Incidence and Predictors of Hospitalization in Patients with Atrial Fibrillation: Results from the Chinese Atrial Fibrillation Registry Study

Abstract Background: Patients with atrial fibrillation (AF) underwent a high risk of hospitalization, which, however, has not been paid much attention in clinic. Therefore, we aimed to assess the incidence, causes and predictors of hospitalization in AF patients.Methods: From August 2011 to December 2017, 20,172 AF patients from the Chinese Atrial Fibrillation Registry (China-AF) Study were enrolled in this study. We described the incidence, causes of hospitalization according to age and gender categories. The Cox proportional hazards model was employed to identify predictors of first all-cause and first cause-specific hospitalization. Results: After a mean follow-up of 37.3 ± 20.4 months, 7,512 (37.2%) AF patients experienced one or more hospitalizations. The overall incidence of all-cause hospitalization was 24.0 per 100 patient-years. Patients aged < 65 years were predominantly hospitalized for AF (42.1% of the total frequency of hospitalizations); while patients aged 65-74 and ≥ 75 years were mainly hospitalized for non-cardiovascular diseases (43.6% and 49.3%, respectively). Multivariate Cox model analysis verified the higher risk of hospitalization in patients complicated with heart failure (HF)[hazard ratio (HR) 1.15, 95% confidence interval (CI) 1.08-1.24], established coronary artery disease (CAD) (HR 1.26, 95%CI 1.19-1.34), ischemic stroke/transient ischemic attack (TIA) (HR 1.26, 95%CI 1.18-1.33), diabetes (HR 1.16, 95%CI 1.10-1.22), chronic obstructive pulmonary disease (COPD) (HR 1.41, 95%CI 1.13-1.76), gastrointestinal disorder (HR 1.39, 95%CI 1.23-1.58), and renal dysfunction (HR 1.31, 95%CI 1.16-1.48). Conclusions: More than one-third of AF patients included in this study were hospitalized at least once during almost 3 years of follow-up. The main cause for hospitalization among elderly patients (≥65 years) is non-cardiovascular diseases rather than AF. Multidisciplinary management of comorbidities should be advocated as strategies to reduce hospitalization in AF patients.Clinical Trial Registration: URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.

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Incidence and predictors of hospitalization in patients with atrial fibrillation: results from the Chinese atrial fibrillation registry study

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01951-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zhaojie Dong ◽

Xin Du ◽

Shangxin Lu ◽

Chao Jiang ◽

Shijun Xia ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cardiovascular Diseases ◽

Risk Model ◽

Age Groups ◽

Gastrointestinal Disorder ◽

The Elderly ◽

Chronic Obstructive ◽

Unique Identifier ◽

Clinical Registry

Abstract Background Patients with atrial fibrillation (AF) underwent a high risk of hospitalization, which has not been paid much attention to in practice. Therefore, we aimed to assess the incidence, causes and predictors of hospitalization in AF patients. Methods From August 2011 to December 2017, a total number of 20,172 AF patients from the Chinese Atrial Fibrillation Registry (China-AF) Study were prospectively selected for this study. We described the incidence, causes of hospitalization by age groups and sex. The Fine-Gray competing risk model was employed to identify predictors of first all-cause and first cause-specific hospitalization. Results After a mean follow-up of 37.3 ± 20.4 months, 7,512 (37.2%) AF patients experienced one or more hospitalizations. The overall incidence of all-cause hospitalization was 24.0 per 100 patient-years. Patients aged < 65 years were predominantly hospitalized for AF (42.1% of the total hospitalizations); while patients aged 65–74 and ≥ 75 years were mainly hospitalized for non-cardiovascular diseases (43.6% and 49.3%, respectively). We found patients complicated with heart failure (HF)[hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.02–1.18], established coronary artery disease (CAD) (HR 1.24, 95%CI 1.17–1.33), ischemic stroke/transient ischemic attack (TIA) (HR 1.22, 95%CI 1.15–1.30), diabetes (HR 1.14, 95%CI 1.08–1.20), chronic obstructive pulmonary disease (COPD) (HR 1.28, 95%CI 1.02–1.62), gastrointestinal disorder (HR 1.37, 95%CI 1.21–1.55), and renal dysfunction (HR 1.24, 95%CI 1.09–1.42) had higher risks of hospitalization. Conclusions More than one-third of AF patients included in this study were hospitalized at least once during over 3-year follow-up. The main cause for hospitalization among the elderly patients (≥ 65 years) is non-cardiovascular diseases rather than AF. Multidisciplinary management of comorbidities should be advocated to reduce hospitalization in AF patients older than 65 years old. Clinical Registryhttp://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729. The registration date is October 22, 2013.

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Dynamic changes of cardiovascular biomarkers after ablation for atrial fibrillation: observations from AXAFA-AFNET5

European Heart Journal ◽

10.1093/eurheartj/ehab724.0538 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

W Chua ◽

L Di Biase ◽

A Bayes De Luna ◽

C David ◽

D Haase ◽

...

Keyword(s):

Atrial Fibrillation ◽

Proportional Hazards Model ◽

Cox Proportional Hazards Model ◽

Chronic Obstructive ◽

Dynamic Changes ◽

Cardiovascular Research ◽

Increased Risk ◽

Males And Females ◽

Cardiovascular Biomarkers

Abstract Background The dynamic changes and stability of blood biomarkers over time and after treatment are not well known. In this study, we describe changes in 12 centrally quantified known and novel cardiovascular biomarkers, prior to and 3 months after ablation for atrial fibrillation (AF). Purpose In patients enrolled in the AXAFA-AFNET5 trial, we 1) characterised changes in 12 biomarker levels pre and post-ablation, 2) ascertained if biomarker changes are consistent between males and females, and 3) identified biomarkers which predict recurrent AF post-ablation. Methods and results Of the 674 patients who were recruited and randomised, 633 received the study drug and underwent ablation. Peripheral blood samples were available for 488 patients at baseline and 434 at 3 months follow-up (median age [Q1, Q3] 64 [58, 70] years; 34% female). Between baseline (BL) and follow-up (FU), paired comparisons revealed that 3 biomarkers decreased, ANG2 (median [Q1, Q3] BL 2.185 [1.711, 3.115], FU 1.827 [1.457, 2.297] ng/mL, p<0.001), BMP10 (BL 2.056 [1.810, 2.380], FU 1.986 [1.757, 2.260] ng/mL, p<0.001), and NTproBNP (BL 2.219 [0.858, 5.731] per 100pg/mL, p<0.001), while 1 biomarker increased, FABP3 (BL 2.911 [2.425, 3.508], FU 2.911 [2.462, 3.521], p=0.005). The remaining 8 biomarkers remained unchanged. Significant differences in ANG2, BMP10, NTproBNP and FABP3 were driven by patients who remained arrhythmia free at follow-up whereas biomarker levels remained unchanged in 121 patients who experienced recurrent AF (39%; Figure). Change scores were mainly consistent between males and females, however, CRP decreased significantly more in females. Recurrent AF episodes were not different between males and females (p=0.319). Cox proportional hazards model assessed the relationship of individual biomarkers at baseline for predicting recurrent AF. Elevated ANG2 (hazard ratio, HR per ng/mL [95% confidence interval] 1.214 [1.113, 1.325]), BMP10 (HR per ng/mL 1.516 [1.039, 2.214]), and NTproBNP (HR per 100 pg/mL 1.050 [1.025, 1.076]) significantly predicted increased risk for recurrent AF, after adjustment for age, sex, body mass index, hypertension, diabetes, chronic obstructive pulmonary disease, stroke, heart failure, ablation type (PVI, PVI and other, other), ablation energy (radiofrequency, cryoablation, other), and treatment arm. Conclusion In this study, most cardiovascular biomarkers are unchanged after ablation for AF, however, ANG2, BMP10, and NTproBNP decreased at follow-up. These effects are driven by patients who remained arrhythmia free and could potentially reflect improvement in vascular (ANG2), endothelial (BMP10), and myocardial load (NTproBNP) parameters post-ablation. This outcome corresponds with the observation that elevated levels of these biomarkers at baseline predict recurrent AF at 3 months. Both males and females demonstrate similar changes in biomarker profiles and benefit equally from ablation for AF. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): DZHK (German Centre for Cardiovascular Research) and BMBF (German Ministry of Education and Research) to AFNET.Additional support from European Union [grant agreement No. 633196 (CATCH ME)]. Biomarker changes

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P6355The behavior of atrial fibrillation in patients with heart failure hospitalization

European Heart Journal ◽

10.1093/eurheartj/ehz746.0951 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M Fukunaga ◽

K Hirose ◽

A Isotani ◽

T Morinaga ◽

K Ando

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Cardiovascular Disease ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Significant Difference ◽

The Impact

Abstract Background Relationship between atrial fibrillation (AF) and heart failure (HF) is often compared with proverbial question of which came first, the chicken or the egg. Some patients showing AF at the HF admission result in restoration of sinus rhythm (SR) at discharge. It is not well elucidated that the restoration into SR during hospitalization can render the preventive effect for rehospitalization. Purpose To investigate the impact of restoration into SR during hospitalization for readmission rate of the HF patients showing AF. Methods We enrolled consecutive 640 HF patients hospitalized from January 2015 to December 2015. Patients data were retrospectively investigated from medical record. Patients showing atrial fibrillation on admission but unrecognized ever were defined as “incident AF”; patients with AF diagnosed before admission were defined as “prevalent AF”. Primary endpoint was a composite of death from cardiovascular disease or hospitalization for worsening heart failure. Secondary endpoints were death from cardiovascular disease, unplanned hospitalization related to heart failure, and any hospitalization. Results During mean follow up of 19 months, 139 patients (22%) were categorized as incident AF and 145 patients (23%) were categorized as prevalent AF. Among 239 patients showing AF on admission, 44 patients were discharged in SR (39 patients in incident AF and 5 patients in prevalent AF). Among incident AF patients, the primary composite end point occurred in significantly fewer in those who discharged in SR (19% vs. 42% at 1-year; 23% vs. 53% at 2-year follow-up, p=0.005). To compare the risk factors related to readmission due to HF with the cox proportional-hazards model, AF only during hospitalization [Hazard Ratio (HR)=0.37, p<0.01] and prevalent AF (HR=1.67, p=0.04) was significantly associated. There was no significant difference depending on LVEF. Conclusion Newly diagnosed AF with restoration to SR during hospitalization was a good marker to forecast future prognosis.

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Nonlinear relationship between serum total bilirubin levels and initial ischemic stroke in patients with non-valvular atrial fibrillation

Journal of International Medical Research ◽

10.1177/0300060520962347 ◽

2020 ◽

Vol 48 (10) ◽

pp. 030006052096234

Author(s):

Ying Liu ◽

Jie Wang ◽

Wen-zhen Zeng ◽

Qing-shan Lyu

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Proportional Hazards ◽

Total Bilirubin ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Serum Total Bilirubin ◽

Hazards Model

Objective This study aimed to examine the relationship between total bilirubin levels and initial ischemic stroke in patients with non-valvular atrial fibrillation. Methods This was a retrospective study. Atrial fibrillation was diagnosed by 24-hour Holter electrocardiography and serum total bilirubin levels were divided into quintiles. Ischemic stroke was diagnosed by symptoms, signs, and a medical image examination. The multivariate Cox proportional hazards model and survival analysis were used to estimate the association of total bilirubin with initial ischemic stroke. Results We studied 316 patients with non-valvular atrial fibrillation. During follow-up, there were 42 (13.29%) first ischemic strokes. After multivariate adjustment, for each 1 µmol/L increase in total bilirubin, the risk of first ischemic stroke increased by 4% (95% confidence interval [CI]: 1.01, 1.07). When using the first quintile as the reference, from the second to fifth quintiles, the risks of first ischemic stroke were 0.52 (95% CI: 0.17, 1.65), 0.23 (95% CI: 0.06, 0.87), 0.92 (95% CI: 0.32, 2.67), and 1.33 (95% CI: 1.09, 4.41), respectively. The optimal cut-off point of total bilirubin for the lowest risk of ischemic stroke was 17.0 µmol/L. Conclusions Total bilirubin levels are nonlinearly associated with initial ischemic stroke in patients with non-valvular atrial fibrillation.

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Abstract 339: Hospitalization Rates and Healthcare Costs Among Non-valvular Atrial Fibrillation Patients Who Were Naïve Users of Novel Oral Anticoagulants

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.8.suppl_2.339 ◽

2015 ◽

Vol 8 (suppl_2) ◽

Author(s):

Steve Deitelzweig ◽

Amanda Bruno ◽

Natalie Tate ◽

Augustina Ogbonnaya ◽

Manan Shah ◽

...

Keyword(s):

Atrial Fibrillation ◽

Real World ◽

Index Date ◽

Proportional Hazards Model ◽

Oral Anticoagulants ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Novel Oral Anticoagulants ◽

Early Assessment

Background: Novel oral anticoagulants (NOACs) are recommended for stroke risk reduction in non-valvular atrial fibrillation (NVAF) patients withCHADS 2 ≥2. Efficacy and safety of the different NOACs are well documented in the clinical trial setting, however, real-world evidence of the effectiveness and safety of these agents is limited. This study provides an early assessment of all-cause hospitalizations and economic outcomes among NVAF patients initiated on different NOAC treatments in the real-world. Methods: A retrospective cohort study of patients diagnosed with AF (ICD-9-CM 427.31 and 427.32) who were naïve to anticoagulant therapy and initiated on a NOAC (dabigatran, rivaroxaban and apixaban) was conducted using PharMetrics Plus data from 01/ 2012 through 03/2014. The first NOAC prescription date served as the index date. Patients were required to be ≥18 years old and have no evidence of valvular disease, CHADS 2 score ≥ 1, and ≥ 1 month of follow-up. Follow-up ended upon the earliest of the following: treatment discontinuation, switch to a different NOAC, end of continuous enrollment, 1 year after the index date, or end of study. A Cox proportional hazards model were used to model the likelihood and timing of all-cause hospitalizations while a generalized linear model (GLM) was used for costs. Results: There were 9,150 patients included in the study. The majority of patients were prescribed rivaroxaban (61.5%), followed by dabigatran 1,374 (23.5%), and apixaban (15.0%). Males were 71.4% of the sample and mean age was 63.4 years, with the apixaban patients being slightly older (P=0.0170). Mean CHADS 2 score was 1.8. Mean HAS-BLED score was 2.0, and was slightly higher for patients on apixaban and rivaroxaban (P=0.0025). After adjusting for baseline characteristics, treatment with dabigatran (HR 1.37, 95% CI 1.10-1.69) and rivaroxaban (HR 1.57, 95% CI 1.30-1.90) was associated with increased rate of all-cause hospitalization relative to apixaban. Mean monthly all-cause costs were lower for patients on apixaban compared to those on dabigatran ($3,581 vs $4,236; P<0.0001) and rivaroxaban ($3,581 vs $4,144; P<0.0001). Conclusions: This early assessment shows that among anticoagulant naïve NVAF patients, treatment with apixaban was associated with a lower rate of all-cause hospitalization, as well as lower overall costs compared to other NOACs. Further evaluation is needed to provide additional detail on potential drivers of utilization differences.

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Risk factors associated with major adverse cardiac and cerebrovascular events following percutaneous coronary intervention: a 10-year follow-up comparing random survival forest and Cox proportional-hazards model

BMC Cardiovascular Disorders ◽

10.1186/s12872-020-01834-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Maryam Farhadian ◽

Sahar Dehdar Karsidani ◽

Azadeh Mozayanimonfared ◽

Hossein Mahjub

Keyword(s):

Proportional Hazards ◽

Proportional Hazards Model ◽

Coronary Intervention ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Cerebrovascular Events ◽

Long Term Follow Up ◽

Stent Length

Abstract Background Due to the limited number of studies with long term follow-up of patients undergoing Percutaneous Coronary Intervention (PCI), we investigated the occurrence of Major Adverse Cardiac and Cerebrovascular Events (MACCE) during 10 years of follow-up after coronary angioplasty using Random Survival Forest (RSF) and Cox proportional hazards models. Methods The current retrospective cohort study was performed on 220 patients (69 women and 151 men) undergoing coronary angioplasty from March 2009 to March 2012 in Farchshian Medical Center in Hamadan city, Iran. Survival time (month) as the response variable was considered from the date of angioplasty to the main endpoint or the end of the follow-up period (September 2019). To identify the factors influencing the occurrence of MACCE, the performance of Cox and RSF models were investigated in terms of C index, Integrated Brier Score (IBS) and prediction error criteria. Results Ninety-six patients (43.7%) experienced MACCE by the end of the follow-up period, and the median survival time was estimated to be 98 months. Survival decreased from 99% during the first year to 39% at 10 years' follow-up. By applying the Cox model, the predictors were identified as follows: age (HR = 1.03, 95% CI 1.01–1.05), diabetes (HR = 2.17, 95% CI 1.29–3.66), smoking (HR = 2.41, 95% CI 1.46–3.98), and stent length (HR = 1.74, 95% CI 1.11–2.75). The predictive performance was slightly better by the RSF model (IBS of 0.124 vs. 0.135, C index of 0.648 vs. 0.626 and out-of-bag error rate of 0.352 vs. 0.374 for RSF). In addition to age, diabetes, smoking, and stent length, RSF also included coronary artery disease (acute or chronic) and hyperlipidemia as the most important variables. Conclusion Machine-learning prediction models such as RSF showed better performance than the Cox proportional hazards model for the prediction of MACCE during long-term follow-up after PCI.

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Elevated plasma growth and differentiation factor 15 predicts incident anemia in older adults aged 60 years and older

The Journals of Gerontology Series A ◽

10.1093/gerona/glaa324 ◽

2020 ◽

Author(s):

Yuko Yamaguchi ◽

Marta Zampino ◽

Toshiko Tanaka ◽

Stefania Bandinelli ◽

Yusuke Osawa ◽

...

Keyword(s):

Older Adults ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Differentiation Factor ◽

Hazards Model ◽

Increased Risk ◽

The Relationship

Abstract Background Anemia is common in older adults and associated with greater morbidity and mortality. The causes of anemia in older adults have not been completely characterized. Although elevated circulating growth and differentiation factor 15 (GDF-15) has been associated with anemia in older adults, it is not known whether elevated GDF-15 predicts the development of anemia. Methods We examined the relationship between plasma GDF-15 concentrations at baseline in 708 non-anemic adults, aged 60 years and older, with incident anemia during 15 years of follow-up among participants in the Invecchiare in Chianti (InCHIANTI) Study. Results During follow-up, 179 (25.3%) participants developed anemia. The proportion of participants who developed anemia from the lowest to highest quartile of plasma GDF-15 was 12.9%, 20.1%, 21.2%, and 45.8%, respectively. Adults in the highest quartile of plasma GDF-15 had an increased risk of developing anemia (Hazards Ratio 1.15, 95% Confidence Interval 1.09, 1.21, P<.0001) compared to those in the lower three quartiles in a multivariable Cox proportional hazards model adjusting for age, sex, serum iron, soluble transferrin receptor, ferritin, vitamin B12, congestive heart failure, diabetes mellitus, and cancer. Conclusions Circulating GDF-15 is an independent predictor for the development of anemia in older adults.

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Clinical impact of regression from sustained to paroxysmal atrial fibrillation: the Fushimi AF registry

European Heart Journal ◽

10.1093/ehjci/ehaa946.0678 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Fujino ◽

H Ogawa ◽

S Ikeda ◽

K Doi ◽

Y Hamatani ◽

...

Keyword(s):

Cardiac Death ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Clinical Impact ◽

Cox Proportional Hazards Model ◽

Cardiac Events ◽

Hazards Model ◽

Adverse Cardiac Events

Abstract Background Atrial fibrillation (AF) commonly progresses from paroxysmal type to sustained type in the natural course of the disease, and we previously demonstrated that the progression of AF was associated with increased risk of clinical adverse events. There are some patients, though less frequently, who regress from sustained to paroxysmal AF, but the clinical impact of the regression of AF remains unknown. Purpose We sought to investigate whether regression from sustained to paroxysmal AF is associated with better clinical outcomes. Methods Using the dataset of the Fushimi AF Registry, patients who were diagnosed as sustained (persistent or permanent) AF at baseline were studied. Conversion of sustained AF to paroxysmal AF during follow-up was defined as regression of AF. Major adverse cardiac events (MACE) were defined as the composite of cardiac death, stroke, and hospitalization for heart failure (HF). Event rates were compared between the patients with and without regression of AF. In patients with sustained AF at baseline, predictors of MACE were identified using Cox proportional hazards model. Results Among 2,253 patients who were diagnosed as sustained AF at baseline, regression of AF was observed in 9.0% (202/2,253, 2.0 per 100 patient-years) during a median follow-up of 4.0 years. Of these, 24.3% (49/202, 4.6 per 100 patient-years) of the patients finally recurred to sustained AF during follow-up. The proportion of asymptomatic patients was lower in patients with regression of AF than those without (with vs without regression; 49.0% vs 69.5%, p<0.01). The percentage of beta-blocker use at baseline was similar between the two groups (37.2% vs 33.8%, p=0.34). The prevalence of patients who underwent catheter ablation or electrical cardioversion during follow-up was higher in patients with regression of AF (catheter ablation: 15.8% vs 5.5%; p<0.01, cardioversion: 4.0% vs 1.4%; p<0.01, respectively). The rate of MACE was significantly lower in patients with regression of AF as compared with patients who maintained sustained AF (3.7 vs 6.2 per 100 patient-years, log-rank p<0.01). Figure shows the Kaplan-Meier curves for MACE, cardiac death, hospitalization for heart failure, and stroke. In patients with sustained AF at baseline, multivariable Cox proportional hazards model demonstrated that regression of AF was an independent predictor of lower MACE (adjusted hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.28 to 0.88, p=0.02), stroke (HR: 0.51, 95% CI: 0.30 to 0.88, p=0.02), and hospitalization for HF (HR: 0.50, 95% CI: 0.29 to 0.85, p=0.01). Conclusion Regression from sustained to paroxysmal AF was associated with a lower incidence of adverse cardiac events. Funding Acknowledgement Type of funding source: None

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CTIM-10. REPRODUCIBILITY OF CLINICAL TRIALS USING CMV-TARGETED DENDRITIC CELL VACCINES IN PATIENTS WITH GLIOBLASTOMA

Neuro-Oncology ◽

10.1093/neuonc/noab196.202 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi51-vi51

Author(s):

Kristen Batich ◽

Duane Mitchell ◽

Patrick Healy ◽

James Herndon ◽

Gloria Broadwater ◽

...

Keyword(s):

Clinical Trials ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Recurrent Glioblastoma ◽

Cox Proportional Hazards Model ◽

Total N ◽

Dc Vaccine ◽

Dc Vaccines

Abstract INTRODUCTION Vaccination with dendritic cells (DCs) fares poorly in primary and recurrent glioblastoma (GBM). Moreover, GBM vaccine trials are often underpowered due to limited sample size. METHODS To address these limitations, we conducted three sequential clinical trials utilizing Cytomegalovirus (CMV)-specific DC vaccines in patients with primary GBM. Autologous DCs were generated and electroporated with mRNA encoding for the CMV protein pp65. Serial vaccination was given throughout adjuvant temozolomide cycles, and 111Indium radiolabeling was implemented to assess migration efficiency of DC vaccines. Patients were followed for median overall survival (mOS) and OS. RESULTS Our initial study was the phase II ATTAC study (NCT00639639; total n=12) with 6 patients randomized to vaccine site preconditioning with tetanus-diphtheria (Td) toxoid. This led to an expanded cohort trial (ATTAC-GM; NCT00639639) of 11 patients receiving CMV DC vaccines containing granulocyte-macrophage colony-stimulating factor (GM-CSF). Follow-up data from ATTAC and ATTAC-GM revealed 5-year OS rates of 33.3% (mOS 38.3 months; CI95 17.5-undefined) and 36.4% (mOS 37.7 months; CI95 18.2-109.1), respectively. ATTAC additionally revealed a significant increase in DC migration to draining lymph nodes following Td preconditioning (P=0.049). Increased DC migration was associated with OS (Cox proportional hazards model, HR=0.820, P=0.023). Td-mediated increased migration has been recapitulated in our larger confirmatory trial ELEVATE (NCT02366728) of 43 patients randomized to preconditioning (Wilcoxon rank sum, Td n=24, unpulsed DC n=19; 24h, P=0.031 and 48h, P=0.0195). In ELEVATE, median follow-up of 42.2 months revealed significantly longer OS in patients randomized to Td (P=0.026). The 3-year OS for Td-treated patients in ELEVATE was 34% (CI95 19-63%) compared to 6% given unpulsed DCs (CI95 1-42%). CONCLUSION We report reproducibility of our findings across three sequential clinical trials using CMV pp65 DCs. Despite their small numbers, these successive trials demonstrate consistent survival outcomes, thus supporting the efficacy of CMV DC vaccine therapy in GBM.

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Abstract 15567: Residual Cholesterol and Cardiovascular Events in Patients With Coronary Artery Disease Under Different Glucose Metabolism Status

Circulation ◽

10.1161/circ.142.suppl_3.15567 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Jian-jun Li ◽

Yexuan Cao ◽

Hui-Wen Zhang ◽

Jing-Lu Jin ◽

Yan Zhang ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Glucose Metabolism ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Significant Difference ◽

Artery Disease

Introduction: The atherogenicity of residual cholesterol (RC) has been underlined by recent guidelines, which was linked to coronary artery disease (CAD), especially for patients with diabetes mellitus (DM). Hypothesis: This study aimed to examine the prognostic value of plasma RC, clinically presented as triglyceride-rich lipoprotein-cholesterol (TRL-C) or remnant-like lipoprotein particles-cholesterol (RLP-C), in CAD patients with different glucose metabolism status. Methods: Fasting plasma TRL-C and RLP-C levels were directly calculated or measured in 4331 patients with CAD. Patients were followed for incident MACEs for up to 8.6 years and categorized according to both glucose metabolism status [DM, pre-DM, normal glycaemia regulation (NGR)] and RC levels. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence intervals. Results: During a mean follow-up of 5.1 years, 541 (12.5%) MACEs occurred. The risk for MACEs was significantly higher in patients with elevated RC levels after adjustment for potential confounders. No significant difference in MACEs was observed between pre-DM and NGR groups (p>0.05). When stratified by status of glucose metabolism and RC levels, highest levels of RLP-C, calculated and measured TRL-C were significant and independent predictors of developing MACEs in pre-DM (HR: 2.10, 1.98, 1.92, respectively; all p<0.05) and DM (HR: 2.25, 2.00, 2.16, respectively; all p<0.05). Conclusions: In this large cohort study with long-term follow-up, data firstly demonstrated that higher RC levels were significantly associated with the worse prognosis in DM and pre-DM patients with CAD, suggesting RC might be a target for patients with impaired glucose metabolism.

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