Abstract 159: Evaluation of Clinical Outcomes among Nonvalvular Atrial Fibrillation Patients Treated With Warfarin or Rivaroxaban Stratified by Presence or Absence of CKD in a Claims Database

2017 ◽  
Vol 10 (suppl_3) ◽  
Author(s):  
Matthew R Weir ◽  
Lloyd Haskell ◽  
Jeffrey S Berger ◽  
Veronica Ashton ◽  
François Laliberté ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Major Bleeding ◽  
Bleeding Event ◽  
Data Availability ◽  
Thromboembolic Events ◽  
Bleeding Events ◽  
Nonvalvular Atrial Fibrillation ◽  
Claims Database ◽  
Increased Risk

Introduction: Renal functional impairment is linked to an increased risk of thromboembolic and bleeding events in patients with nonvalvular atrial fibrillation (NVAF) treated with warfarin and rivaroxaban. Anticoagulants such as warfarin and rivaroxaban are often recommended to reduce the risk of stroke in NVAF patients. The purpose of this study was to evaluate and compare thromboembolic and bleeding event rates for warfarin and rivaroxaban patients stratified by presence of chronic kidney disease (CKD). Methods: Claims from the IMS Health Real-World Data Adjudicated Claims database from 05/2011-6/2015 were analyzed. Adult patients with NVAF who had ≥6 months of baseline data prior to the first dispensing of warfarin or rivaroxaban after 11/2011 were included. Patients were followed until the end of index therapy or end of data availability/insurance coverage. Outcomes were stratified by presence of CKD for ischemic stroke, major bleeding, and a composite measure of thromboembolic events (ischemic stroke, myocardial infarction (MI) or venous thromboembolism (VTE)) and analyzed using hazard ratios (HRs). Adjustments for confounding were made with inverse probability of treatment weights (IPTW). Results: The analysis included 39,872 rivaroxaban (9.0% [3,572 of 39,872] with CKD) and 48,637 warfarin patients (16.9% [8,230 of 48,637] with CKD). As expected, thromboembolic and bleeding events were more common in patients with CKD than those without CKD. Rivaroxaban patients had significantly lower risk of ischemic stroke, both in the overall population (HR = 0.79 [0.68-0.90], p=0.0008) and for those with CKD (HR = 0.55 [0.40-0.77], p=0.0004). A composite of thromboembolic events were lower with rivaroxaban irrespective of CKD. Major bleeding rates were comparable across all groups. Table 1 reports incidence rates and HRs stratified by presence of CKD. Conclusions: This study suggests that, in an adult population with NVAF, rivaroxaban-treated patients had fewer ischemic strokes across all patients, including patients with renal impairment. Rivaroxaban-treated patients also had significantly better outcomes for the composite (VTE, MI, or stroke) measure across all groups. Bleeding rates were comparable across all groups.

scholarly journals Patient characteristics and stroke and bleeding events in nonvalvular atrial fibrillation patients treated with apixaban and vitamin K antagonists: a Spanish real-world study

2019 ◽  
Vol 8 (14) ◽  
pp. 1201-1212 ◽  
Author(s):  
Sreeram V Ramagopalan ◽  
Antoni Sicras-Mainar ◽  
Carlos Polanco-Sanchez ◽  
Robert Carroll ◽  
Jaime F de Bobadilla
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Medical Records ◽  
Vitamin K Antagonists ◽  
Patient Characteristics ◽  
Minor Bleeding ◽  
Thromboembolic Events ◽  
Systemic Embolism ◽  
Bleeding Events ◽  
Nonvalvular Atrial Fibrillation

Aim: To compare the risk of stroke, systemic thromboembolism and bleeding, in patients initiating apixaban or acenocoumarol for the treatment of nonvalvular atrial fibrillation. Methods: An observational, retrospective study was performed using medical records of patients who initiated apixaban or acenocoumarol between 2015 and 2017. Propensity score matching was used to match patients; stroke, systemic thromboembolism, major and minor bleeding events were compared between the matched patients. Results: Patients who were prescribed apixaban had a lower rate of systemic embolism/stroke (hazard ratio [HR] = 0.54; 95% CI: 0.38–0.78; p = 0.001), minor bleeding (HR = 0.64; 95% CI: 0.52–0.79; p < 0.001) and major bleeding (HR = 0.51; 95% CI: 0.37–0.72; p < 0.001). Conclusion: Patients prescribed apixaban for the treatment of nonvalvular atrial fibrillation had lower rates of thromboembolic events and minor/major bleeding than patients on acenocoumarol.

scholarly journals Long-Term Costs of Ischemic Stroke and Major Bleeding Events among Medicare Patients with Nonvalvular Atrial Fibrillation

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Catherine J. Mercaldi ◽  
Kimberly Siu ◽  
Stephen D. Sander ◽  
David R. Walker ◽  
You Wu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Major Bleeding ◽  
First Year ◽  
Bleeding Events ◽  
Nonvalvular Atrial Fibrillation ◽  
Treatment Regimens ◽  
First Occurrence ◽  
The Difference

Purpose. Acute healthcare utilization of stroke and bleeding has been previously examined among patients with nonvalvular atrial fibrillation (NVAF). The long-term cost of such outcomes over several years is not well understood.Methods. Using 1999–2009 Medicare medical and enrollment data, we identified incident NVAF patients without history of stroke or bleeding. Patients were followed from the first occurrence of ischemic stroke, major bleeding, or intracranial hemorrhage (ICH) resulting in hospitalization. Those with events were matched with 1–5 NVAF patients without events. Total incremental costs of events were calculated as the difference between costs for patients with events and matched controls for up to 3 years.Results. Among the 25,465 patients who experienced events, 94.5% were successfully matched. In the first year after event, average incremental costs were $32,900 for ischemic stroke, $23,414 for major bleeding, and $47,640 for ICH. At 3 years after these events, costs remained elevated by $3,156–$5,400 per annum.Conclusion. While the costs of stroke and bleeding among patients with NVAF are most dramatic in the first year, utilization remained elevated at 3 years. Cost consequences extend beyond the initial year after these events and should be accounted for when assessing the cost-effectiveness of treatment regimens for stroke prevention.

scholarly journals Burden of major gastrointestinal bleeding among oral anticoagulant-treated non-valvular atrial fibrillation patients

2021 ◽  
Vol 14 ◽  
pp. 175628482199735
Author(s):  
Steven Deitelzweig ◽  
Allison Keshishian ◽  
Amiee Kang ◽  
Amol D. Dhamane ◽  
Xuemei Luo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Oral Anticoagulant ◽  
Proportional Hazards ◽  
Bleeding Event ◽  
Cox Proportional Hazards ◽  
High Rate ◽  
Gi Bleeding ◽  
Increased Risk ◽  
Gi Bleed

Background: Gastrointestinal (GI) bleeding is the most common type of major bleeding associated with oral anticoagulant (OAC) treatment. Patients with major bleeding are at an increased risk of a stroke if an OAC is not reinitiated. Methods: Non-valvular atrial fibrillation (NVAF) patients initiating OACs were identified from the Centers for Medicare and Medicaid Services ( CMS) Medicare data and four US commercial claims databases. Patients who had a major GI bleeding event (hospitalization with primary diagnosis of GI bleeding) while on an OAC were selected. A control cohort of patients without a major GI bleed during OAC treatment was matched to major GI bleeding patients using propensity scores. Stroke/systemic embolism (SE), major bleeding, and mortality (in the CMS population) were examined using Cox proportional hazards models with robust sandwich estimates. Results: A total of 15,888 patients with major GI bleeding and 833,052 patients without major GI bleeding were included in the study. Within 90 days of the major GI bleed, 58% of patients discontinued the initial OAC treatment. Patients with a major GI bleed had a higher risk of stroke/SE [hazard ratio (HR): 1.57, 95% confidence interval (CI): 1.42–1.74], major bleeding (HR: 2.79, 95% CI: 2.64–2.95), and all-cause mortality (HR: 1.29, 95% CI: 1.23–1.36) than patients without a major GI bleed. Conclusion: Patients with a major GI bleed on OAC had a high rate of OAC discontinuation and significantly higher risk of stroke/SE, major bleeding, and mortality after hospital discharge than those without. Effective management strategies are needed for patients with risk factors for major GI bleeding.

A Systematic Review of Anticoagulation Strategies for Patients With Atrial Fibrillation in Critical Care.

2021 ◽  
Author(s):  
Alexandra Jayne Nelson ◽  
Brian W Johnston ◽  
Alicia Achiaa Charlotte Waite ◽  
Gedeon Lemma ◽  
Ingeborg Dorothea Welters
Keyword(s):  
Atrial Fibrillation ◽  
Critical Care ◽  
Critically Ill ◽  
Major Bleeding ◽  
Critically Ill Patients ◽  
Thromboembolic Events ◽  
Bleeding Events ◽  
Major Bleeding Events ◽  
The Impact ◽  
Anticoagulated Patients

Background. Atrial fibrillation (AF) is the most common cardiac arrhythmia in critically ill patients. There is a paucity of data assessing the impact of anticoagulation strategies on clinical outcomes for general critical care patients with AF. Our aim was to assess the existing literature to evaluate the effectiveness of anticoagulation strategies used in critical care for AF. Methodology. A systematic literature search was conducted using MEDLINE, EMBASE, CENTRAL and PubMed databases. Studies reporting anticoagulation strategies for AF in adults admitted to a general critical care setting were assessed for inclusion. Results. Four studies were selected for data extraction. A total of 44087 patients were identified with AF, of which 17.8-49.4% received anticoagulation. The reported incidence of thromboembolic events was 0-1.4% for anticoagulated patients, and 0-1.3% in non-anticoagulated patients. Major bleeding events were reported in three studies and occurred in 7.2-8.6% of the anticoagulated patients and up to 7.1% of the non-anticoagulated patients. Conclusions. There was an increased incidence of major bleeding events in anticoagulated patients with AF in critical care compared to non-anticoagulated patients. There was no significant difference in the incidence of reported thromboembolic events within studies, between patients who did and did not receive anticoagulation. However, the outcomes reported within studies were not standardised, therefore, the generalisability of our results to the general critical care population remains unclear. Further data is required to facilitate an evidence-based assessment of the risks and benefits of anticoagulation for critically ill patients with AF.

scholarly journals Analysis of Influencing Factors of Compliance with Non-Vitamin K Antagonist Oral Anticoagulant in Patients with Nonvalvular Atrial Fibrillation and Correlation with the Severity of Ischemic Stroke

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Li Zhu ◽  
Xiaodan Zhang ◽  
Jing Yang
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Influencing Factors ◽  
Clinical Supervision ◽  
Vitamin K ◽  
Pearson Correlation ◽  
Anticoagulation Therapy ◽  
Vitamin K Antagonist ◽  
Nonvalvular Atrial Fibrillation ◽  
Increased Risk

Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of stroke and thrombus, and anticoagulant therapy is a key link in the prevention of stroke. At present, the anticoagulation rate of atrial fibrillation in China is low, and there are many factors affecting the adherence of patients with atrial fibrillation to anticoagulation. Non-vitamin K antagonist oral anticoagulants (NOACs) are anticoagulant with high application value due to their high safety and low risk of intracranial hemorrhage, stroke, and death. However, the compliance of NOACs is poor, and the current situation of anticoagulants in China is not optimistic. In this study, a total of 156 patients with NVAF who received NOAC anticoagulation therapy in our hospital from January 2018 to January 2019 were retrospectively analyzed. The results showed that education background, place of residence, number of complications, CHA2DS2-VASc score, and HAS-BLED score were independent influencing factors for NOACS compliance of NVAF patients. Also, the Pearson correlation analysis showed that there was a negative correlation (r = −0.465, P < 0.001 ) between NOAC compliance and severity of ischemic stroke in patients with NVAF. Therefore, clinical supervision and management of patients with NVAF after NOACs should be strengthened to improve the compliance of patients with NVAF after NOACs, reduce the damage of ischemic stroke, and improve their prognosis.

Long-term clinical outcomes after major bleeding in patients with atrial fibrillation: the Fushimi AF registry

2020 ◽  
Author(s):  
Hisashi Ogawa ◽  
Yoshimori An ◽  
Kenjiro Ishigami ◽  
Syuhei Ikeda ◽  
Kosuke Doi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischaemic Stroke ◽  
Clinical Outcomes ◽  
Major Bleeding ◽  
Bleeding Event ◽  
Community Based ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Aims Oral anticoagulants reduce the risk of ischaemic stroke but may increase the risk of major bleeding in atrial fibrillation (AF) patients. Little is known about the clinical outcomes of patients after a major bleeding event. This study assessed the outcomes of AF patients after major bleeding. Methods and results The Fushimi AF Registry is a community-based prospective survey of the AF patients in Fushimi-ku, Kyoto, Japan. Analyses were performed on 4304 AF patients registered by 81 institutions participating in the Fushimi AF Registry. We investigated the demographics and outcomes of AF patients who experienced major bleeding during follow-up period. During the median follow-up of 1307 days, major bleeding occurred in 297 patients (6.9%). Patients with major bleeding were older than those without (75.6 vs. 73.4 years; P &lt; 0.01). They were more likely to have pre-existing heart failure (33.7% vs. 26.7%; P &lt; 0.01), history of major bleeding (7.7% vs. 4.0%; P &lt; 0.01), and higher mean HAS-BLED score (2.05 vs.1.73; P &lt; 0.01). On landmark analysis, ischaemic stroke or systemic embolism occurred in 17 patients (3.6/100 person-years) after major bleeding and 227 patients (1.7/100 person-years) without major bleeding, with an adjusted hazard ratio (HR) of 1.93 [95% confidence interval (CI), 1.06–3.23; P = 0.03]. All-cause mortality occurred in 97 patients with major bleeding (20.0/100 person-years) and 709 (5.1/100 person-years) patients without major bleeding [HR 2.73 (95% CI, 2.16–3.41; P &lt; 0.01)]. Conclusion In this community-based cohort, major bleeding is associated with increased risk of subsequent all-cause mortality and thromboembolism in the long-term amongst AF patients. Trial registration https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000005834. (last accessed 22 October 2020)

P3758Clinical characteristics and outcomes of atrial fibrillation patients with thrombocytopenia: the Fushimi AF Registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Ishigami ◽  
Y Aono ◽  
S Ikeda ◽  
K Doi ◽  
Y An ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Platelet Count ◽  
Major Bleeding ◽  
Bleeding Event ◽  
Bleeding Events ◽  
Major Bleeding Event ◽  
Entire Cohort ◽  
Severe Group ◽  
The Mean

Abstract Background Thrombocytopenia is sometimes found in routine blood tests and is reported as a risk factor of major bleeding events and incidence of all-cause death after percutaneous coronary intervention. However, the influence of thrombocytopenia on clinical outcomes in patients with atrial fibrillation (AF) remains unknown. Purpose We aimed to investigate relationship between baseline platelet count and clinical outcomes such as all-cause death, hospitalization for heart failure, and the major bleeding event in AF patients. Methods The Fushimi AF Registry was designed to enroll all of the AF patients in Fushimi-ku, Kyoto. Fushimi-ku is densely populated with a total population of 283,000 and is assumed to represent a typical urban community in Japan. Follow-up data with baseline platelet counts were available in 4,179 patients from March 2011 to November 2018. We divided the entire cohort into 3 groups according to baseline platelet level: No thrombocytopenia (≥150,000/μL, n=3,323), Mild thrombocytopenia (100,000–149,999/μL, n=707), and Moderate/severe thrombocytopenia (≤99,999/μL, n=149). Results In the entire cohort, the mean age was 73 years, 40% were women, and the mean body weight and body mass index was 59 kg and 23.1 kg/m2, and the median platelet count were 192,000/μL (interquartile range 156,000 to 232,000/μL), respectively. Compared to No thrombocytopenia, patients with thrombocytopenia were older (No vs. Mild vs. Moderate/severe; 73.3 years vs. 76.5 years vs. 75.8 years, p<0.0001), more likely to have heart failure (27.0% vs. 32.8% vs. 41.6%, p<0.0001), more likely to have chronic renal disease (35.7% vs. 42.6% vs. 57.7%, p<0.0001), and had higher CHADS2 score (2.05 vs. 2.17 vs. 2.34, p=0.0039) and CHA2DS2-VASc score (3.40 vs. 3.52 vs. 3.71, p=0.0416). Patients with thrombocytopenia had lower hemoglobin (13.0 vs. 12.8 vs. 11.6, p<0.0001) than No thrombocytopenia. However, prevalence of previous major bleeding events was comparable between three groups (4.66% vs. 4.67% vs. 5.37%, p=0.92) On Kaplan-Meier analysis, the incidence of all-cause death was higher in Mild group (hazard ratio [HR] 1.51; 95% confidence interval [CI] 1.28–1.77) and Moderate/severe group (HR 2.97; 95% CI 2.28–3.80) than No group (Figure 1). The incidence of hospitalization for heart failure was higher in Mild group (HR 1.62; 95% CI 1.31–1.99) and Moderate/severe group (HR 2.64; 95% CI 1.76–3.81) than No group (Figure 2). The incidence of major bleeding event was higher in Mild group (HR 1.46; 95% CI 1.11–1.91) and Moderate/severe group (HR 2.45; 95% CI 1.41–3.91) than No group (Figure 3). Conclusion Thrombocytopenia in AF patients was associated with higher incidence of all-cause death, hospitalization for heart failure, and major bleeding event in the Fushimi AF Registry. Acknowledgement/Funding Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, Bayer Healthcare,and Daiichi-Sankyo

scholarly journals Low Body Weight Increases the Risk of Ischemic Stroke and Major Bleeding in Atrial Fibrillation: The COOL-AF Registry

2020 ◽  
Vol 9 (9) ◽  
pp. 2713
Author(s):  
Rungroj Krittayaphong ◽  
Ply Chichareon ◽  
Chulalak Komoltri ◽  
Sakaorat Kornbongkotmas ◽  
Ahthit Yindeengam ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Weight ◽  
Ischemic Stroke ◽  
Major Bleeding ◽  
Demographic Data ◽  
Adverse Outcomes ◽  
Multicenter Cohort Study ◽  
Clinical Events ◽  
Increased Risk

We aimed to determine if low body weight (LBW) status (<50 kg) is independently associated with increased risk of ischemic stroke and bleeding in Thai patients with non-valvular atrial fibrillation (NVAF). (1) Background: It has been unclear whether LBW influence clinical outcome of patients with NVAF. (2) Methods: This prospective multicenter cohort study included patients enrolled in the COOL-AF Registry. The following data were collected: demographic data, medical history, risk factors and comorbid conditions, laboratory and investigation data, and medications. Follow-up data were collected every 6 months. Clinical events during follow-up were confirmed by the adjudication committee. (3) Results: A total of 3367 patients were enrolled. The mean age was 67.2 ± 11.2 years. LBW was present in 338 patients (11.3%). Anticoagulant and antiplatelet was prescribed in 75.3% and 26.2% of patients, respectively. Ischemic stroke, major bleeding, intracerebral hemorrhage (ICH), and death occurred during follow-up in 2.9%, 4.4%, 1.4%, and 7.7% of patients, respectively, during 25.7 months follow-up. LBW was an independent predictor of ischemic stroke, major bleeding, ICH, and death, with a hazard ratio of 2.40, 1.79, 2.37, and 2.65, respectively. (4) Conclusions: LBW was independently associated with increased risk of adverse outcomes in Thai patients with NVAF. This should be carefully considered when balancing the risks and benefits of stroke prevention among patients with different body weights.

Risk Factors for Bleeding in Patients with Nonvalvular Atrial Fibrillation Who Are Receiving Anticoagulant Therapy with Ximelagatran or Warfarin: Findings from the SPORTIF III and V Trials.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 528-528
Author(s):  
James D. Douketis ◽  
Karin Arneklev ◽  
Samuel Goldhaber ◽  
John Spandorfer ◽  
Frank Halperin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Patient Population ◽  
Left Ventricular ◽  
Nonvalvular Atrial Fibrillation ◽  
Increased Risk ◽  
Risk For Bleeding ◽  
Statin Use

Abstract Background: Ximelagatran is a novel oral direct thrombin inhibitor that is as effective as warfarin in preventing stroke and other thromboembolic complications in patients with nonvalvular atrial fibrillation (AF). Risk factors for bleeding with warfarin are known, but risk factors for bleeding with ximelagatran have not been described. Unlike warfarin, ximelagatran has a predictable anticoagulant effect, does not require anticoagulation monitoring, has a low potential for interactions with drugs, food, or alcohol, and is not affected by genetic polymorphisms. We undertook an exploratory analysis of a large patient database to identify conventional and novel risk factors for bleeding in ximelagatran-treated patients, in warfarin-treated patients, and in all patients, irrespective of treatment. Methods: We undertook a pooled analysis of the SPORTIF III and V trials trials, which included 7329 patients with nonvalvular AF who received oral ximelagatran, 36 mg twice daily, or warfarin, administered to achieve a target international normalized ratio of 2.0–3.0. Patients had nonvalvular AF and 1 or more risk factors for stroke: hypertension; age ≥75 years; previous stroke, transient ischemic attack (TIA) or systemic embolism; left ventricular dysfunction; age ≥65 years and coronary artery disease; or age ≥65 years and diabetes mellitus. Major exclusion criteria were: mitral stenosis; previous heart valve surgery; transient AF; increased risk for bleeding. Multivariate logistic regression analysis was used to identify independent risk factors for major bleeding. The hazard ratio (HR) for major bleeding, and corresponding 95% confidence interval (CI), was calculated for each variable in the regression model. Results: The Table presents risk factors in which there was a significant or a non-significant (NS) association with major bleeding in ximelagatran-treated or warfarin-treated patients, and in the combined patient population. Risk factor Ximelagatran-treated patients, HR (95% CI) Warfarin-treated patients, HR (95% CI) Combined patient population, HR (95% CI) Aspirin use 1.65 (1.07, 2.55) 2.40 (1.69, 3.42) 1.96 (1.49, 2.58) Increasing age 1.03 (1.01, 1.05) 1.06 (1.03, 1.08) 1.04 (1.03, 1.06) Prior liver disease NS 4.96 (1.57, 15.62) NS Prior stroke or TIA 1.78 (1.16, 2.73) NS NS Diabetes mellitus 1.80 (1.18, 2.75) NS 1.39 (1.05, 1.86) Asian race NS NS 1.99 (1.16, 3.42) Statin use 0.62 (0.39, 0.97) 0.61 (0.42, 0.88) 0.62 (0.39, 0.97) Conclusions: Overall, the bleeding risk was lower with ximelagatran compared with warfarin. Aspirin use and increasing age were associated with an increased risk of bleeding in both ximelagatran- and warfarin-treated patients. Statin use was associated with a decreased risk for bleeding in both groups.

A phase I feasability study of concurrent fondaparinux (F) with carboplatin (Crb) and paclitaxel (P) for metastatic non-small cell lung cancer (NSCLC): An analysis of coagulation/angiogenic biomarker (CABM) kinetics.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19143-e19143
Author(s):  
David James Mooney ◽  
Debi Miley ◽  
Mary Jerome ◽  
Stefan C. Grant ◽  
Francisco Robert
Keyword(s):  
Major Bleeding ◽  
Metastatic Cancer ◽  
Bleeding Event ◽  
Stage Iv ◽  
Endothelial Damage ◽  
Minor Bleeding ◽  
Bleeding Events ◽  
Thrombotic Risk ◽  
Increased Risk ◽  
Angiogenic Biomarkers

e19143 Background: There is an association between risk of thrombosis and metastatic cancer. Chemotherapy (C) also independently increases thrombotic risk. This increased risk is multifactorial, including endothelial damage and release of angiogenic cytokines. We hypothesized that adding anticoagulation to C may decrease thrombotic risk and also, potentially, have anti-tumor effect. Methods: The primary aim of this study was to determine the tolerability and safety (bleeding events) of the combination of F with 21-day cycle chemotherapy (Crb AUC 6 + P 200 mg/m2) in two cohorts of untreated patients (pts) with stage IV NSCLC. The secondary objectives were to determine incidence of venous thrombosis (VT), changes in CABM parameters during treatment, and clinical efficacy endpoints. Two cohorts of pts received F from cycles 2-4 with Crb+P. Cohort A received 2.5 mg F daily from cycle 2-4. Cohort B received 7.5 mg of F on day 1, 2 of cycle 2-4 and 2.5 mg F on day 3-21. Results: Clinical data from 19 evaluable pts are as follows: median age 55 years, 63% male, and 32% adenocarcinoma. There was no major bleeding event (BE) in either cohort, and 5 pts had a minor BE. There was no VT. Median time to progression was 5 months (3.8-6.2 months), and overall survival was 10 months (4.3-15.6 months). Baseline values of sensitive markers of activated coagulation (D-Dimer, Thrombin Anti-Thrombin Complex) were above the normal range in most patients. These biomarkers tended to increase during the first cycle (without F); whereas the same markers decreased during the second cycle (with F). A reduction of the angiogenic biomarkers during therapy was observed with VEGF, TGF-β1, and Angiopoietin-1. Conclusions: Concurrent treatment with F and chemotherapy for metastatic NSCLC is feasible with no major bleeding and little minor bleeding. During chemotherapy, coagulant and angiogenic biomarkers tended to increase, perhaps suggesting an increase in thrombogenic state. When F was added, these markers trended downward, suggesting that the proangiogenic state associated with cancer may be significantly altered by anticoagulation. Clinical trial information: NCT00476216.

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