Patient outcomes using the European label for dabigatran

2014 ◽  
Vol 111 (05) ◽  
pp. 933-942 ◽  
Author(s):  
Andreas Clemens ◽  
Herbert Noack ◽  
Jorge Ferreira ◽  
Stuart J. Connolly ◽  
Salim Yusuf ◽  
...  
Keyword(s):  
Major Bleeding ◽  
Haemorrhagic Stroke ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Increased Risk ◽  
Life Threatening ◽  
Net Clinical Benefit ◽  
European Society Of Cardiology ◽  
Post Hoc ◽  
The Eu

SummaryIn the RE-LY trial dabigatran 150 mg twice daily (D150) showed significantly fewer strokes, and 110 mg (D110) significantly fewer major bleeding events (MBE) compared to well-controlled warfarin in patients with atrial fibrillation (AF). The European (EU) label currently recommends the use of D150 in AF patients who are aged < 80 years without an increased risk for bleeding (e.g. HAS-BLED score <3) and not on concomitant verapamil. In other patients, D110 is recommended. In this post-hoc analysis of the RE-LY dataset, we simulated how dabigatran (n=6,004) would compare to well-controlled warfarin (n=6,022) used according to the EU label. “EU label simulated dabigatran treatment” was associated with significant reductions in stroke and systemic embolism (hazard ratio [HR] 0.74; 95% confidence interval [CI] 0.60–0.91), haemorrhagic stroke (HR 0.22; 95%CI 0.11–0.44), death (HR 0.86; 95%CI 0.75–0.98), and vascular death (HR 0.80; 95%CI 0.68–0.95) compared to warfarin. Dabigatran was also associated with less major bleeding (HR 0.85; 95%CI 0.73–0.98), life-threatening bleeding (HR 0.72; 95%CI 0.58–0.91), intracranial haemorrhage (HR 0.28; 95%CI 0.17–0.45), and “any bleeds” (HR 0.86; 95%CI 0.81–0.92), but not gastrointestinal major bleeding (HR 1.23; 95%CI 0.96–1.59). The net clinical benefit was significantly better for dabigatran compared to warfarin. In conclusion, this post-hoc simulation of dabigatran usage based on RE-LY trial dataset indicates that “EU label simulated dabigatran treatment” may be associated with superior efficacy and safety compared to warfarin, and are in support of the EU label and the 2012 European Society of Cardiology AF guideline recommendations. Thus, adherence to European label/guideline use results in a clinically relevant benefit for dabigatran over warfarin, for both efficacy and safety.Note: The editorial process for this paper was fully handled by Prof Christian Weber, Editor in Chief.

scholarly journals Thromboprophylactic Efficacy and Safety of Anticoagulants After Arthroscopic Knee Surgery: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 25 ◽  
pp. 107602961988140
Author(s):  
Yang Yu ◽  
Shitao Lu ◽  
Jinpeng Sun ◽  
Wei Zhou ◽  
Hongjian Liu
Keyword(s):  
Major Bleeding ◽  
Bleeding Event ◽  
Control Group ◽  
Controlled Trials ◽  
Number Needed To Treat ◽  
Cochrane Central Register ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Increased Risk ◽  
Significant Difference

To examine the efficacy and safety of anticoagulants after knee arthroscopy (KA), PubMed, EMBASE, databases of Cochrane Central Register of Controlled Trials, and Chinese National Knowledge Infrastructure were searched up to August 2019 for randomized controlled trials (RCT). Seven RCTs including 4097 patients were demonstrated eligible according to the inclusion and exclusion criteria. The efficacy and safety of thromboprophylaxis were assessed and expressed using relative risk (RR) and 95% confidence intervals (95% CIs). The analysis of pooled data showed that anticoagulants group exhibited significant lower overall incidence of symptomatic and asymptomatic venous thromboembolism (VTE; RR = 0.35, 95% CIs: 0.22-0.55, P < .00001), significant higher incidence of all bleeding events (RR = 1.42, 95% CIs: 1.08-1.86, P = .01) compared to control group. However, no significant difference was found in terms of incidence of symptomatic VTE (RR = 0.43, 95% CIs: 0.15-1.21, P = .11) and incidence of major bleeding events (RR = 1.87, 95% CIs: 0.40-8.67, P = .42). The pooled number needed to treat to prevent one symptomatic or asymptomatic VTE was 26, while the pooled number needed to harm to cause one major bleeding event was 869. These results show that anticoagulants can effectively reduce the overall risk of VTE after KA; however, the increased risk of bleeding should be fully considered. Further studies are required to address the risk–benefit calculus and cost-effectiveness of anticoagulants after KA.

Comparative Efficacy and Safety of Duration of Dual Antiplatelet Therapy in Patients with CAD Undergoing Drug-eluting Stent Implantation: A Systematic Review and Network Meta-analysis

2020 ◽  
Vol 26 (44) ◽  
pp. 5739-5745
Author(s):  
Jieqiong Guan ◽  
Wenjing Song ◽  
Pan He ◽  
Siyu Fan ◽  
Hong Zhi ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Major Bleeding ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Drug Eluting Stent ◽  
Efficacy And Safety ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Drug Eluting

Objective: The aim was to evaluate the efficacy and safety of duration of dual antiplatelet therapy (DAPT) for patients who received percutaneous coronary intervention (PCI) with a drug-eluting stent. Background: The optimal duration of DAPT to balance the risk of ischemia and bleeding in CAD patients undergoing drug-eluting stent (DES) implantation remains controversial. Methods: PubMed, Cochrane Library, Web of Science, Clinicaltrials.gov, CNKI and Wanfang Databases were searched for randomized controlled trials of comparing different durations of DAPT after DES implantation. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), and major bleeding, and were pooled by Bayes network meta-analysis. Net adverse clinical and cerebral events were used to estimate the surface under the cumulative ranking (SUCRA) curves. The subgroup analysis based on clinical status, follow-up and area was conducted using traditional pairwise meta-analysis. Results: A total of nineteen trials (n=51,035) were included, involving six duration strategies. The network metaanalysis showed that T2 (<6-month DAPT followed by aspirin, HR:1.51, 95%CI:1.02-2.22), T3 (standard 6-month DAPT, HR:1.47, 95%CI:1.14-1.91), T4 (standard 12-month DAPT, HR:1.41, 95%CI:1.15-1.75) and T5 (18-24 months DAPT, HR:1.47, 95%CI:1.09-1.97) was associated with significantly increased risk of MACCE compared to T6 (>24-month DAPT). However, no significant difference was found in MACCE risk between T1 (<6-month DAPT followed by P2Y12 monotherapy) and T6. Moreover, T5 was associated with significantly increased risk of bleeding compared to T1(RR:3.94, 95%CI:1.66-10.60), T2(RR:3.65, 95%CI:1.32-9.97), T3(RR:1.93, 95%CI:1.21-3.50) and T4(RR:1.89, 95%CI:1.15-3.30). The cumulative probabilities showed that T6(85.0%), T1(78.3%) and T4(44.5%) were the most efficacious treatment compared to the other durations. In the ACS (<50%) subgroup, T1 was observed to significantly reduce the risk of major bleeding compared to T4, but not in the ACS (≥50%) subgroup. Conclusions: Compared with other durations, short DAPT followed by P2Y12 inhibitor monotherapy showed non-inferiority, with a lower risk of bleeding and not associated with an increased MACCE. In addition, the risk of major bleeding increased significantly, starting with DAPT for 18-month. Compared with the short-term treatment, patients with ACS with the standard 12-month treatment have a better prognosis, including lower bleeding rate and the decreased risk of MACCE. Due to study's limitations, the results should be verified in different risk populations.

scholarly journals Peak Thrombin and D-Dimer Levels in Subjects with Severe Hemophilia Receiving Acute Treatment for Bleeding Episodes Experienced during Prophylactic Marstacimab Treatment

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 33-34
Author(s):  
Satyaprakash Nayak ◽  
Sangeeta Raje ◽  
John Teeter ◽  
Lutz Harnisch ◽  
Steven Arkin
Keyword(s):  
Bleeding Episode ◽  
Phase 2 ◽  
Bleeding Events ◽  
Post Hoc Analysis ◽  
On Demand ◽  
Increased Risk ◽  
Phase 2 Study ◽  
Bleeding Episodes ◽  
Post Hoc ◽  
D Dimer

Introduction: Marstacimab is a fully humanized monoclonal immunoglobulin G1 that targets the shared K2 domains of tissue factor pathway inhibitor (TFPI)α and (TFPI)β and is currently in phase 3 development. The intended indication is routine prophylaxis treatment to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B (with or without inhibitors). Factor replacement or bypass treatment for bleeding events may lead to increased levels of peak thrombin and D-dimer associated with an increased risk of thrombosis . In this post hoc analysis of data from a phase 2 study in patients with hemophilia with and without bleeding episodes, receiving prophylactic marstacimab treatment, peak thrombin and D-dimer levels were investigated to assess the changes in these biomarker levels observed after bleeding episodes. Methods: Individual subject data from the phase 2 study (clinicaltrials.gov identifier: NCT02974855)were used for this analysis. Biomarker data for healthy volunteers who received single doses of marstacimab in a phase 1 dose escalation study (clinicaltrials.gov identifier: NCT02531815) were used as control data, as these subjects represent an intact and uncompromised coagulation system. Study subjects in the phase 2 study received subcutaneous (SC) marstacimab at doses of (1) 150 mg once weekly (QW), with a loading dose of 300 mg, (2) 300 mg QW, and (3) 450 mg QW. All subjects with bleeding episodes were identified, along with on-demand treatment administered for each bleeding episode. Treatments permitted for bleeding episodes included activated coagulation factor VIIa, factor VIII, or factor IX; use of activated prothrombin complex concentrate was prohibited. D-dimer and peak thrombin data collected within 3 days after each bleeding episode were used for this analysis. Time profiles of peak thrombin and D-dimer levels were analyzed to assess the effect of bleed treatment. Biomarker profiles were compared between subjects with and without bleeding episodes, as well as with the data from healthy volunteers (n=41). Results: A total of 15 bleeding episodes were reported in 8 of 26 subjects during the study (excluding screening and follow-up). No subject participating in the study showed any relevant increases in D-dimer levels after receiving on-demand treatment for a bleeding episode while receiving regular prophylaxis with marstacimab, compared with levels seen in subjects who did not experience a bleeding episode. Based on the peak thrombin data (see Figure), 150 nM was observed as the upper limit for 18 of 26 subjects who did not experience any bleeding episodes, which was approximately 50% of the 300 nM observed in healthy volunteer controls treated with 450 mg intravenous marstacimab. Transient increases in peak thrombin of &gt;150 nM were observed at several time points in 3 of 8 subjects who experienced bleeding episodes. The highest peak thrombin level reported was approximately 211 nM in one subject receiving marstacimab 300 mg SC QW and factor VIII concentrate on demand during the study. Conclusions: No transient increases in D-dimer could be attributed to the administration of bleeding episode treatment. The transient increases in peak thrombin levels following on-demand treatment for bleeding episodes did not exceed peak thrombin levels seen in subjects without bleeding events or the levels seen in healthy volunteer controls receiving single doses of marstacimab. Based on peak thrombin and D-dimer levels observed in this post hoc analysis, there does not appear to be any indication of an increased risk of thrombosis post administration of acute on-demand bleeding episode treatment while on prophylactic marstacimab therapy at the doses studied. Disclosures Nayak: Pfizer Inc.: Current Employment, Other. Raje:Pfizer Inc.: Current Employment, Other. Teeter:Pfizer Inc.: Current Employment. Harnisch:Pfizer Inc.: Current Employment, Other. Arkin:Pfizer: Current Employment, Current equity holder in publicly-traded company, Other: own stock/options in the company.

scholarly journals Efficacy and Safety of Long‐Term Antithrombotic Strategies in Patients With Chronic Coronary Syndrome: A Network Meta‐analysis of Randomized Controlled Trials

2021 ◽  
Author(s):  
Houyong Zhu ◽  
Xiaoqun Xu ◽  
Xiaojiang Fang ◽  
Fei Ying ◽  
Liuguang Song ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Coronary Syndrome ◽  
High Risk Factors ◽  
Cerebrovascular Events

Background Long‐term antithrombotic strategies for patients with chronic coronary syndrome with high‐risk factors represent an important treatment dilemma in clinical practice. Our aim was to conduct a network meta‐analysis to evaluate the efficacy and safety of long‐term antithrombotic strategies in patients with chronic coronary syndrome. Methods and Results Four randomized studies were included (n=75167; THEMIS [Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study], COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies], PEGASUS‐TIMI 54 [Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54], and DAPT [Dual Anti‐platelet Therapy]). The odds ratios (ORs) and 95% CIs) were calculated as the measure of effect size. The results of the network meta‐analysis showed that, compared with aspirin monotherapy, the ORs for trial‐defined major adverse cardiovascular and cerebrovascular events were 0.86; (95% CI, 0.80–0.93) for ticagrelor plus aspirin, 0.89 (95% CI, 0.78–1.02) for rivaroxaban monotherapy, 0.74 (95% CI, 0.64–0.85) for rivaroxaban plus aspirin, and 0.72 (95% CI, 0.60,–0.86) for thienopyridine plus aspirin. Compared with aspirin monotherapy, the ORs for trial‐defined major bleeding were 2.15 (95% CI, 1.78–2.59]) for ticagrelor plus aspirin, 1.51 (95% CI, 1.23–1.85) for rivaroxaban monotherapy, and 1.68 (95% CI, 1.37–2.05) for rivaroxaban plus aspirin. For death from any cause, the improvement effect of rivaroxaban plus aspirin was detected versus aspirin monotherapy (OR, 0.76; 95% CI, 0.65–0.90), ticagrelor plus aspirin (OR, 0.79; 95% CI, 0.66–0.95), rivaroxaban monotherapy (OR, 0.82; 95% CI, 0.69–0.97), and thienopyridine plus aspirin (OR, 0.58; 95% CI, 0.41–0.82) regimens. Conclusions All antithrombotic strategies combined with aspirin significantly reduced the incidence of major adverse cardiovascular and cerebrovascular events and increased the risk of major bleeding compared with aspirin monotherapy. Considering the outcomes of all ischemic and bleeding events and all‐cause mortality, rivaroxaban plus aspirin appears to be the preferred long‐term antithrombotic regimen for patients with chronic coronary syndrome and high‐risk factors.

scholarly journals Tinzaparin in Cancer and Renal Impairment: A Systematic Review Focusing on Safety

2020 ◽  
Author(s):  
Ioannis Vathiotis ◽  
Nikolaos Syrigos ◽  
Evangelos Dimakakos
Keyword(s):  
Systematic Review ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Cancer Patients ◽  
Major Bleeding ◽  
Severe Renal Impairment ◽  
Vitamin K Antagonists ◽  
Bleeding Events ◽  
Increased Risk ◽  
Therapeutic Doses

Abstract Purpose: Low-molecular-weight heparins are approved for primary and secondary venous thromboembolism prevention. The purpose of this systematic review is to provide an update regarding the safety profile of tinzaparin sodium, prescribed either as a prophylactic or as a therapeutic regimen for VTE in cancer patients and individuals suffering from renal impairment. Method: We identified and studied clinical studies from 2000 until 2020, reporting safety outcomes for cancer patients and individuals with renal impairment receiving either prophylactic or therapeutic doses of tinzaparin. Results: In patients with cancer major bleeding rates fluctuate between 0.8% and 7%; reported major bleeding rates for non-cancer patients with renal impairment on prophylactic tinzaparin regimens were 0%. Non-cancer patients on therapeutic tinzaparin regimens exhibited major bleeding in 0 to 2.3% of cases; major bleeding rates were higher for cancer patients with renal impairment receiving therapeutic doses of tinzaparin (4.3 to 10%). Patients on tinzaparin exhibit significantly lower rates of clinically relevant nonmajor bleeding events in comparison with those on vitamin K antagonists. Bioaccumulation of tinzaparin is not correlated with age, body weight or creatinine clearance. Periodic administration of either prophylactic or therapeutic doses of tinzaparin does not result in bioaccumulation, even in patients with severe renal impairment and creatinine clearance < 20 ml/min. Conclusion: Tinzaparin is safe and can be used without dose adjustment in patients with severe renal impairment and creatinine clearance > 20 ml/min. Tinzaparin represents a thoroughly studied and safe choice for special populations at increased risk for thrombosis and bleeding.

Efficacy of Dual Antiplatelet Treatment in Minor stroke or TIA Patients with Multiple Acute Infarctions and Lower Level of Stress Hyperglycemic Marker – A Post-hoc Analysis of a Randomized Control Trial

2020 ◽  
Author(s):  
Yue Suo ◽  
Jing Jing ◽  
Anxin Wang ◽  
Yijun Zhang ◽  
Hongyu Zhou ◽  
...  
Keyword(s):  
Minor Stroke ◽  
Efficacy And Safety ◽  
Antiplatelet Treatment ◽  
Bleeding Events ◽  
Vascular Events ◽  
Stress Hyperglycemia ◽  
Post Hoc Analysis ◽  
Acute Infarction ◽  
Post Hoc ◽  
Dual Antiplatelet Treatment

Abstract Background We intended to investigate how the interaction between glycemic status and infarction pattern affected the efficacy and safety of dual antiplatelet treatment in minor stroke or transient ischemic attack (TIA) patients.Methods This post-hoc analysis of the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events (CHANCE) study included 797 patients with complete data of stress hyperglycemia markers (fasting plasma glucose (FPG)/glycated albumin (GA) ratio) and Magnetic Resonance Imaging work-up. The primary outcome is a 90-day new stroke (ischemic or hemorrhagic). Other endpoints included combined vascular events and bleeding events at 90 days. We used multivariable Cox regression models to evaluate the influence of stress hyperglycemia status × infarction pattern (Multiple acute infarctions (MAI), Single acute infarction (SAI) and No acute infarction (NAI)) on the efficacy and safety of clopidogrel plus aspirin treatment.Results Among 797 patients, the median age was 63.1 years, and 64.9% of the patients were male. Within the 90-day after randomization, 73 (9.2%) new strokes 75 (9.4%) combined vascular events, and 17 (2.1%) bleeding events occurred. Dual antiplatelet treatment significantly reduced new stroke and combined vascular events in patients with lower FPG/GA ratio (lower than the median of FPG/GA ratio) and multiple acute infarctions, after adjusted for all potential confounders (11.9% vs. 23.3%, adjusted HR(95% confidence interval, CI): 0.240(0.080–0.713)). No significant reductions of recurrence or occurrence of combined vascular events were seen in the other three groups (NAI or SAI with lower FPG/GA ratio; NAI or SAI with higher FPG/GA ratio and MA with higher FPG/GA ratio). The proportion of bleeding events was similar among treatment groups regardless of the FPG/GA ratio or infarction pattern.Conclusions Clopidogrel plus aspirin treatment was associated with reduced 90-day new stroke or combined vascular events in patients with multiple acute infarctions and lower FPG/GA ratio, without increasing the risk of bleeding events.

Efficacy and Safety of Edoxaban Versus Enoxaparin for the Prevention of Venous Thromboembolism Following Total Hip Arthroplasty: STARS J-V trial

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3320-3320 ◽  
Author(s):  
Takeshi Fuji ◽  
Satoru Fujita ◽  
Shintaro Tachibana ◽  
Yohko Kawai ◽  
Yukihiro Koretsune ◽  
...  
Keyword(s):  
Total Hip Arthroplasty ◽  
Major Bleeding ◽  
Thromboembolic Events ◽  
Primary Efficacy ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Primary Efficacy Outcome ◽  
Treatment Groups ◽  
Efficacy Outcome ◽  
Lead Investigator

Abstract Abstract 3320 Introduction: Edoxaban is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events. The aim of this non-inferiority trial was to determine the efficacy and safety of edoxaban compared with enoxaparin sodium (enoxaparin) after total hip arthroplasty (THA) in Japan. Methods: This was a randomized, double-blind, double-dummy, enoxaparin-controlled, multicenter trial. Patients were randomized to oral edoxaban 30 mg once daily (QD) or subcutaneous enoxaparin 2,000 IU, equivalent to 20 mg, twice daily (BID) for 11 to 14 days. Edoxaban was initiated 6–24 hours after surgery and enoxaparin was initiated 24–36 hours after surgery which is the Japanese standard of care. The primary efficacy outcome was the composite of symptomatic and asymptomatic deep vein thrombosis (DVT), and pulmonary embolism (PE). The primary safety outcome was the incidence of major and clinically relevant non-major bleeding. Results: A total of 610 patients were randomized. There were no clinically relevant differences in baseline characteristics between the treatment groups. The mean age was 62.8 years and mean body weight was 57.4 kg (Efficacy analysis set). The primary efficacy outcome occurred in 6 of 255 (2.4%) patients receiving edoxaban and 17 of 248 (6.9%) patients receiving enoxaparin (relative risk reduction=65.7%; absolute risk difference -4.5%, 95% CI, -8.6% to -0.9%; P<0.001 for non-inferiority; P=0.0157 for superiority). The thromboembolic events were all asymptomatic DVT (Table). No symptomatic DVT or PE was observed in both treatment groups. The incidence of major and clinically relevant non-major bleeding events was 2.6% (8/303) vs 3.7% (11/301) in the edoxaban and enoxaparin groups, respectively (P=0.475). Major bleeding occurred in 0.7% of the edoxaban group and 2.0% of the enoxaparin group. The rates of elevated serum aminotransferase levels of more than 3 times the upper limit of normal was 2.6% with edoxaban versus 10% with enoxaparin. Conclusions: The STARS J-V trial demonstrated that oral edoxaban 30 mg QD has efficacy superior to enoxaparin 2,000 IU BID in the prevention of thromboembolic events following THA and is associated with a similar incidence of major and clinically relevant non-major bleeding events. Disclosures: Fuji: Astellas: Consultancy; Showa Ikakogyo: Consultancy; Daiichi Sankyo: Consultancy; Bayer: Consultancy. Fujita:Daiichi Sankyo: Consultancy; Astellas: Consultancy; GlaxoSmithkline: Consultancy. Tachibana:Daiichi Sankyo: Consultancy. Kawai:Daiichi Sankyo: Consultancy; Toyama Chemical: Consultancy. Koretsune:Daiichi Sankyo: Consultancy, National Lead Investigator. Yamashita:Daiichi Sankyo: Consultancy, National Lead Investigator; Otsuka Pharmaceutical: Paid instructor; Sanofi-aventis: Paid instructor; Teijin Pharma: Paid instructor. Nakamura:Daiichi Sankyo: Consultancy; GlaxoSmithkline: Consultancy; Astellas: Consultancy.

The Effectiveness and Safety of Direct Oral Anticoagulants (DOACs) Vs. Traditional Anticoagulants in Patients with Cirrhosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5015-5015
Author(s):  
Justin Hum ◽  
Janice Jou ◽  
Thomas G. Deloughery ◽  
Joseph Shatzel
Keyword(s):  
Major Bleeding ◽  
Conflicts Of Interest ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Complications ◽  
Efficacy And Safety ◽  
Recurrent Thrombosis ◽  
Bleeding Events ◽  
Cirrhotic Patients

Abstract Introduction: The coagulopathy associated with cirrhosis is complex and places patients at risk for both bleeding and thrombosis. Direct oral anticoagulants (DOACs) have been shown to have superior efficacy and safety compared to vitamin K antagonists; however their efficacy and safety in cirrhotic patients is not clear. The aim of this study is to retrospectively compare the effectiveness and bleeding complications of DOACs as compared to traditional anticoagulants in cirrhotic patients. Methods: This study was a retrospective review of patients treated at a single academic center between 2012-2015 who were prescribed a DOAC (apixaban or rivaroxaban), or a traditional anticoagulant (warfarin or low molecular weight heparin), with an ICD-9 code for the diagnosis of cirrhosis. The primary outcomes of interest are recurrent thrombosis or stroke (efficacy failure), or bleeding events (safety failure). Major bleeds were characterized as fatal bleeding, symptomatic bleeding in critical organ area, or bleeding causing a fall in hemoglobin level >2 or leading to transfusion of 2+ units of packed red blood cells. Results: During the study period, 27 cirrhotic patients were prescribed a DOAC and 18 were prescribed a traditional anticoagulant (either LMWH or warfarin). Both groups had similar total bleeding events (8 DOAC vs. 10 traditional anticoagulation, p = 0.12). There were significantly less major bleeding episodes in the DOAC group, (1 (4%) vs. 5 (28%), p = 0.03) and less intracranial bleeding (3 (17% ) vs. 0 (0%) p=0.06). Recurrent thrombosis or stroke occurred in 1 (4%) patient in the DOAC group and 1 (6%) patient in the traditional group (p = 1.0). Conclusions: Anticoagulation with DOACs in cirrhotic patients may be as safe as traditional anticoagulants with respect to bleeding events. Patients with cirrhosis at our center prescribed DOACs had less major bleeding events, while maintaining efficacy at preventing stroke or recurrent thrombosis. Table Table. Disclosures No relevant conflicts of interest to declare.

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.

Calculation of HAS-BLED Score Is Useful for Early Identification of Venous Thromboembolism Patients at High Risk for Major Bleeding Events: A Prospective Outpatients Cohort Study

2017 ◽  
Vol 44 (04) ◽  
pp. 348-352 ◽  
Author(s):  
Reinhard Raggam ◽  
Franz Hafner ◽  
Alexander Avian ◽  
Gerald Hackl ◽  
Gerhard Cvirn ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Odds Ratio ◽  
Bleeding Complications ◽  
Minor Bleeding ◽  
Prospective Evaluation ◽  
Bleeding Events ◽  
Increased Risk ◽  
Major Bleeding Events

AbstractThe aim of this study was prospective evaluation of the performance of the HAS-BLED score in predicting major bleeding complications in a real-world outpatient cohort, during long-term anticoagulation for venous thromboembolism (VTE), treated with a broad spectrum of anticoagulants. We analyzed 111 outpatients objectively diagnosed with VTE and treated long-term with various anticoagulants. Patients were grouped in three cohorts based on the anticoagulant regimen. Calculation of the HAS-BLED score and documentation of bleeding events were performed every 6 months for 1 year. Patients with a HAS-BLED score ≥ 3 had an increased risk for major bleeding events (odds ratio [OR]: 13.05, 95% confidence interval [CI]: 0.96–692.58, p = 0.028) and a trend to higher risk for minor bleeding events as well (OR: 2.25, 95% CI: 0.87–5.85, p = 0.091) when compared with patients with a HAS-BLED score < 3.This indicates that a HAS-BLED score ≥ 3 allows for identification of patients with VTE on long-term anticoagulation at an increased risk for major bleeding events, irrespective of the anticoagulant agent used.

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