Matching-adjusted indirect comparison (MAIC) of relative efficacy for brigatinib vs. ceritinib and alectinib in crizotinib-resistant anaplastic lymphoma kinase (ALK+) non-small cell lung cancer (NSCLC).

e20675 Background: Brigatinib (BRG), ceritinib (CER), and alectinib (ALEC) are second-generation ALK inhibitors developed for crizotinib (CRZ)-resistant ALK+ NSCLC. No randomized trial has directly compared the efficacy of these treatments. The goal of this analysis was to use an MAIC to indirectly compare progression-free survival (PFS) and overall survival (OS) for BRG vs CER and BRG vs ALEC in CRZ-resistant ALK+ NSCLC patients (pts). Methods: This analysis used pt-level data from arm B (180 mg qd with a 7-day lead-in at 90 mg, n=110) of the ALTA trial for BRG and published summary data from ASCEND-1/ASCEND-2 and NP28673 trials for CER and ALEC, respectively. PFS and OS curves from published data were digitized to generate virtual pt-level data for estimation of event rates. Pts in ALTA were assigned weights so that their weighted mean baseline characteristics matched baseline characteristics in each of ASCEND-1, ASCEND-2, and NP28673. Relative treatment effects pre- and post-matching were estimated using Cox proportional hazards models. Results: Prior to matching, baseline imbalances were noted in ECOG PS 2, prior chemotherapy, Asian race, smoking status, and best prior response to CRZ among trials. Weighting reduced effective sample sizes (ESSs) for ALTA pts in the matched comparisons. Relative efficacy results were robust and did not appreciably change after adjusting for the prognostic factors (Table 1). Conclusions: Both before and after matching, BRG had significantly longer PFS compared to CER and ALEC, significantly longer OS than CER, and a trend toward longer OS than ALEC. [Table: see text]

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Efficacy outcomes of nivolumab + cabozantinib versus pembrolizumab + axitinib in patients with advanced renal cell carcinoma (aRCC): Matching-adjusted indirect comparison (MAIC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4578 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4578-4578

Author(s):

Bradley Alexander McGregor ◽

Daniel M. Geynisman ◽

Mauricio Burotto ◽

Camillo Porta ◽

Cristina Suarez Rodriguez ◽

...

Keyword(s):

Proportional Hazards ◽

Objective Response ◽

Indirect Comparison ◽

Progression Free Survival ◽

Wald Test ◽

Patient Characteristics ◽

Cox Proportional Hazards ◽

Published Data ◽

Cox Proportional Hazards Models

4578 Background: Nivolumab in combination with cabozantinib (N+C) has demonstrated significantly improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS), compared with sunitinib as a first-line (1L) treatment for aRCC in the phase 3 CheckMate (CM) 9ER trial. As there are no head-to-head trials comparing N+C with pembrolizumab in combination with axitinib (P+A), this study compared the efficacy of N+C with P+A as 1L treatment in aRCC. Methods: An MAIC was conducted using individual patient data on N+C (N = 323) from the CM 9ER trial (median follow-up: 23.5 months) and published data on P+A (N = 432) from the KEYNOTE (KN)-426 trialof P+A (median follow-up: 30.6 months). Individual patients within the CM 9ER trial population were reweighted to match the key patient characteristics published in KN-426 trial, including age, gender, previous nephrectomy, International Metastatic RCC Database Consortium risk score, and sites of metastasis. After weighting, hazards ratios (HR) of PFS, duration of response (DoR), and OS comparing N+C vs. P+A were estimated using weighted Cox proportional hazards models, and ORR was compared using a weighted Wald test. All comparisons were conducted using the corresponding sunitinib arms as an anchor. Results: After weighting, patient characteristics in the CM 9ER trial were comparable to those in the KN-426 trial. In the weighted population, N+C had a median PFS of 19.3 months (95% CI: 15.2, 22.4) compared to a median PFS of 15.7 months (95% CI: 13.7, 20.6) for P+A. Using sunitinib as an anchor arm, N+C was associated with a 30% reduction in risk of progression or death compared to P+A, (HR: 0.70, 95% CI: 0.53, 0.93; P = 0.015; table). In addition, N+C was associated with numerically, although not statistically, higher improvement in ORR vs sunitinib (difference: 8.4%, 95% CI: -1.7%, 18.4%; P = 0.105) and improved DoR (HR: 0.79; 95% CI: 0.47, 1.31; P = 0.359). Similar OS outcomes were observed for N+C and P+A (HR: 0.99; 95% CI: 0.67, 1.44; P = 0.940). Conclusions: After adjusting for cross-trial differences, N+C had a more favorable efficacy profile compared to P+A, including statistically significant PFS benefits, numerically improved ORR and DoR, and similar OS.[Table: see text]

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The influence of institutional head and neck cancer (HNC) clinical trial accrual on overall survival (OS): An analysis of RTOG 0129.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.5530 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 5530-5530

Author(s):

Evan John Wuthrick ◽

Qiang Zhang ◽

Mitchell Machtay ◽

K. Kian Ang ◽

David Ira Rosenthal ◽

...

Keyword(s):

Proportional Hazards ◽

Smoking Status ◽

Performance Status ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Independent Effect ◽

Locoregional Failure ◽

Risk Of Death ◽

Hpv Status ◽

N Stage

5530 Background: NCCN recommends HNC patients (pts) be treated by providers with experience in HNC management. Whether treatment by experienced providers (measured by no. of pts treated) is associated with HNC survival outcome is unknown. Methods: Analysis included 471 pts in RTOG 0129 with stage III-IVa HNC with known tumor HPV and smoking status randomized to cisplatin concurrent with standard or accelerated fractionation radiotherapy (RT). Participating centers were stratified into pt accrual tertiles (ATs) to 21 RTOG HNC trials from 1997-2002. As a surrogate for experience, we investigated the independent effect of AT on OS and progression-free survival (PFS) in multivariable cox proportional hazards models. Results: Median follow up was 4.8 yrs (range 1.1 - 6.5). In Kaplan-Meier analysis, OS and PFS for pts at centers in the two lower AT (low accruing centers [LAC]) were similar and compared to the upper AT (high accruing centers [HAC]). Median accrual in LAC vs HAC was 11 vs 82 pts. Pts treated at LAC and HAC had similar age, HPV status, pack-years, N stage, comorbidities and study arm assignment (SAA), but pts at LAC had better performance status (PS)(Zubrod 0; 62% vs 52%; p=0.04), fewer T4 tumors (27% vs. 35%; p=0.05) and were more likely uninsured (12% vs 4%; p=0.009). Compared to HAC, LAC pts had significantly worse OS, (5 yr 51.0% vs 69.1%; p = 0.002), and PFS (5 yr 42.7% vs 61.8%; p = 0.001) and more locoregional failure (5 yr 36.4% vs 20.8%; p <0.001). Treatment at LAC was associated with ~90% increase in risk of death (OS HR 1.91, 95%CI 1.37-2.65) and progression (PFS HR 1.89, 95%CI 1.39-2.56) when compared to pts treated at HAC, after adjustment for age, PS, pack-years, T and N stage, SAA and HPV status. Acute and chronic toxicities, RT dose, fractions, and treatment duration did not differ for pts at LAC vs HAC. RT at LAC was more likely than HAC to differ from protocol (18% [16.8% acceptable variation {AV}, 1.2% unacceptable deviation {UD}] vs 6% [4.7% AV, 1.3% UD]; p<0.001). Conclusions: Pts with HNC treated at LAC in RTOG trials were associated with significantly worse survival outcomes compared to pts treated at HAC.

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PETCO2 gradient: a novel prognostic parameter in cardiopulmonary exercise testing

European Heart Journal ◽

10.1093/ehjci/ehaa946.1077 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

I.D Poveda Pinedo ◽

I Marco Clement ◽

O Gonzalez ◽

I Ponz ◽

A.M Iniesta ◽

...

Keyword(s):

Exercise Testing ◽

Proportional Hazards ◽

Cardiopulmonary Exercise Testing ◽

Cox Proportional Hazards ◽

Prognostic Parameter ◽

Cardiopulmonary Exercise ◽

Proportional Hazards Regression ◽

Kaplan Meier ◽

Baseline Characteristics ◽

The Difference

Abstract Background Previous parameters such as peak VO2, VE/VCO2 slope and OUES have been described to be prognostic in heart failure (HF). The aim of this study was to identify further prognostic factors of cardiopulmonary exercise testing (CPET) in HF patients. Methods A retrospective analysis of HF patients who underwent CPET from January to November 2019 in a single centre was performed. PETCO2 gradient was defined by the difference between final PETCO2 and baseline PETCO2. HF events were defined as decompensated HF requiring hospital admission or IV diuretics, or decompensated HF resulting in death. Results A total of 64 HF patients were assessed by CPET, HF events occurred in 8 (12.5%) patients. Baseline characteristics are shown in table 1. Patients having HF events had a negative PETCO2 gradient while patients not having events showed a positive PETCO2 gradient (−1.5 [IQR −4.8, 2.3] vs 3 [IQR 1, 5] mmHg; p=0.004). A multivariate Cox proportional-hazards regression analysis revealed that PETCO2 gradient was an independent predictor of HF events (HR 0.74, 95% CI [0.61–0.89]; p=0.002). Kaplan-Meier curves showed a significantly higher incidence of HF events in patients having negative gradients, p=0.002 (figure 1). Conclusion PETCO2 gradient was demonstrated to be a prognostic parameter of CPET in HF patients in our study. Patients having negative gradients had worse outcomes by having more HF events. Time to first event, decompensated heart Funding Acknowledgement Type of funding source: None

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The Relationship of Diabetes Mellitus to Efficacy of Immune Checkpoint Inhibitors in Patients with Advanced Non-Small Cell Lung Cancer

Oncology ◽

10.1159/000516671 ◽

2021 ◽

pp. 1-7

Author(s):

Oded Jacobi ◽

Yosef Landman ◽

Daniel Reinhorn ◽

Oded Icht ◽

Michal Sternschuss ◽

...

Keyword(s):

Diabetes Mellitus ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Proportional Hazards ◽

Checkpoint Inhibitors ◽

Negative Relationship ◽

Progression Free Survival ◽

Significant Negative Correlation ◽

Cox Proportional Hazards ◽

Diabetic Patients

Introduction: Immune checkpoint inhibitors (ICI) are the new standard therapy in patients with metastatic NSCLC (mNSCLC). Metformin, previously associated with improved chemotherapy efficacy in diabetic and nondiabetic cancer patients, was recently associated with increased ICI efficacy. In this study, we aimed to explore the correlations between diabetes mellitus (DM), metformin use, and benefit from ICI in mNSCLC patients. Methods: All mNSCLC patients treated with ICI in our center between February 2015 and April 2018 were identified. Demographic and clinical data were extracted retrospectively. Cox proportional hazards regression, t tests, and χ2 tests were employed to evaluate associations of progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and disease control rate (DCR), with DM status, metformin use, and HbA1c levels, as appropriate. Results: Of 249 mNSCLC patients treated with ICI, 57 (22.8%) had DM. Thirty-seven (64.9% of all diabetic patients) patients were treated with metformin. A significant negative correlation of DM with PFS and OS was demonstrated (HR 1.5 [1.01–2.06], p = 0.011, and HR 1.5 [1.08–2.08], p = 0.017, respectively). Metformin exposure had no significant correlation with PFS or OS in diabetic mNSCLC patients (HR 1.08 [0.61–1.93], p = 0.79, and HR 1.29 [0.69–2.39], p = 0.42, respectively). There were no differences between groups with respect to ORR and DCR. Conclusion: Our data show a potential negative relationship between DM and ICI efficacy in mNSCLC patients. In contrast to reports with chemotherapy, we found no positive relationship between metformin use and ICI therapy in diabetic patients with mNSCLC. Further studies are needed to evaluate the effect of metformin in nondiabetic mNSCLC patients.

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Pre-diagnosis neutrophil-to-lymphocyte ratio and mortality in individuals who develop lung cancer

Cancer Causes & Control ◽

10.1007/s10552-021-01469-3 ◽

2021 ◽

Author(s):

Laurie Grieshober ◽

Stefan Graw ◽

Matt J. Barnett ◽

Gary E. Goodman ◽

Chu Chen ◽

...

Keyword(s):

Lung Cancer ◽

Proportional Hazards ◽

Smoking Status ◽

Cox Proportional Hazards ◽

Neutrophil To Lymphocyte Ratio ◽

Blood Draw ◽

Lymphocyte Ratio ◽

Cox Proportional Hazards Models ◽

Inflammatory Profile ◽

Heavy Smokers

Abstract Purpose The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that has been reported to be associated with survival after chronic disease diagnoses, including lung cancer. We hypothesized that the inflammatory profile reflected by pre-diagnosis NLR, rather than the well-studied pre-treatment NLR at diagnosis, may be associated with increased mortality after lung cancer is diagnosed in high-risk heavy smokers. Methods We examined associations between pre-diagnosis methylation-derived NLR (mdNLR) and lung cancer-specific and all-cause mortality in 279 non-small lung cancer (NSCLC) and 81 small cell lung cancer (SCLC) cases from the β-Carotene and Retinol Efficacy Trial (CARET). Cox proportional hazards models were adjusted for age, sex, smoking status, pack years, and time between blood draw and diagnosis, and stratified by stage of disease. Models were run separately by histotype. Results Among SCLC cases, those with pre-diagnosis mdNLR in the highest quartile had 2.5-fold increased mortality compared to those in the lowest quartile. For each unit increase in pre-diagnosis mdNLR, we observed 22–23% increased mortality (SCLC-specific hazard ratio [HR] = 1.23, 95% confidence interval [CI]: 1.02, 1.48; all-cause HR = 1.22, 95% CI 1.01, 1.46). SCLC associations were strongest for current smokers at blood draw (Interaction Ps = 0.03). Increasing mdNLR was not associated with mortality among NSCLC overall, nor within adenocarcinoma (N = 148) or squamous cell carcinoma (N = 115) case groups. Conclusion Our findings suggest that increased mdNLR, representing a systemic inflammatory profile on average 4.5 years before a SCLC diagnosis, may be associated with mortality in heavy smokers who go on to develop SCLC but not NSCLC.

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Impact of Pathological Stratification on the Clinical Outcomes of Advanced Well-Differentiated/Dedifferentiated Liposarcoma Treated with Trabectedin

Cancers ◽

10.3390/cancers13061453 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1453

Author(s):

Chiara Fabbroni ◽

Giovanni Fucà ◽

Francesca Ligorio ◽

Elena Fumagalli ◽

Marta Barisella ◽

...

Keyword(s):

Clinical Outcomes ◽

Proportional Hazards ◽

Case Series ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Low Grade ◽

High Grade ◽

Retrospective Case ◽

Well Differentiated ◽

The Impact

Background. We previously showed that grading can prognosticate the outcome of retroperitoneal liposarcoma (LPS). In the present study, we aimed to explore the impact of pathological stratification using grading on the clinical outcomes of patients with advanced well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) treated with trabectedin. Patients: We included patients with advanced WDLPS and DDLPS treated with trabectedin at the Fondazione IRCCS Istituto Nazionale dei Tumori between April 2003 and November 2019. Tumors were categorized in WDLPS, low-grade DDLPS, and high-grade DDLPS according to the 2020 WHO classification. Patients were divided in two cohorts: Low-grade (WDLPS/low-grade DDLPS) and high-grade (high-grade DDLPS). Results: A total of 49 patients were included: 17 (35%) in the low-grade cohort and 32 (65%) in the high-grade cohort. Response rate was 47% in the low-grade cohort versus 9.4% in the high-grade cohort (logistic regression p = 0.006). Median progression-free survival (PFS) was 13.7 months in the low-grade cohort and 3.2 months in the high-grade cohort. Grading was confirmed as an independent predictor of PFS in the Cox proportional-hazards regression multivariable model (adjusted hazard ratio low-grade vs. high-grade: 0.45, 95% confidence interval: 0.22–0.94; adjusted p = 0.035). Conclusions: In this retrospective case series, sensitivity to trabectedin was higher in WDLPS/low-grade DDLPS than in high-grade DDLPS. If confirmed in larger series, grading could represent an effective tool to personalize the treatment with trabectedin in patients with advanced LPS.

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Differential response rates in early-phase cancer clinical trials (EPCCT).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.3133 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 3133-3133

Author(s):

Rozana Abdul Rahman ◽

Neethu Billy Graham Mariam ◽

Hitesh Mistry ◽

Sreeja Aruketty ◽

Matt Church ◽

...

Keyword(s):

Proportional Hazards ◽

Performance Status ◽

Objective Response ◽

Progression Free Survival ◽

Response Rates ◽

Primary Objective ◽

Cox Proportional Hazards ◽

Sustained Response ◽

Phase Ii Trials ◽

Significant Difference

3133 Background: The primary objective of EPCCT (phase I and non-randomised phase II trials) is to determine the safety and tolerability of new therapeutic agents. Response rates (RR) in these trials have typically been reported at around 10-15%. Increasingly RR and survival outcomes are now investigated in EPCCT as primary or secondary objectives. Methods: Retrospective data analysis was performed on patients (pts) enrolled onto an EPCCT between January 2018 and December 2019 at The Christie NHS Foundation Trust, UK. Data on demographics, prior systemic treatment, sites of disease, performance status, comorbidities, types of therapy, RR, progression free survival (PFS), and overall survival (OS) were collected. Statistical analyses were performed with univariable and multivariable models. Objective response rate (ORR) was defined as the proportion of pts with complete response (CR) and partial response (PR). Duration of response (DOR) was from initial response to progressive disease (PD). Disease control rate (DCR) was defined as CR+PR+ stable disease (SD). Results: A total of 247 pts were treated across 46 EPCCTs. Median age 61 years; 57% female. Sixty-six percent of pts had ≥2 lines of treatment and the majority were ECOG PS 0/1 (98%). Eighty-one percent of pts had ≥2 sites of metastatic disease, and 13 major tumour types were included. Monotherapy trials (159 pts) were predominantly targeted therapies (TT; 60%), or immunotherapies (IO; 20%). Combination therapy trials (88 pts) were TT-based (68%) or IO-based (32%). Data for RR analyses was available for 231 pts. ORR across all trials was 15% (CR 2%) and DCR was 63%. The median DOR was 8.3 months (mos) (95% CI: 7.0 – 9.7) with 28% of pts responding for >6 mos and 7% for >12 mos. ORR in pooled IO treated pts was 27%, DCR was 65% with sustained response >6 mos seen in 37% of these pts. ORR in pooled TT treated pts was 9.4%, DCR was 60% and sustained response > 6 mos seen in 25% of pts. ORR for IO v TT treated pts was significantly different, p=0.007 (pearson chi square), but no significant difference was seen for DCR. Median PFS for all patients was 5.0 mos (95% CI: 4.1 – 6.0) and OS was 10.4 mos (95% CI: 8.4 – 13.0). OS for those with a PR is not reached (HR for PR v PD, 0.006 (95% CI: 0.002 – 0.18). Pts with SD appear to have significantly better OS compared to those with PD (14.6 v 4.2 mos, HR 0.2 (95% CI: 0.1 – 0.3). Multivariable Cox proportional hazards analysis for OS was significant for male gender (HR 1.9, p=0.002), presence of liver metastasis (HR 2.0, p=0.001), low Hb (HR 0.8, p=0.03) and log (LDH) (HR 1.9, p<0.001). Conclusions: Two-thirds of pts enrolled on EPCCTs benefitted in terms of DCR with significant OS improvement in those with PR and SD. Higher ORR were seen in pts receiving IO-based treatments however DCR was similar in IO and TT pts. Gender, presence of liver metastases, Hb count and LDH level contributed significantly to survival differences.

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Treatment Outcomes and Relative Dose Intensity of Chemotherapy in Slovene Patients With Advanced Hodgkin Lymphoma

10.21203/rs.3.rs-1209902/v1 ◽

2022 ◽

Author(s):

Samo Rozman ◽

Nina Ružić Gorenjec ◽

Barbara Jezeršek Novaković

Keyword(s):

Hodgkin Lymphoma ◽

Proportional Hazards ◽

Stage Iv ◽

Dose Intensity ◽

Progression Free Survival ◽

Cox Proportional Hazards ◽

Relative Dose Intensity ◽

Cox Proportional Hazards Models ◽

Stage Disease ◽

Stage Iv Disease

Abstract This retrospective study was undertaken to investigate the association of relative dose intensity (RDI) with the outcome of Hodgkin lymphoma (HL) patients with advanced stage disease receiving ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) and escalated BEACOPP regimen (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone). A total of 114 HL patients treated between 2004 and 2013 were enrolled for evaluation. RDI calculations were based on a Hryniuk's model. The association of variables with overall survival (OS) and progression-free survival (PFS) was analysed using univariate and multivariate Cox proportional hazards models. The median age of patients was 39 years, majority of patients were males and had stage IV disease. Fifty-four patients received ABVD and 60 received BEACOPP chemotherapy with 24 and 4 deaths, respectively. Patients in BEACOPP group were significantly younger with lower Charlson comorbidity index (CCI) in comparison with ABVD group, making the comparison of groups impossible. In ABVD group, RDI was not significantly associated with OS (p=0.590) or PFS (p=0.354) in a multivariate model where age was controlled. The low number of events prevented the analysis in the BEACOPP group. Patients' age was strongly associated with both OS and PFS: all statistically significant predictors for OS and PFS from univariate analyses (chemotherapy regimen, CCI, RDI) lost its effect in multivariate analyses where age was controlled. Based on our observations, we can conclude that RDI is not associated with the OS or PFS after the age is controlled, neither in all patients combined nor in individual chemotherapy groups.

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The association between triglyceride-glucose index, cardio-cerebrovascular diseases, and death in Korean adults: A retrospective study based on the NHIS-HEALS cohort

PLoS ONE ◽

10.1371/journal.pone.0259212 ◽

2021 ◽

Vol 16 (11) ◽

pp. e0259212

Author(s):

Joungyoun Kim ◽

Sang-Jun Shin ◽

Hee-Taik Kang

Keyword(s):

Retrospective Study ◽

Proportional Hazards ◽

Smoking Status ◽

Economic Status ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Cerebrovascular Diseases ◽

Cox Proportional Hazards ◽

Tyg Index ◽

All Cause Mortality

Background The triglyceride-glucose (TyG) index is a reliable indicator of insulin resistance. We aimed to investigate the TyG index in relation to cardio-cerebrovascular diseases (CCVDs and mortality. Methods This retrospective study included 114,603 subjects. The TyG index was categorized into four quartiles by sex: Q1, <8.249 and <8.063; Q2, 8.249‒<8.614 and 8.063‒<8.403; Q3, 8.614‒< 8.998 and 8.403‒<8.752; and Q4, ≥8.998 and ≥8.752, in men and women, respectively. To calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the primary outcomes (CCVDs and all-cause mortality) and secondary outcomes (cardiovascular diseases [CVDs], cerebrovascular diseases [CbVDs], CCVD-related deaths, or all-cause deaths), Cox proportional hazards regression models were adopted. Results Compared to Q1, the HRs (95% CIs) for the primary outcomes of Q2, Q3, and Q4 were 1.062 (0.981‒1.150), 1.110 (1.024−1.204), and 1.151 (1.058−1.252) in men and 1.099 (0.986−1.226), 1.046 (0.938−1.166), and 1.063 (0.954−1.184) in women, respectively, after adjusted for age, smoking status, drinking status, physical activity, body mass index, systolic blood pressure, low-density lipoprotein cholesterol, economic status, and anti-hypertensive medications. Fully adjusted HRs (95% CIs) for CVDs of Q2, Q3, and Q4 were 1.114 (0.969−1.282), 1.185 (1.031−1.363), and 1.232 (1.068−1.422) in men and 1.238 (1.017−1.508), 1.183 (0.971−1.440), and 1.238 (1.018−1.505) in women, respectively. The adjusted HRs (95% CIs) for ischemic CbVDs of Q2, Q3, and Q4 were 1.005 (0.850−1.187), 1.225 (1.041−1.441), and 1.232 (1.039−1.460) in men and 1.040 (0.821−1.316), 1.226 (0.981−1.532), and 1.312 (1.054−1.634) in women, respectively, while the TyG index was negatively associated with hemorrhagic CbVDs in women but not in men. The TyG index was not significantly associated with CCVD-related death or all-cause death in either sex. Conclusions Elevated TyG index was positively associated with the primary outcomes (CCVDs and all-cause mortality) in men and predicted higher risk of CVDs and ischemic CbVDs in both sexes.

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Abstract 19119: Concomitant Use of Antiplatelet Therapy with Edoxaban or Warfarin in Patients with Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial

Circulation ◽

10.1161/circ.130.suppl_2.19119 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Haiyan Xu ◽

Christian T Ruff ◽

Robert P Giugliano ◽

Sabina A Murphy ◽

Indravadan Patel ◽

...

Keyword(s):

Atrial Fibrillation ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Drug Exposure ◽

Proportional Hazards ◽

Absolute Risk ◽

Cox Proportional Hazards ◽

Relative Efficacy ◽

Double Blind ◽

Risk Of Bleeding

BACKGROUND: Patients with atrial fibrillation (AF) who receive both antiplatelet (AP) and anticoagulant therapy are at markedly higher risk of bleeding. The ENGAGE AF-TIMI 48 trial showed that both the high- (HD) and low-dose (LD) regimens of the once-daily factor Xa inhibitor edoxaban (Edox) were as effective as well-managed warfarin (Warf) (median TTR 68.4%) in preventing stroke or systemic embolism (SEE) with significant reductions in major bleeding and cardiovascular mortality. In this study, we assessed the relative efficacy and safety of Edox as compared with Warf in patients with and without concomitant use of AP therapy. METHODS: This was a randomized, double-blind, double-dummy trial comparing HD (60 mg daily, reduced to 30mg in patients with anticipated increased drug exposure) and LD (30 mg daily, reduced to 15mg) Edox with Warf. Dual AP therapy was prohibited while receiving study drug. Cox proportional hazards models were performed stratified by AP use at 3 months with treatment as a covariate. RESULTS: Of the 21,105 patients, 4,912 (23%) were receiving AP therapy at 3 months (92% aspirin). Patients who received concomitant AP therapy had higher rates of major bleeding compared to patients who did not (Fig). Both Edox regimens had similar relative efficacy in preventing stroke or SEE compared with Warf regardless of concomitant AP use (P int >0.10 for both) with consistent reductions in major bleeding (HD Edox vs. Warf: P int =0.91; LD Edox vs. Warf: P int =0.59). In patients randomized to LD Edox, AP therapy was associated with a further reduction in the net clinical outcome of death, stroke, SEE, or major bleeding (P int =0.02) compared with Warf. CONCLUSIONS: Regardless of concomitant AP therapy, both doses of Edox significantly reduced bleeding compared to well-managed Warf. The safety profile of Edox may be particularly attractive in patients with AF who receive a combination of AP and anticoagulant therapy because of higher absolute risk of bleeding.

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