Do the Safety and Efficacy Outcomes Reported in the Clinical Trials of Direct Oral Anticoagulants (DOAC) Translate to the Real-World?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2335-2335
Author(s):  
Shammim Haji ◽  
Jignesh P Patel ◽  
Vivian Auyeung ◽  
Lara N Roberts ◽  
Julia Czuprynska ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Major Bleeding ◽  
Real World ◽  
Research Funding ◽  
Oral Anticoagulants ◽  
Phase Iii ◽  
World Population ◽  
Safety And Efficacy ◽  
The Real ◽  
Pooled Data

Abstract Do the safety and efficacy outcomes reported in the clinical trials of direct oral anticoagulants (DOAC) translate to the 'real-world'? Background: A number of DOACs are now available for clinicians to prescribe in clinical practice. Whilst the results from large clinical trials demonstrate that these agents are as effective as vitamin K antagonists, there is some concern that the patients studied in the trials were not representative of patients, clinicians encounter in everyday practice. The aim of our study was to compare the real-world clinic population commenced on a DOAC to that from the clinical trials for these agents, in order to assess potential differences in safety and efficacy. Patients and methods: A retrospective observational cohort study was undertaken. Patients who were initiated on a DOAC (apixaban, dabigatran and rivaroxaban) at a large teaching hospital in South East London between 1st August 2012 and 31st July 2014 were identified through pharmacy issue data with those followed-up for a minimum of 6 months included. Baseline demographic data, rates of stroke/VTE and rates of major/non-major clinically relevant (NMCR) (ISTH definition) bleeding were assessed and compared to pooled data reported from the corresponding Phase III trials. Differences between groups were compared using t-tests or chi-squared tests. Results: During the review period, 748 patients were initiated on a DOAC, 365 for atrial fibrillation (AF) and 383 for venous thromboembolism (VTE). In terms of demographic differences, the real-world AF population comprised more females, were significantly older, had poorer renal function and a lower body weight. In contrast, the real-world VTE population typically had a higher body weight and poorer renal function, compared to the trial population, (table 1). Efficacy of DOACs was found to be similar across both the VTE and AF populations. With respect to safety, the real-world AF population experienced similar rates of major bleeding and a significantly lower rate of NMCR bleeding compared to the trial populations. In contrast, the real-world VTE population experienced a significantly higher rate of major bleeding, particularly gastrointestinal bleeding. Although the rate of NMCR bleeding was similar, there was a significantly higher rate of urogenital bleeding in the real-world VTE population, specifically heavy menstrual bleeding in women. Conclusions: The efficacy outcomes of DOAC use in a real-world AF and VTE population are consistent with the Phase III trials, despite some significant differences in baseline characteristics. However, a significantly increased rate of major bleeding was observed in the real-world VTE population, which requires further investigation. Table 1. Baseline demographic characteristics, efficacy and safety outcomes in the real-world population versus the trial population Atrial Fibrillation Venous Thromboembolism Trial population+N=28,342 Real-world population Trial population++ Real-world population N=365 N=8,716 N=383 Baseline Demographics, mean (SD) unless otherwise specified Age, years 72 (9.6) 76.8 * (12.1) 56.9 (14.2) 55.6 (18.7) Female (%) 10451 (36.9) 215 * (58.9) 3753 (43.1) 184 (48.0) Weight, kg 82.7 (19.5) 77.3 * (22.6) 84.9 (19.6) 88.2 * (23.0) Creatinine clearance, mL/min 69 (26.7) 58.1 * (26.9) 105.8 (40.7) 91.1 * (37.6) Concomitant aspirin therapy 10341 (36.5) 49 * (13.4) - 0 (0) Previous VKA use (%) 15711 (55.4) 193 (52.9) - 85 (22.2) Efficacy (%) All-cause mortality 1695 (6.0) 37 * (9.1) 160 (1.8) 10 (2.5) Stroke 676 (2.4) 8 (2.0) - 1 (0.3) VTE 39 (0.1) 1 (0.2) 192 (2.2) 7 (1.8) Safety (%) Major Bleeding 1419 (5.0) 17 (4.2) 79 (0.9) 15 * (3.8) Intracranial 170 (0.6) 1 (0.2) 6 (0.1) 2 * (0.5) Gastrointestinal 644 (2.3) 8 (2.0) 8 (0.1) 8 * (2.0) Non-major Clinically relevant (NMCR) bleeding 4824 (17.0) 30 * (7.4) 540 (6.2) 26 (6.6) Gastrointestinal - 9 (2.2) 53 (4.2) 10 (2.5) Urogenital 296 (4.2) 16 (3.9) 100 (2.5) 38 * (9.6) +Pooled data from ARISTOTLE, RE-LY and ROCKET-AF trials ++Pooled data from AMPLIFY, RE-COVER and EINSTEIN-PE/DVT trials *p<0.05 Disclosures Patel: Bayer plc: Research Funding. Auyeung:Bayer PLC: Research Funding. Arya:Bayer plc: Research Funding.

Impact of weight on the efficacy and safety of direct-acting oral anticoagulants in patients with non-valvular atrial fibrillation: a meta-analysis

EP Europace ◽  
2020 ◽  
Vol 22 (3) ◽  
pp. 361-367 ◽  
Author(s):  
Aaqib H Malik ◽  
Srikanth Yandrapalli ◽  
Suchith Shetty ◽  
Wilbert S Aronow ◽  
Diwakar Jain ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Outcome Data ◽  
Phase Iii ◽  
Safety And Efficacy ◽  
Low Bmi ◽  
Direct Acting ◽  
The Impact ◽  
Direct Acting Oral Anticoagulants

Abstract Aims This study sought to determine the impact of weight and body mass index (BMI) on the safety and efficacy of direct-acting oral anticoagulants (DOACs) compared with warfarin in patients with non-valvular atrial fibrillation. Methods and results A systematic literature search was employed in PubMed, Embase, and Cochrane clinical trials with no language or date restrictions. Randomized trials or their substudies were assessed for relevant outcome data for efficacy that included stroke or systemic embolization (SSE), and safety including major bleeding and all-cause mortality. Binary outcome data and odds ratios from the relevant articles were used to calculate the pooled relative risk. For SSE, the data from the four Phase III trials showed that DOACs are better or similarly effective with low BMI 0.73 (0.56–0.97), normal BMI 0.72 (0.58–0.91), overweight 0.87 (0.76–0.99), and obese 0.87 (0.76–1.00). The risk of major bleeding was also better or similar with DOACs in all BMI subgroups with low BMI 0.62 (0.37–1.05), normal BMI 0.72 (0.58–0.90), overweight 0.83 (0.71–0.96), and obese 0.91 (0.81–1.03). There was no impact on mortality in all the subgroups. In a meta-regression analysis, the effect size advantage of DOACs compared with warfarin in terms of safety and efficacy gradually attenuated with increasing weight. Conclusion Our findings suggest that a weight-based dosage adjustment may be necessary to achieve optimal benefits of DOACs for thromboembolic prevention in these patients with non-valvular atrial fibrillation. Further dedicated trials are needed to confirm these findings. PROSPERO 2019 CRD42019140693. Available from: https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42019140693.

Survival among metastatic colorectal patients in clinical trials compared to the real world.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 673-673
Author(s):  
Ziwei Wang ◽  
Lindsay Hwang ◽  
James Don Murphy
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Metastatic Colorectal Cancer ◽  
Median Survival ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Phase Iii ◽  
The Real ◽  
Clinical Trial Results

673 Background: Randomized clinical trials play a central role in clinical research though only a small fraction of patients partake in clinical studies. Questions thus arise regarding the generalizability of clinical trial results to the remainder of the population. This study evaluated whether patient survival from randomized clinical trials in metastatic colorectal cancer reflects real world outcomes. Methods: A Pubmed search was used to identify randomized phase III clinical trials of first-line treatment for metastatic colorectal cancer published between 2005 and 2010. We excluded secondary or pooled analyses, second-line treatments, non-metastatic patients, non-English language, and non-randomized studies. Thirty-one clinical trials met these criteria, comprised of 79 distinct clinical trial arms. Overall survival among clinical trial patients was compared to metastatic colorectal cancer patients within the Surveillance, Epidemiology, and End Results (SEER) program. Within SEER, we restricted the analysis time-period and age of patients to match the enrollment period and age of patients within each individual clinical trial. Results: The clinical trials enrolled a total of 16,614 patients. Among all clinical trial arms the median survival ranged from 6.7-62 months, 1-year survival ranged from 30-97%, and 2-year survival ranged from 6-88%. Compared to SEER, the median survival was higher in 95% of the individual clinical trial arms by an average of 5.4 months (p<0.0001). The 1-year survival was higher in 94% of the clinical trial arms by an average of 16.7% (p<0.0001). The 2-year survival was higher in 71% of the clinical trial arms by an average of 7.2% (p<0.0001). Conclusions: This study found substantially improved survival among clinical trial participants compared to patients in the SEER database suggesting that survival estimates from clinical trials may not generalize to the “real world.” Potential patient factors such as differences in underlying comorbidity, performance status, disease burden, as well as variation in treatment could not be addressed in this study, though these factors likely explain some of the observed survival differences.

Abstract 18465: Real World Comparison of Major Bleeding Risk Among Non-valvular Atrial Fibrillation Patients Newly Initiated on Warfarin versus Apixaban 5mg BID, Dabigatran 150 mg BID, or Rivaroxaban 20 mg QD

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Shital Kamble ◽  
Xianying Pan ◽  
Hemant Phatak ◽  
Hugh Kawabata ◽  
Cristina Masseria ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Real World ◽  
Lower Risk ◽  
Proportional Hazards Model ◽  
Oral Anticoagulants ◽  
Bleeding Event ◽  
Cox Proportional Hazards Model ◽  
Charlson Comorbidity Index Score ◽  
The Real

Aim: Limited data are available on the real-world safety of non-vitamin K antagonist oral anticoagulants (NOACs). The study purpose was to compare the first major bleeding event risk among non valvular atrial fibrillation patients (NVAF) patients newly initiated on dose-adjusted warfarin versus apixaban 5mg BID, dabigatran 150mg BID, or rivaroxaban 20 mg QD. Methods: Retrospective cohort study was conducted using MarketScan® commercial & Medicare supplemental database from 01/2012 to 12/2013. NVAF patients 18+ years with ≥1 year baseline and newly prescribed oral anticoagulant from 01/01/2013 to 12/31/2013 were included. Major bleeding was defined as bleeding requiring hospitalization on the index drug during the supply duration or within 30 days after the last supply day of the last prescription. A Cox proportional hazards model was used to estimate the hazard ratios (HR) of major bleeding adjusted for age, sex, baseline comorbidities and comedications. Results: Among 26,604 patients, 2,057 (7.73%) were newly initiated on apixaban 5mg, 3,768 (14.16%) on dabigatran 150mg, 8,066 (30.32%) on rivaroxaban 20mg and 12,713 (47.79%) on warfarin. Patients initiating warfarin (72.5±11.9 yrs) and apixaban 5mg (67.0±11.4 yrs) were older as compared to rivaroxaban 20mg (65.2±11.4 yrs) and dabigatran 150mg (65.4±11.5 yrs). Patients initiating warfarin had higher CHA 2 DS 2- VASc score (3.22±1.65) and Charlson comorbidity index score (2.37±2.33) (P <0.0001 across all treatments) as compared to those initiating NOACs. After adjusting for baseline characteristics, patients newly initiated on apixaban 5mg BID had significantly lower risk of major bleeding (HR: 0.53, 95% CI: 0.29-0.97, P=0.0399) as compared to those initiated on warfarin (Table). Conclusion: Among newly anticoagulated NVAF patients in the real world setting, as compared to dose adjusted warfarin, only patients initiating on apixaban 5mg BID were associated with significantly lower risk of major bleeding.

Abstract 261: Applying Clinical Trial Data to Real-World: Apixaban, Dabigatran, and Rivaroxaban

2014 ◽  
Vol 7 (suppl_1) ◽  
Author(s):  
Alpesh Amin ◽  
Michael Stokes ◽  
Ning Wu ◽  
Elyse Gatt ◽  
Dinara Makenbaeva ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Trials ◽  
Relative Risk ◽  
Clinical Outcome ◽  
Intracranial Hemorrhage ◽  
Major Bleeding ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Absolute Risk ◽  
The Real

BACKGROUND: Data from randomized controlled trials and a real-world sample of non-valvular atrial fibrillation patients were combined to estimate the absolute effect of each new oral anticoagulant (NOAC, apixaban, dabigatran, and rivaroxaban) versus warfarin on stroke and major bleeding rates in real-world clinical practice. METHODS: Non-valvular atrial fibrillation patients were selected from Medco healthplans during 2007-2010. Reference rates for stroke and major bleeding excluding intracranial hemorrhage (to avoid double counting) were calculated for real-world Medco patients during warfarin use. Real-world event rates for NOACs were estimated by multiplying the corresponding relative risk from the randomized clinical trials by each reference rate. Absolute risk reductions and numbers needed to treat (NNT) or numbers needed to harm (NNH) for each NOAC vs. warfarin were then estimated. Reduction in net clinical outcome was calculated by summing the absolute risk reductions for stroke and major bleeding excluding intracranial hemorrhage for each NOAC versus warfarin. RESULTS: Each NOAC resulted in a reduction in stroke events compared with warfarin in the real-world (TABLE). Apixaban was the only NOAC to reduce the rate of major bleeding excluding intracranial hemorrhage compared with warfarin. The NNT to avoid one net clinical outcome (stroke plus major bleeding excluding intracranial hemorrhage) per year was 32 and 84 for apixaban and dabigatran, respectively. Rivaroxaban resulted in an increase in net clinical outcome (NNH=166). CONCLUSIONS: If relative risk reductions from randomized clinical trials persist in the real-world, apixaban would result in the greatest clinical benefit versus warfarin of all NOACs in terms of stroke and major bleeding excluding intracranial hemorrhage events avoided.

scholarly journals Athn 15: Characterizing the Real-World Use of Direct Oral Anticoagulants in Pediatric Patients - Interim Analysis

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 19-20
Author(s):  
Jennifer G. Davila ◽  
Fernando F. Corrales-Medina ◽  
Dunlei Cheng ◽  
Leslie J. Raffini ◽  
Courtney D Thornburg ◽  
...  
Keyword(s):  
Real World ◽  
Research Funding ◽  
Pediatric Patients ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Safety Monitoring ◽  
Data Safety Monitoring Board ◽  
Advisory Board ◽  
The Real ◽  
The Us

Background: There are currently four direct oral anticoagulants (DOACs) approved for the acute treatment and prevention of venous thromboembolism (VTE) in adults. Pediatric hematologists across the United States (US) are using DOACs for their patients based on extrapolated data from adult studies and recently published phase 3 pediatric-specific studies. (Brandao LR, et al. Blood, 2019 and Male C, et al. Lancet Haematol, 2020.) Because further data regarding DOAC use in children are needed, ATHN 15: Characterizing the Real-World Use of Direct Oral Anticoagulants in Pediatric Patients, was developed and is being sponsored by the American Thrombosis and Hemostasis Network (ATHN). The study is being conducted at ATHN-affiliated sites in the US and aims to characterize the real-world use of DOACs in children diagnosed with VTE. ATHN is a nonprofit network of over 140 federally funded hemophilia treatment centers (HTCs) that provides the infrastructure for clinical research and public health surveillance. Methods: Data being captured includes demographics, clinical characteristics, anticoagulation management, and treatment outcomes (bleeding and recurrent thrombosis) of patients &lt;21 years of age, who have received or are receiving a DOAC since January 1, 2015 for the treatment of an acute VTE episode or prevention of thrombosis recurrence. Data are collected for up to 6 months from the start of DOAC treatment. Results: As of May 31, 2020, 76 patients from 9 sites have been enrolled (see Table 1 for demographics). Deep venous thrombosis (DVT) of the lower extremities or pelvis is the most prevalent VTE (n = 23, 30.26%), followed by DVT of the upper extremity or upper thorax and pulmonary embolism plus VTE (n = 22, 28.95 and n = 13, 17.1% respectively). 82.89% of patients did not have a history of prior VTE at the time of enrollment. Of the 15 patients with a radiologically confirmed anatomic anomaly, Paget Schroetter/Thoracic Outlet Syndrome and May-Turner Syndrome are the most common (n = 6, 40% and n = 4, 26.7%, respectively). Factor V Leiden heterozygosity, reported in 8 patients, is the most prevalent inherited thrombophilia. Forty-eight patients were identified as having a medical risk factor associated with their VTEs. Sixteen (33.3%) were classified as obese and another 13 (27.1%) had a hospital admission stay greater than 7 days and within 30 days prior to the VTE. At least one specific drug or environmental risk factor was reported in 44 patients. Concomitant use of hormonal contraception (currently taking/stopped within 4 weeks prior to VTE) and the presence of a central venous catheter (present at time of VTE or within 30 days prior to VTE) were the most commonly reported (n = 18, 40.9% and n = 15, 34.09%, respectively). Rivaroxaban is the most prescribed DOAC with 59.2% (n = 45) of patients using this agent. Apixaban and dabigatran use is also reported (n = 29; 38.2% and n = 2; 2.6% respectively). Of the 76 patients, 65 received a different anticoagulant prior to starting a DOAC. Enoxaparin and unfractionated heparin are most commonly prescribed prior to the institution of a DOAC regimen (n = 52, 80% and n = 17, 26.2%). Conclusions: Despite lack of an FDA-approved pediatric indication, hematologists in the US are already using DOACs for children with VTE. Most pediatric patients treated with a DOAC are older than 13 years of age, although we anticipate this will change as providers develop more comfort with these drugs. Interestingly, most of these patients were started on a different anticoagulation regimen prior to starting a DOAC. As enrollment continues, ATHN 15 will serve as a resource for pediatric hematologists to characterize the real-world use of DOACs in children. Further analysis will evaluate DOAC-specific utilization, efficacy and adverse events, including heavy menstrual bleeding. Disclosures Davila: Spire Learning: Speakers Bureau; ATHN: Other: Grant Funding. Corrales-Medina:Bayer: Consultancy; Takeda: Consultancy; Octapharma: Consultancy, Speakers Bureau. Raffini:XaTek: Other: Advisory Board; CSL Behring: Other: Advisory Board; HemaBiologics: Other: Advisory Board; Bayer: Other: Advisory Board; Roche: Other: Advisory Board. Thornburg:Sanofi Genzyme: Consultancy, Other: Data Safety Monitoring Board, Research Funding; NovoNordisk: Research Funding; Genentech: Speakers Bureau; Biomarin: Consultancy, Speakers Bureau; Bayer Pharmaceuticals: Research Funding; American Thrombosis and Hemostasis Network: Research Funding; National Hemophilia Foundation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Ironwood Pharmaceuticals: Consultancy, Other: Data Safety Monitoring Board; Bluebird Bio: Consultancy; Spark Therapeutics: Consultancy. OffLabel Disclosure: Apixaban, Rivaroxaban, Dabigatran and Enoxaparin use in the pediatric population.

scholarly journals A Real-world Experience of the Safety and Efficacy of Non-vitamin K Oral Anticoagulants Versus Warfarin in Patients with Non-valvular Atrial Fibrillation— A Single-centre Retrospective Cohort Study in Singapore

2020 ◽  
Vol 49 (11) ◽  
pp. 838-847
Author(s):  
Wen Jun Tiew ◽  
Vivien LX Wong ◽  
Vern Hsen Tan ◽  
Yong Chuan Tan ◽  
Elena MS Lee
Keyword(s):  
Atrial Fibrillation ◽  
Cohort Study ◽  
Vitamin K ◽  
Major Bleeding ◽  
Real World ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Oral Anticoagulants ◽  
Single Centre ◽  
Safety And Efficacy

Introduction: Non-vitamin K oral anticoagulants (NOACs) were shown to have better outcomes than warfarin for non-valvular atrial fibrillation (NVAF). Given limited local real-world data, this study aims to evaluate the safety and efficacy of NOACs versus warfarin for NVAF in Singapore. Methods: This single-centre retrospective cohort study included 439 patients ≥ 21 years old that were newly prescribed with oral anticoagulants (OACs) for NVAF in 2015. Follow-ups for patients upon OAC initiation lasted either for 2 years or until the occurrence of bleeding or thromboembolism event or death (whichever was earlier). Primary endpoints included major bleeding and stroke, while secondary endpoints included overall bleeding and thromboembolic events. Time-to-events was evaluated via Kaplan-Meier survival analysis. Data on time in therapeutic range (TTR) and compliance were analysed. Results: Patients were assigned to 4 groups: warfarin (157, 35.8%), rivaroxaban (154, 35.1%), apixaban (98, 22.3%) and dabigatran (30, 6.8%). With a mean age of 70.8 (±10.8) years old, the population were predominantly males (56.5%) and comprised Chinese (73.8%), Malays (18.7%) and others (7.5%). The rates of stroke per year were 0.7%, 1.7%, 2.2% and 0% for warfarin, rivaroxaban, apixaban and dabigatran, respectively (P=0.411), whereas those of major bleeding were 2.7%, 1.4%, 2.2% and 0% (P=0.560). As compared to warfarin, no significant differences were observed for risks of stroke and of major bleeding for rivaroxaban (adjusted hazard ratio (HR) 4.19, 95% confidence interval (CI) 0.68–26.05, P=0.124 and adjusted HR 0.43, 95% CI 0.12–1.59, P=0.207) and apixaban (adjusted HR 5.33, 95% CI 0.85–33.34, P=0.074 and adjusted HR 1.54, 95% CI 0.39–6.15, P=0.538). Mean TTR was 68.8% (±24.3%) for warfarin. Compliance rates for rivaroxaban, apixaban, and dabigatran were 56.6%, 59.2%, and 44.8% respectively (P=0.177). Conclusion: NOACs were associated with similar stroke and major bleeding rates as warfarin for NVAF. Keywords: Anticoagulant, Asian, atrial fibrillation, compliance, haemorrhage, thrombosis

scholarly journals Gihp-Naco Prospective Registry: Characterization and Care of Major Bleeding in Patients Treated By Direct Oral Anticoagulants

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2877-2877
Author(s):  
Gilles Pernod ◽  
Pierre Albaladejo ◽  
Charles-Marc Samama ◽  
Pierre-Marie Sie ◽  
jean Luc Bosson
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Research Funding ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Phase Iii ◽  
Trauma Patients ◽  
Clotting Factors ◽  
Drug Concentrations ◽  
Few Data

Abstract Introduction: Direct oral anticoagulants, previously new oral anticoagulants (NOACs) had a favorable risk–benefit profile, both for stroke prevention or systemic embolic events in patients with atrial fibrillation (AF), or for venous thromboembolism (VTE) treatment. Although the rate of intracranial hemorrhage is lower, the risk for major bleeding is similar as for warfarin. Only few data are available for the management of major bleeding in clinical practice. The aim of this study is to present preliminary results regarding characterization and care of major bleeding through a French prospective registry. Methods: The GIHP (French Working group on Perioperative hemostasis) – NACO registry is a prospective observatory started in June 2013 in 32 emergency centers in France and Belgium. Only patients treated by NOACs and hospitalized for major bleeding or urgent surgery were registered. Results: In a midterm analysis in June 2014, 339 patients were included, among which 219 for major bleeding. 75 patients were treated by dabigatran (150 mg bid: 81%), and 142 by rivaroxaban (20 mg od: 54%) (2 patients were treated by Apixaban). The mean age was 76.4 +/- 11y, and mean BMI 26.3. Creatinine clearance was lower than 60 ml/min in 65%. Patients were treated for atrial fibrillation (80%) or VTE (20%). Among patients with AF, 67.2% had CHADS2 at 2 or less. 61.6% of patients received concomitantly at least one drug interfering with CYP or Pgp, and 26.9% received another antithrombotic drug at the time of bleeding. Major hemorrhagic sites were gastrointestinal (25%) and intracranial, either spontaneous (20%) or post-trauma (15%). AOD concentrations were determined in 46% of patients. 20% of the patients with major bleeding had a plasma concentration less than 50 ng/ml. As expected, there is no relationship between drug concentrations and standard hemostatic tests such as PT and aPTT. 38.4% of patients received PCC or aPCC, and 25.7% benefited for any additional procedures (surgery, endoscopy, embolization…). 42.2% of bleeding completely stopped after the administration of clotting factors. At 30d of follow up, 9.1% of patients presented a cardiovascular event, and all-cause mortality was 14.2%. Conclusion: This midterm analysis of the GIHP NACO registry shows consistent results with phase III studies, with some particularities compared to clinical trials, especially in the use of PCC. The registry allows the analysis of specific population such as trauma patients and highlights the care of such major hemorrhages. Disclosures Pernod: LFB: Research Funding; CSL: Research Funding; Octapharma: Research Funding. Off Label Use: PCC and aPCC ro reverse effect of antithrombotic drugs. Albaladejo:LFB: Research Funding; CSL: Research Funding; Octapharma: Research Funding. Samama:LFB: Research Funding; CSL: Research Funding; Octapharma: Research Funding. Sie:LFB: Research Funding; CSL: Research Funding; Octapharma: Research Funding. Bosson:LFB: Research Funding; CSL: Research Funding; Octapharma: Research Funding.

Generalizability of clinical trials of advanced melanoma in the real-world, population-based setting

2018 ◽  
Vol 35 (7) ◽  
Author(s):  
Davis Sam ◽  
Gillian Gresham ◽  
Omar Abdel-Rahman ◽  
Winson Y. Cheung
Keyword(s):  
Clinical Trials ◽  
Real World ◽  
Population Based ◽  
Advanced Melanoma ◽  
World Population ◽  
The Real

Treatment and secondary prevention of venous thromboembolism in cancer patients

2012 ◽  
Vol 03 (03) ◽  
pp. 121-125
Author(s):  
I. Pabinger ◽  
C. Ay
Keyword(s):  
Clinical Trials ◽  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Phase Iii ◽  
Patients With Cancer ◽  
Potential Use

SummaryCancer is a major and independent risk factor of venous thromboembolism (VTE). In clinical practice, a high number of VTE events occurs in patients with cancer, and treatment of cancerassociated VTE differs in several aspects from treatment of VTE in the general population. However, treatment in cancer patients remains a major challenge, as the risk of recurrence of VTE as well as the risk of major bleeding during anticoagulation is substantially higher in patients with cancer than in those without cancer. In several clinical trials, different anticoagulants and regimens have been investigated for treatment of acute VTE and secondary prophylaxis in cancer patients to prevent recurrence. Based on the results of these trials, anticoagulant therapy with low-molecular-weight heparins (LMWH) has become the treatment of choice in cancer patients with acute VTE in the initial period and for extended and long-term anticoagulation for 3-6 months. New oral anticoagulants directly inhibiting thrombin or factor Xa, have been developed in the past decade and studied in large phase III clinical trials. Results from currently completed trials are promising and indicate their potential use for treatment of VTE. However, the role of the new oral thrombin and factor Xa inhibitors for VTE treatment in cancer patients still has to be clarified in further studies specifically focusing on cancer-associated VTE. This brief review will summarize the current strategies of initial and long-term VTE treatment in patients with cancer and discuss the potential use of the new oral anticoagulants.

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