duration <1 or ≥1 year were separately examined. Cox models were used to estimate hazard ratios of S/SE and MB (identified by inpatient claims) during observed treatment duration. S/SE included ischemic stroke, hemorrhagic stroke, and SE; MB included gastrointestinal (GI) bleeding, intracranial hemorrhage (ICH), and other MB. Results The mean treatment duration for patients with shorter (<1 year) vs longer (≥1 year) duration was ∼4 months vs 18–21 months across the three matched cohorts. All the matched baseline variables remained balanced. The incidence rates of S/SE and MB and the proportion of patients with treatment discontinuation were higher in patients with shorter treatment duration. Regardless of treatment duration, apixaban and dabigatran had a lower risk of MB versus rivaroxaban; and dabigatran had a similar risk of S/SE versus rivaroxaban. Compared to dabigatran patients, apixaban patients with treatment duration <1 year had a lower risk of S/SE and MB, while those with treatment duration ≥1 year had similar S/SE and MB risk. Compared to rivaroxaban patients, apixaban patients with treatment duration <1 year had a lower risk of S/SE, while those with treatment duration ≥1 year had similar S/SE risk. Conclusions Across NVAF patients with duration of treatment <1 and ≥1 year in the ARISTOPHANES study, both apixaban and dabigatran were associated with a lower risk of MB compared to rivaroxaban. These findings indicate varying long-term safety outcomes among different NOACs. Acknowledgement/Funding This study was funded by Bristol-Myers Squibb and Pfizer Inc.

Background The ARISTOPHANES (Anticoagulants for Reduction In STroke: Observational Pooled analysis on Health outcomes ANd Experience of patientS) study showed that non-vitamin K antagonist oral anticoagulants (NOACs) were associated with lower risks of stroke/systemic embolism (S/SE) and variable comparative risks of major bleeding (MB) versus warfarin. Purpose To assess long-term use of non-VKA oral anticoagulants (NOACs) vs. warfarin in ARISTOPHANES by evaluating the risk of S/SE and MB among non-valvular atrial fibrillation (NVAF) patients by duration of treatment (<1 and ≥1 year). Methods In the ARISTOPHANES study, NVAF patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from 01/01/2013–09/30/2015 were identified from the CMS Medicare data and four US commercial claims databases, covering >180 million beneficiaries annually (∼56% of US population). After 1:1 propensity score matching (PSM) in each database between NOACs and warfarin (apixaban-warfarin, dabigatran-warfarin, and rivaroxaban-warfarin), the resulting patient records were pooled. Treatment duration was defined as time between the day after the treatment index date and discontinuation (30 days after a 30-day gap in the prescription), treatment switch, death, end of study period, or end of continuous medical and pharmacy enrollment, whichever occurred first. Matched patients with observed treatment duration <1 or ≥1 year were separately examined. Cox models were used to estimate hazard ratios of S/SE and MB (identified by inpatient claims) during observed treatment duration. Results The mean treatment duration for patients with shorter (<1 year) vs longer (≥1 year) duration was 4–5 months vs 18–21 months across the three matched cohorts. All the matched baseline variables remained balanced. The incidence rates of S/SE and MB and the proportion of patients with treatment discontinuation were higher in patients with shorter treatment duration. Regardless of treatment duration, apixaban patients had a lower risk of S/SE and MB versus warfarin; dabigatran patients had a lower risk of MB versus warfarin; and rivaroxaban patients had a lower risk of S/SE versus warfarin. Compared to warfarin patients, dabigatran patients with treatment duration <1 year had a similar risk of S/SE, while those with treatment duration ≥1 year had lower S/SE risk; rivaroxaban patients with treatment duration <1 year had a higher risk of MB, while those with treatment duration ≥1 year had similar MB risk. Conclusions Among NVAF patients with duration of treatment <1 and ≥1 year in the ARISTOPHANES study, apixaban and rivaroxaban were associated with lower risk of S/SE, while apixaban and dabigatran were associated with lower risk of MB, compared to warfarin. These findings indicate varying long-term effectiveness and safety outcomes between NOACs and warfarin. Acknowledgement/Funding This study was funded by Bristol-Myers Squibb and Pfizer Inc.

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