Statin Use Was Associated With a Non-Significant Reduction In The Observed Incidence Of Recurrent VTE In Einstein-DVT and Einstein-PE

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1135-1135
Author(s):  
Martin Gebel ◽  
Martin Prins ◽  
Anthonie WA Lensing
Keyword(s):  
Major Bleeding ◽  
Research Funding ◽  
Randomized Clinical Trials ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Bleeding Events ◽  
Recurrent Vte ◽  
Statin Use

Abstract Background Several observational studies in patients at high risk of arterial vascular disease have shown that statin use is associated with a decreased risk of venous thromboembolism (VTE). A recent meta-analysis showed that the odds ratio for a first venous thromboembolic event for statin users was 0.89 (95% confidence interval [CI], 0.78–1.01) compared with non-users (Rahmini K, et al. PLoS Med 2012;9: e1001310 doi:10.1371/journal.pmed.1001310). Objective To evaluate the risk of recurrent VTE in patients with VTE treated with an anticoagulant (rivaroxaban or enoxaparin/vitamin K antagonist [VKA]) in relation to the concomitant use of statin therapy in the EINSTEIN-DVT and EINSTEIN-PE studies. Measurements Incidence densities of symptomatic recurrent VTE and major bleeding were expressed per 100 patient-years of exposure (or not) to statins. A Cox proportional hazards model was employed, with statin use as a time-dependent variable, for each treatment group (rivaroxaban vs enoxaparin/VKA) and adjusted for aspirin use, age, body mass index, cardiac disorders, gender, and creatinine clearance at baseline. Results A total of 1509 (18%) of the 8240 patients included in EINSTEIN-DVT and EINSTEIN-PE used statins during the course of the studies. Statin users were more likely to have cardiovascular disorders (31% vs 10%) and also used aspirin more often (26% vs 5%). During statin/rivaroxaban treatment, recurrent VTE occurred with an incidence of 2.0 per 100 patient-years versus 3.6 during non-statin-use (adjusted hazard ratio [HR], 0.62; 95% CI, 0.29–1.32). During statin/enoxaparin/VKA use, recurrent VTE occurred at an incidence of 3.2 per 100 patient-years versus 4.0 during non-statin-use (adjusted HR, 0.89; 95% CI, 0.47–1.69). Major bleeding during statin/rivaroxaban treatment occurred at an incidence of 2.2 per 100 patient-years versus 1.6 during non-statin-use (adjusted HR, 0.92; 95% CI, 0.43–1.98). During statin/enoxaparin/VKA treatment, the rate of major bleeding was 3.7 per 100 patient-years compared with 3.0 during non-statin-use (adjusted HR, 0.69; 95% CI, 0.36–1.32). Due to the adjustments in the Cox regression model the direction of these hazard ratios are in contrast to the crude comparison of rates by patient-years. This is largely because, in general, statin users are older and most of the major bleeding events in statin users occur in the ≥60 years age group. Limitations The study comprised a post-hoc analysis of data collected in two randomized clinical trials. Because the analyses were not a comparison of randomized groups, residual confounding is possible. Conclusions A modest, but not statistically significant, reduction in recurrent VTE was observed with statin use in patients treated for VTE. This reduction was similar in patients receiving enoxaparin/VKA or rivaroxaban therapy. Disclosures: Gebel: Bayer HealthCare AG: Employment, Equity Ownership. Prins:Bayer HealthCare: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding; sanofi-aventis: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; LeoPharma: Consultancy, Honoraria, Research Funding; ThromboGenics: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Lensing:Bayer HealthCare: Employment.

Treatment of venous thromboembolism with rivaroxaban in relation to body weight

2016 ◽  
Vol 116 (10) ◽  
pp. 739-746 ◽  
Author(s):  
Maria C. Vedovati ◽  
Antoni Riera-Mestre ◽  
Martin H. Prins ◽  
Katharina Mueller ◽  
Alexander T. Cohen ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Treatment Period ◽  
Major Bleeding ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards Model ◽  
Fixed Dose ◽  
Bleeding Events ◽  
Hazard Ratios ◽  
Increased Risk ◽  
Recurrent Vte

SummaryThe pharmacokinetics of oral rivaroxaban are highly predictable and only affected to a limited extent by bodyweight; therefore, dose adjustments for bodyweight are not required. However, this raises concerns among physicians for potential under- or overdosing. This substudy of the randomised EINSTEIN DVT and EINSTEIN PE trials, which compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy, aimed to determine the incidence of major bleeding in patients with a low bodyweight and recurrent venous thromboembolism (VTE) in patients with a high bodyweight during rivaroxaban or enoxaparin/VKA therapy. More than 8,000 patients with objectively diagnosed deepvein thrombosis or pulmonary embolism were included. Adjusted hazard ratios for recurrent VTE and bleeding were calculated using the Cox proportional hazards model. Analyses were performed for both the first 21 days of treatment and the whole treatment period. For rivaroxaban recipients, there was no association between bodyweight or body mass index (BMI) and risk of recurrent VTE (ptrend=0.87 and 0.62, respectively), major bleeding (ptrend=0.24 and 0.36, respectively) or clinically relevant bleeding (ptrend=0.17 and 0.63, respectively). Major bleeding events were numerically lower in rivaroxaban patients across all bodyweight and BMI categories. Hazard ratios for rivaroxaban vs enoxaparin/VKA were similar in all bodyweight and BMI categories, both during the first 21 days and the whole treatment period. The fixed-dose rivaroxaban regimen is not associated with an increased risk of major bleeding or recurrent VTE in patients with either a low or high bodyweight. A high BMI was not associated with an increased risk of recurrent VTE during anticoagulation.Note: This study was presented at the 25th Congress of the International Society on Thrombosis and Haemostasis; June, 2015, Toronto, Canada. Trial registration: EINSTEIN DVT (NCT00440193), EINSTEIN PE (NCT00439777).

Abstract 17617: History of Bleeding and Outcomes with Apixaban versus Warfarin in Patients with Atrial Fibrillation in the ARISTOTLE Trial

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Raffaele De Caterina ◽  
Ulrika Andersson ◽  
John H Alexander ◽  
M.Cecilia Bahit ◽  
Patrick J Commerford ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Weight ◽  
Major Bleeding ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Channel Blockers ◽  
Chads2 Score ◽  
History Of

Background: History of bleeding is important in decisions for anticoagulation. We analyzed outcomes in relation to history of bleeding and randomized treatments in patients with atrial fibrillation (AF) in the ARISTOTLE trial. Methods: The on-treatment safety population included 18,140 patients receiving ≥1 dose of study drug, apixaban 5 mg bd (2.5 mg bd if 2 of the following: age >80 yrs; body weight <60 kg; or creatinine >133 μmol/L) or warfarin aiming for INR 2.0-3.0 (median TTR 66%), for a median of 1.8 yrs. Adjudicated outcomes in relation to randomization and history of bleeding were analyzed using a Cox proportional hazards model. Efficacy endpoints were analyzed in the intention-to-treat population. Results: A history of bleeding was reported in 3033 patients (16.7%), who more often were male (68% vs 64%, p <0.0005); with a history of prior stroke/TIA/systemic embolism (23% vs 19%, p <0.0001); diabetes (27% vs 24%, p=0.0010); higher CHADS2 score (CHADS2 >3: 35% vs 29%), age (mean [SD] 71 [9] vs 69 [10], p <0001) and body weight (86 [21] vs 84 [21], p <0.0001); lower creatinine clearance (77 [33] vs 80 [33], p=0.0007) and mean systolic blood pressure (131 [17] vs 132 [16], p=0.0027). Calcium channel blockers, statins, non-steroidal anti-inflammatory drugs and proton pump inhibitors were used more often in patients with vs without a history of bleeding. Major bleeding was the only outcome event occurring more frequently in patients with vs without a history of bleeding, HR 1.7 (95% CI 1.4-2.3) with apixaban and 1.5 (1.2-1.0) with warfarin. Primary efficacy and safety outcomes in relation to randomization, see Table. Conclusions: In patients with AF, a history of bleeding was associated with several risk factors for stroke and bleeding and, accordingly, a higher bleeding risk during anticoagulation. Benefits with apixaban vs warfarin as to stroke, mortality and major bleeding, are however consistent irrespective of bleeding history.

scholarly journals Trajectories of Mediterranean Diet Adherence and Risk of Hypertension in China: Results from the CHNS Study, 1997–2011

Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 2014 ◽  
Author(s):  
Min Gao ◽  
Fengbin Wang ◽  
Ying Shen ◽  
Xiaorou Zhu ◽  
Xing Zhang ◽  
...  
Keyword(s):  
Mediterranean Diet ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Nutrition Survey ◽  
Cox Regression Analysis ◽  
Incident Hypertension ◽  
Diet Adherence ◽  
Mediterranean Diet Adherence

Evidence indicates that longitudinal changes in dietary patterns may predict variations in blood pressure (BP) and risk of incident hypertension. We aimed to identify distinct trajectories in the levels of Mediterranean diet adherence (MDA) in China and explore their association with BP levels and hypertension risk using the China Health and Nutrition Survey 1997–2011 data. Three levels of MDA were constructed. The trajectories in these levels were constructed using group-based trajectory modeling. A Cox proportional hazards model was used to measure the association between MDA trajectory groups and the risk of incident hypertension after adjusting for covariates. Finally, 6586 individuals were included. Six distinct MDA trajectory groups were identified: persistently low and gradual decline; rapidly increasing and stabilized; persistently moderate; slightly increasing, steady, and acutely descending; slightly decreasing and acutely elevated; and persistently high. The systolic BP and diastolic BP were significantly lower in trajectory groups with rapidly increasing and stabilized MDA; slightly increasing, steady, and acutely descending MDA; and persistently high MDA. Cox regression analysis showed that the risks of developing hypertension were relatively lower in the group with slightly increasing, steady, and acutely descending MDA (hazard ratio (HR) = 0.17, 95% confidence interval (CI): 0.09–0.32) and the group with rapidly increasing and stabilized MDA (HR = 0.32, 95% CI: 0.23–0.42), but the risk was the highest in the trajectory with persistently moderate MDA (HR = 0.96, 95% CI: 0.84–1.08). In conclusion, MDA in China was categorized into six distinct trajectory groups. BP was relatively lower in trajectory groups with initially high or increasing MDA levels. Greater MDA was significantly associated with a lower risk of developing hypertension.

scholarly journals Narrowing of the Racial Disparities Gap in Survival of Patients with Mycosis Fungoides: A Longitudinal Analysis of the SEER Database (1988 to 2011)

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1392-1392
Author(s):  
Noha Soror ◽  
Hamid D. Ismail ◽  
Catherine Chung ◽  
Basem M. William
Keyword(s):  
Racial Disparities ◽  
Research Funding ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
P Value ◽  
Time Period ◽  
Black Patients ◽  
Over Time

Abstract I ntroduction: Mycosis Fungoides (MF) is the most common subtype of cutaneous T-cell lymphomas. Prior Studies have identified Black race as a risk factor for earlier age at diagnosis, more advanced stages at time of diagnosis and poor prognosis in patients with MF. Data examining differences in racial disparities outcomes over time are limited. Objective: This retrospective analysis aims to examine if the racial disparities in survival outcomes of MF patients have improved over time. Subjects and Methods: Using the United States Surveillance, Epidemiology and End Results (SEER) 1988-2011 public use database, we examined survival patterns for patients with MF (with the code of 9700) between 1988 and 2011. Cases were divided into three cohorts based on the year of diagnosis; "1988 - 1995", "1996 - 2003", and "2004 - 2011". Univariable and multivariable analysis were conducted to assess for factors significantly associated with the overall survival. The nonparametric estimates of the survival distribution function, Kaplan and Meier survival curves, and Cox proportional hazards model were used to investigate the factors affecting the survival time. Results: From 1988 to 2011, a total of 2896 cases of MF were identified with a median follow-up of 60 months. The difference in the survival time between the years of diagnosis 1988-1995 and 2004-2011 is significant (p-value=0.05). The parameter estimate of the Cox proportional hazards model for the "1988-1995" and the "2004-2011" period as a reference is also significant (p-value = 0.024) and the hazard ratio (HR) is 1.407, which means that patients diagnosed in 1988-1995 were 1.4 times likely to die from the disease compared to the patients diagnosed in 2004-2011 (i.e. patients in 1988-1995 were more likely to not survive than in 2004-2011) (Table 1 and 2). There is no significant difference in the survival of the patients between "1996-2003" and "2004-2011" (p-value 0.998), Cox model estimate is not significant (p-value = 0.178), and the HR is 0.94 (Table 1 and 2). For the time period 1988-1995, the survival of Black patients was inferior to White (p= 0.0339), Asians (p=0.001), and other races (p=0.0011); Figure 2 and Table 3. For the time period 1996-2003, there was no difference in survival across races (p-value=0.7599); Figure 3 and Table 3. For the time period of 2004-2011, survival of Black patients was similar to White (p-value=1) but again inferior to Asian (p-value=0.05) and other races (p-value=0.09); Figure 4 and Table 3. Across the entire time period of 1998-2011, the survival of Black patients was inferior to White (Chi-square=6.59 and p-value=0.0084); Figure 5. The survival gap between Black and White patients seems to be obliterated in subsequent; "1996 - 2003" and "2004 - 2011" vs 1988-1995 (Figures 3 and 4) due to improvements in survival of Black patients over time (Figure 6) while the survival of White patients remained rather steady over time (Figure 7). Conclusions: Our study demonstrated that Black race was significantly correlated with poorer survival in patients with MF. The etiology of this poorer prognosis can be related to access to medical care, socioeconomic disparities, or possibly difference in disease biology and immune response. Despite the persistent pattern of lower survival across all time periods, the gap in survival between White and Black races seems to be narrowing overtime. Figure 1 Figure 1. Disclosures William: Dova Pharmaceuticals: Research Funding; Incyte: Research Funding; Kyowa Kirin: Consultancy; Merck: Research Funding; Guidepoint Global: Consultancy.

scholarly journals Comparative Effectiveness and Safety of Extended Anticoagulant Therapy Among Medicare Beneficiaries with Venous Thromboembolism

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 178-178
Author(s):  
Haesuk Park ◽  
Hye-Rim Kang ◽  
Pei-Lin Huang ◽  
Wei-Hsuan Lo-Ciganic ◽  
Eric A Dietrich ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Research Program ◽  
Initial Treatment ◽  
Research Funding ◽  
Oral Anticoagulants ◽  
Medicare Beneficiaries ◽  
Bleeding Events ◽  
Extended Treatment ◽  
Recurrent Vte ◽  
Program Research

Abstract Introduction: Approximately 30% of patients with venous thromboembolism (VTE) experience a recurrence within 10 years of the initial event with their recurrence risk peaking during the first 6-12 months. Two large randomized clinical trials AMPLIFY-EXT and PADIS-PE reported that extended treatment with apixaban and warfarin beyond 6 months of initial treatment reduced recurrent VTE without increasing the rate of major bleeding compared to placebo, respectively. Little is known about real-world effectiveness and safety of extended oral anticoagulation beyond 6 months of initial treatment for Medicare beneficiaries with VTE, despite the fact that VTE disproportionately affects the elderly. We assessed the effectiveness and safety of extended use of apixaban and warfarin beyond 6 months of initial treatment for prevention of recurrent VTE and adverse major bleeding events among Medicare beneficiaries with newly diagnosed VTE. Methods: A retrospective cohort study using 2014-2018 Medicare data (5% samples in 2014-2016 and 15% samples of Medicare beneficiaries in 2017-2018) was conducted for patients aged ≥18 years with a diagnosis of deep vein thrombosis or pulmonary embolism ascertained from inpatient claims. Patients were included if they initiated anticoagulants within 30 days of their first VTE diagnosis, completed 6 months of therapy defined as ≥83% proportion days covered with oral anticoagulants during the initial 6-month period, and received extended treatment with either apixaban or warfarin or no extended therapy. We compared the risks of recurrent VTE and major bleeding between apixaban, warfarin, and no treatment groups. To adjust for differences in baseline characteristics and clinical factors (e.g., HAS-BLED score, active cancer, and provoked VTE) between groups, we used the stabilized inverse probability treatment weighting (IPTW) method. Follow-up continued until the occurrence of the first event, switch to the comparator, disenrollment, death, or end of the study period. Multivariable Cox proportional hazards modeling with IPTW was used to obtain adjusted hazard ratios (aHR) and 95% confidence intervals (95%CI). Results: The study cohort (mean age=74 ±12 years, 40% male, 76% White) consisted of 2,315 users of extended apixaban treatment (83% with 5 mg twice a day and 17% with 2.5 mg twice a day; mean duration=6.2 months), 2,757 users of extended warfarin treatment (mean duration=8.2 months), and 2,328 patients with no extended treatment following completion of an initial 6 months of anticoagulant treatment. The incidence rates of recurrent VTE were 0.42, 1.73, and 1.72 per 100 person-years, and those of major bleeding were 2.28, 3.62, and 1.43 per 100 person-years in the apixaban, warfarin, and no treatment groups, respectively (Table 1). Compared to no extended treatment, the use of apixaban was associated with an 80% decreased risk of recurrent VTE (aHR=0.19, 95%CI=0.06-0.55) without increasing the risk of major bleeding (aHR=1.19, 95%CI=0.65-2.19); the use of warfarin did not lower the risk of recurrent VTE (aHR=0.75, 95%CI=0.42-1.37) but increased the risk of major bleeding (aHR=1.92, 95%CI=1.13-3.25). Compared to the use of warfarin, the use of apixaban was associated with a decreased risk of recurrent VTE (aHR=0.26, 95% CI=0.09-0.76) and no difference in major bleeding risk (aHR=0.61, 95%CI=0.36-1.06). These findings remained consistent in subgroup (e.g., patients with provoked vs. unprovoked VTE, patients with active cancer vs. those without, and patients with chronic kidney diseases vs. those without) and sensitivity analyses (e.g., ≥92% proportion days covered with oral anticoagulants during the initial 6-month period). Conclusions: Compared to no extended therapy, extended anticoagulation with apixaban was associated with a reduced risk of recurrent VTE without increasing the risk of major bleeding, whereas warfarin did not lower risk of recurrent VTE but increased the risk of major bleeding among Medicare beneficiaries with VTE. In the head-to-head comparison, the use of apixaban was more effective than warfarin in preventing recurrent VTE, without increasing the risk of major bleeding events. Our findings suggest that apixaban is an effective and safer option for extended treatment of VTE when compared to warfarin or no treatment among Medicare beneficiaries with VTE. Figure 1 Figure 1. Disclosures Park: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Kang: BMS/Pfizer Alliance American Thrombosis InvestigatorInitiated Research Program: Research Funding. Huang: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Lo-Ciganic: MERCK: Research Funding; BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Dietrich: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding. Murphy: North American Thrombosis Foundation: Honoraria. DeRemer: BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program: Research Funding; Portola Pharmaceuticals: Current equity holder in publicly-traded company; BMS advisory board attendee: Honoraria.

scholarly journals Efficacy and Safety of Direct Oral Factor Xa Inhibitors in 795 Morbidly Obese Patients

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 423-423 ◽  
Author(s):  
Margarita Kushnir ◽  
Yun Choi ◽  
Ruth Eisenberg ◽  
Devika Rao ◽  
Seda Tolu ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Research Funding ◽  
Factor Xa ◽  
Factor Xa Inhibitors ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Prescription Date ◽  
Recurrent Vte

Abstract Background: Studies of acute venous thromboembolism (VTE) and non-valvular atrial fibrillation (AF) have shown comparable therapeutic efficacy and similar or lower bleeding risk for direct oral anticoagulants (DOACs) compared to warfarin. Because the representation of morbidly obese patients (BMI ≥40 kg/m2) in pivotal clinical trials has been minimal, efficacy and safety of DOACs in this population are unclear. Our goal was to investigate whether direct oral factor Xa inhibitors, apixaban and rivaroxaban, are as effective and safe as warfarin in morbidly obese (BMI ≥40) patients. Methods: Using our institutional database, we identified all adult patients at Montefiore Medical Center with BMI ≥40 who were started on anticoagulation with apixaban, rivaroxaban or warfarin, for either AF or VTE, between March 1, 2013 and March 1, 2017. We reviewed charts to obtain detailed information on patient demographics and to document clinical outcomes of recurrent VTE, ischemic stroke (CVA) and bleeding from the first prescription date to the earliest of a thrombotic event, discontinuation of medication, death, or June 30, 2017. VTE and CVA episodes were confirmed by imaging (compression sonography, CT scans, ventilation/perfusion scans, MRIs). Bleeding events were classified according to criteria from the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Analyses were stratified by anticoagulation indication. Chi-squared tests or Fisher's exact tests were used to assess statistical significance of the differences in VTE, CVA and bleeding rates between anticoagulant cohorts. Differences in times from first prescription date to VTE, CVA and bleeding were analyzed with Kaplan-Meier curves, Log-rank tests, and Cox proportional hazards models. Data were adjusted for age, CHA2DS2-VASc, and Charlson scores. Subgroup analyses were performed for patients with BMI ≥50 kg/m2. Results: Data on 795 patients were collected. In 366 patients with a history of VTE, the rates of recurrent VTE were low and comparable among the apixaban, rivaroxaban and warfarin cohorts [1/47 (2.1%), 3/152 (2%), and 2/167 (1.2%), respectively, p=0.74]. In the subgroup of individuals with BMI ≥50 kg/m2 (n=92), none of the 40 DOAC patients had recurrent VTE. The rates of clinically relevant bleeding, including major bleeding, among VTE patients, were comparable between the three cohorts. Among the 429 patients with AF, stroke rates were also low and similar among anticoagulant cohorts [1/103 (1%) for apixaban, 4/174 (2.3%) for rivaroxaban, and 2/152 (1.3%) for warfarin, p=0.71]. CVAs were similarly rare in patients with BMI ≥50 (1/19 patients on apixaban, 0/37 on rivaroxaban and 1/44 patients on warfarin). In the AF sample, there was no statistically significant difference in the rate of bleeding, including major bleeding, among the 3 cohorts. In an analysis with combined DOAC cohort (apixaban + rivaroxaban vs. warfarin), the recurrent VTE and stroke rates were still low and comparable. There were more major bleeding events in AF patients on warfarin than the combined DOAC cohort (7.9% vs. 2.9%, p=0.02), a finding that became non-significant when adjusted for age, CHA2DS2-VASc, and Charlson scores (p=0.06). The rates of bleeding, including major bleeding, were comparable among the three anticoagulants in both VTE and AF patients with BMI ≥50. Conclusions: Our study is the largest study examining morbidly obese patients on DOACS and provides further evidence of comparable efficacy and safety of the direct oral anti-Xa inhibitors, compared to warfarin, in morbidly obese patients with AF and VTE. Disclosures Kushnir: Janssen: Research Funding. Billett:Bayer: Consultancy; Janssen: Research Funding.

scholarly journals Trial in Progress: Feasibility and Validation Study of the LSC17 Score in Acute Myeloid Leukemia Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2682-2682
Author(s):  
Tracy Murphy ◽  
Stanley W.K. Ng ◽  
Tong Zhang ◽  
Ian King ◽  
Andrea Arruda ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Phase 1 ◽  
Turnaround Time ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Advisory Committees ◽  
Cancer Centre

Background: AML is driven by a small subpopulation of leukemia stem cells (LSCs), which possess stem-cell properties such as quiescence and self-renewal that are linked to therapy resistance and relapse. The LSC17 score was derived from genes differentially expressed between functionally validated LSC+ and LSC- cell fractions from 78 AML patients. The LSC17 score was strongly associated with survival in 4 independent cohorts of AML patients treated with curative intent (n = 908), and accurately predicted initial response. Patients with high LSC17 scores had poor outcomes with standard treatment strategies. The LSC17 score remained highly significant in multivariate analyses, independent of commonly used prognostic factors. A critical advantage of the LSC17 test over cytogenetic analysis is its rapid turnaround time (24-48h on a NanoString platform), providing clinicians with a powerful tool for upfront risk stratification. To date, no RNA-based, stem cell-derived score has been transitioned into a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. Study design and methods: The study consists of 2 phases. Phase 1 aims to validate the assay in a CLIA certified laboratory setting. Phase 2 aims to determine prospectively the feasibility and prognostic power of LSC17 score testing in newly diagnosed AML patients in the real-world setting. Clinical endpoints include primary induction failure rate, relapse free survival and overall survival. All patients with a suspected diagnosis of de novo or secondary AML, who are deemed fit and appropriate by their treating physician to undergo intensive induction chemotherapy, are considered for this study. Patients who received any prior anti-leukemia treatments (except hydroxyurea) and patients with a confirmed diagnosis of acute promyelocytic leukemia are excluded. Current participating centres include Princess Margaret Cancer Centre (Toronto), Juravinski Cancer Centre (Hamilton), and The Ottawa Hospital Cancer Centre (Ottawa). Pre-study sample size analysis suggests that 150 patients will be required to demonstrate a hazard ratio for death of 2.3 between patients with a high and low LSC17 score (α = 0.05, power = 0.8). The survival for the high and low LSC17 score groups will be compared using the Cox proportional hazards model. Traditional risk stratification will also be tested within a Cox proportional hazards model. Phase 1 of the study has been completed and several key quality control measures have been created. Initial derivation and validation of the LSC17 score was performed using standard chemistry on the NanoString platform; for CLIA lab validation, the assay was transitioned to Elements© chemistry, which does not require custom codeset manufacture by NanoString. The original AML reference cohort was retested using Elements© chemistry to derive an absolute median threshold for prospective LSC17 score determination in individual patients. The lab validation process compared and found no difference in LSC17 scores between samples processed by Ficoll or collected in Paxgene for ease of processing. A standardised quality assurance (QA) process was completed to identify optimal sample requirements as well as specimen storage conditions, score stability during sample storage and turnaround time for testing. An algorithm has been created using the laboratory information system to allow standardised and rapid calculation of the LSC17 score from NanoString nCounter output data. The LSC17 score can be tested on peripheral blood or bone marrow, although bone marrow samples are preferred for patients with very low peripheral blast counts. Samples are ideally stored in RNA Paxgene tubes for RNA stability and to maximize RNA yield. The prospective phase of the study (Phase 2) opened in April 2018 and as of June 2019, 233 patients have been enrolled, of which 120 received induction chemotherapy. 54 patients were excluded due to an alternative diagnosis or failed QA. The remaining patients had non-intensive therapy based on patient choice. Standard prognostic markers including cytogenetics, molecular studies and targeted sequencing using a 49-gene AML panel are performed in parallel to the LSC17 score. Treatment was administered according to physician preference, based on patient history and results of standard prognostic assays, when available. The study continues to recruit and is open to collaborations in other centres. Disclosures Ng: Celgene: Research Funding. Leber:Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz: Honoraria, Membership on an entity's Board of Directors or advisory committees; Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Sabloff:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas Pharma Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees; ASTX: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees; Actinium Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Canada: Research Funding. Minden:Trillium Therapetuics: Other: licensing agreement. Wang:NanoString: Other: Travel and accommodation; Trilium therapeutics: Other: licensing agreement, Research Funding; Pfizer AG Switzerland: Honoraria, Other: Travel and accommodation; Pfizer International: Honoraria, Other: Travel and accommodation.

scholarly journals Prognostic significance of p16, p53, Bcl-2, and Bax in oral and oropharyngeal squamous cell carcinoma

2014 ◽  
Vol 8 (2) ◽  
pp. 255-261
Author(s):  
Paramee Thongsuksai ◽  
Kowit Pruegsanusak ◽  
Pleumjit Boonyaphiphat
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
P53 Expression

Abstract Background: The proteins p16, p53, Bcl-2, and Bax are important cell cycle and apoptotic regulators involved in carcinogenesis and found to have prognostic significance in various cancers. However, the data for squamous cell carcinoma of oral cavity (OSCC) and of oropharynx (OPSCC) are conflicting. Objective: We sought to determine if expression of p16, p53, Bcl-2, and Bax expression are associated with 5-year overall survival (OS) of patients with OSCC and OPSCC. Methods: One-hundred thirty-seven cases of OSCC and 140 cases of OPSCC diagnosed from January 2002 to December 2004 at Songklanagrind Hospital, Songkhla, Thailand, were analyzed using a Cox proportional hazards model for 5-year OS in relation to immunohistochemical detection of Bcl-2, Bax, p53, and p16 proteins. Results: The frequencies of p16, p53, Bcl-2, and Bax expression in OSCC were 13%, 45%, 4%, and 66%, and in OPSCC were 18%, 53%, 22%, and 75%, respectively. In univariate analysis, clinical variables including T stage, N stage and treatment were significantly associated with survival. In multivariate Cox regression, Bax overexpression was significantly associated with poor survival both in OSCC (HR 1.77, 95% CI 1.04-3.01) and in OPSCC (HR 2.21, 95% CI 1.00-4.85). We found no significant association of p16, Bcl-2, and p53 expression with survival. Conclusion: The expression pattern of p16, p53, Bcl-2, and Bax are similar in OSCC and OPSCC. Only Bax expression has prognostic significance for both tumor sites.

scholarly journals NCOG-33. HEMATOLOGIC PREDICTORS OF OUTCOMES IN GLIOBLASTOMA TREATED WITH SURGERY AND CHEMORADIATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii136-ii136
Author(s):  
Nicholas Damico ◽  
Theresa Elder ◽  
Michael Kharouta ◽  
Anthony Sloan ◽  
Amber Kerstetter-Fogle ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Continuous Variables ◽  
Surgical Biopsy ◽  
Platelet Counts ◽  
Cell Counts ◽  
Time Point

Abstract BACKGROUND There are conflicting reports regarding the prognostic value of platelet and other blood counts in glioblastoma. However, few series have looked at all hematologic parameters simultaneously. METHODS We performed a retrospective chart review of patients diagnosed with supratentorial glioblastoma from 2014-2019 who started conventional chemoradiation following initial surgical biopsy and/or resection. Hematologic parameters were collected at baseline, in the preoperative and postoperative periods and at the initiation and completion of chemoradiation. This included platelet counts, hemoglobin levels, white blood cell counts (WBC), neutrophil and lymphocyte counts with neutrophil:lymphocyte (NLR) and platelet:lymphocyte ratios (PLR) calculated at each time point. Cox regression was performed to assess the association between each hematologic parameter and both overall survival (OS) and progression free survival (PFS). A multivariate Cox proportional hazards model adjusted for all hematologic parameters, age, sex, race and KPS was generated for each time point. All hematologic parameters were modeled as continuous variables. RESULTS A total of 58 patients met inclusion criteria. 18 were female and 40 male. The median age was 59.5 (range 43-82). Median follow up for all patients was 15.3 months. A total of 52 patients completed radiation therapy and 18 completed 6 cycles of adjuvant chemotherapy. Hemoglobin and neutrophil counts at the conclusion of chemoradiation were associated with OS and PFS on univariate and multivariate analyses. The HR for OS were 0.74 (95% CI 0.5807-0.9313) and 1.28 (1.143-1.441) respectively. The HR for PFS were 0.70 (0.5531-0.8881) and 1.16 (1.05-1.271) respectively. Postoperative lymphocyte and platelet counts at initiation of chemoradiation were both associated with OS with unadjusted HR of 3.2 (1.037-9.960) and HR of 0.99 (0.9898-0.9999) respectively, which remained significant on multivariate analysis. However, neither were associated with PFS. CONCLUSION Several hematologic parameters are associated with glioblastoma outcomes in these initial analyses. Further analyses with additional patients are ongoing.

scholarly journals A Randomized, Open-Label, Blinded Outcome Assessment Trial Evaluating the Efficacy and Safety of LMWH/Edoxaban Versus Dalteparin for Venous Thromboembolism Associated with Cancer: Hokusai VTE-Cancer Study

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. LBA-6-LBA-6
Author(s):  
Gary E. Raskob ◽  
Nick Van Es ◽  
Peter Verhamme ◽  
Marc Carrier ◽  
Marcello Di Nisio ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Research Funding ◽  
Primary Outcome ◽  
Bleeding Events ◽  
Open Label ◽  
Advisory Committees ◽  
Once Daily ◽  
Vein Thrombosis ◽  
Bayer Healthcare ◽  
Recurrent Vte

Abstract On behalf of the Hokusai VTE Cancer Investigators The treatment of cancer-associated venous thromboembolism (VTE) is challenging because these patients are at increased risk of both recurrent VTE and major bleeding. Low-molecular-weight heparin (LMWH) treatment is standard care for these patients, but requires daily subcutaneous injections. Guidelines recommend LMWH treatment for 6 months, but the risk-benefit beyond this time is uncertain. Direct oral anticoagulants are used for the treatment of VTE in patients without cancer, but their role in patients with cancer- associated VTE is uncertain. In this randomized, open-label non-inferiority trial, cancer patients with acute symptomatic or incidental VTE were assigned to receive LMWH for a minimum of 5 days followed by the oral factor Xa inhibitor edoxaban at a dose of 60 mg once daily (or 30 mg once daily in patients with a creatinine clearance of 30 to 50 ml per minute or a body weight below 60 kg), or subcutaneous dalteparin 200 units per kg once daily for one month followed by 150 units per kg thereafter. Patients received these regimens for up to 12 months. The primary outcome was the composite of the first recurrent VTE or major bleeding event during follow-up for 12 months. Secondary outcomes included recurrent VTE and major bleeding analyzed separately, and survival free of recurrent VTE or major bleeding. The study hypothesis was that edoxaban would be noninferior to dalteparin for the primary outcome with an upper 95% confidence interval [CI] for the hazard ratio below 1.5, and a two-sided alpha of 0.05. All outcomes were independently adjudicated by a committee without knowledge of treatment allocation. This committee also assessed the clinical severity of major bleeding events using categorical criteria defined a priori (categories 1 to 4). From July 2015 through December 2016 a total of 1050 patients were enrolled at 114 centers in 13 countries; 525 were randomized to edoxaban and 525 to dalteparin. At entry, pulmonary embolism with or without deep-vein thrombosis was present in 657 patients (63%) while the remainder had isolated deep-vein thrombosis. Of the 1050 patents, 706 (67%) had symptomatic VTE and the rest were incidental. Active cancer at entry was present in 97% of the patients and 53% had metastatic disease. 1046 patients were included in the modified-intention-to-treat analysis. The primary outcome occurred in 67 of 522 patients (12.8%) in the edoxaban group compared with 71 of 524 patients (13.5%) in the dalteparin group (hazard ratio with edoxaban, 0.97; 95% CI, 0.70 to 1.36; P = 0.0056 for noninferiority) for a risk difference (edoxaban minus dalteparin) of - 0.7% (95% CI, - 4.8 to 3.4). The difference in risk for recurrent VTE was -3.8 % (95% CI, -7.1 to -0.4), whereas the corresponding difference in risk for major bleeding was 3.1% (95% CI, 0.5 to 5.7). The frequencies of severe major bleeding events (categories 3 and 4) were similar during treatment with edoxaban or dalteparin (12 patients in each group respectively). Survival at 12 months free of recurrent VTE and major bleeding in the edoxaban and dalteparin groups was similar (55.0% and 56.5% respectively). Oral edoxaban for up to 12 months is noninferior to subcutaneous dalteparin for the treatment of cancer-associated VTE. Disclosures Raskob: BMS: Consultancy, Honoraria; Eli Lilly: Consultancy; Janssen: Consultancy; Johnson and Johnson: Consultancy; Pfizer: Consultancy, Honoraria; Portola: Consultancy; Boehringer-Ingelheim: Consultancy; Medscape: Honoraria; Bayer Healthcare: Consultancy; Daiichi Sankyo: Consultancy, Honoraria. Van Es:Daiichi Sankyo: Honoraria; Pfizer: Honoraria. Verhamme:Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Bayer Healthcare: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Portola: Consultancy; Medscape: Honoraria; Leo: Honoraria, Research Funding; Sanofi Aventis: Research Funding; Medtronic: Honoraria, Membership on an entity's Board of Directors or advisory committees. Carrier:Daiichi Sankyo: Consultancy, Honoraria; BMS: Consultancy, Research Funding; Leo: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria. Di Nisio:Daiichi: Consultancy, Honoraria. Garcia:Daiichi Sankyo: Honoraria, Research Funding; BMS: Consultancy; Boehringer Ingelheim: Consultancy; Janssen: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria; Medscape: Honoraria; Incyte: Consultancy, Honoraria, Research Funding. Grosso:Daiichi Sankyo: Employment. Kakkar:Daiichi Sankyo: Consultancy, Honoraria; Bayer Healthcare: Consultancy, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi SA: Consultancy, Honoraria; Verseon: Consultancy, Honoraria. Kovacs:Daiichi Sankyo: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Bayer: Honoraria; Bristol Myers Squibb: Research Funding. Mercuri:Daiichi Sankyo: Employment, Patents & Royalties: pending properties of edoxaban . Meyer:BMS Pfizer: Research Funding; Leo: Other: travel support; Stago: Other: travel support. Segers:Ionis: Research Funding; Daiichi Sankyo: Research Funding; Janssen: Research Funding. Shi:Daiichi Sankyo: Employment. Wang:Daiichi Sankyo: Honoraria. Yeo:Daiichi Sankyo: Honoraria, Research Funding; Bayer Healthcare: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Leo: Consultancy, Honoraria. Zhang:Daiichi Sankyo: Employment. Zwicker:Daiichi Sankyo: Honoraria; Quercegen Pharma: Research Funding; Parexel: Consultancy. Weitz:Daiichi-Sankyo: Consultancy, Honoraria; Ionis Pharmaceuticals: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis Pharmaceuticals: Consultancy, Honoraria; Merck & Co., Inc.: Consultancy, Honoraria; Pfizer, Inc.: Consultancy, Honoraria; Portola Pharmaceuticals: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Medscape: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy; Bayer HealthCare Pharmaceuticals: Consultancy, Honoraria. Büller:Daiichi Sankyo: Consultancy, Honoraria; Bayer: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Portola: Consultancy; Medscape: Honoraria; Eli Lilly: Consultancy; Sanofi Aventis: Consultancy; Ionis: Consultancy.

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