Incidence of Recurrent Thromboembolic and Bleeding Complications Among Patients With Venous Thromboembolism in Relation to Both Malignancy and Achieved International Normalized Ratio: A Retrospective Analysis

2000 ◽  
Vol 18 (17) ◽  
pp. 3078-3083 ◽  
Author(s):  
Barbara A. Hutten ◽  
Martin H. Prins ◽  
Michael Gent ◽  
Jeff Ginsberg ◽  
Jan G. P. Tijssen ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Retrospective Analysis ◽  
Vitamin K ◽  
Major Bleeding ◽  
Randomized Clinical Trials ◽  
Oral Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
International Normalized Ratio ◽  
Bleeding Complications ◽  
Venous Thromboembolic

PURPOSE: Initial heparinization followed by vitamin K antagonists is the treatment of choice for patients with venous thromboembolism. There is controversy whether known malignancy is a risk factor for recurrences and bleeding complications during this treatment. Furthermore, the incidence of such events in these patients is dependent on the achieved International Normalized Ratio (INR). The aim of this study was to assess the incidence of venous thromboembolic recurrence and major bleeding among patients with venous thromboembolism in relation to both malignancy and the achieved INR.PATIENTS AND METHODS: In a retrospective analysis, the INR-specific incidence of venous thromboembolic and major bleeding events during oral anticoagulant therapy was calculated separately for patients with and without malignancy. Eligible patients participated in two multicenter, randomized clinical trials on the initial treatment of venous thromboembolism. Patients were initially treated with heparin (standard or low-molecular weight). Treatment with vitamin K antagonists was started within 1 day and continued for 3 months, with a target INR of 2.0 to 3.0.RESULTS: In 1,303 eligible patients (264 with malignancy), 35 recurrences and 12 bleeds occurred. Patients with malignancy, compared with nonmalignant patients, had a clinically and statistically significantly increased overall incidence of recurrence (27.1 v 9.0, respectively, per 100 patient-years) as well as bleeding (13.3 v 2.1, respectively, per 100 patient-years). In both groups of patients, the incidence of recurrence was lower when the INR was above 2.0 compared with below 2.0.CONCLUSION: Although adequately dosed vitamin K antagonists are effective in patients with malignant disease, the incidence of thrombotic and bleeding complications remains higher than in patients without malignancy.

scholarly journals INR Stability, Clinical Importance, and Predictors in Patients With Atrial Fibrillation and Venous Thromboembolism Receiving Vitamin K Antagonists

2016 ◽  
Vol 32 (6) ◽  
pp. 253-259
Author(s):  
C. Michael White
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Vitamin K ◽  
Systematic Reviews ◽  
Randomized Clinical Trials ◽  
Vitamin K Antagonists ◽  
Bleeding Event ◽  
The United States ◽  
Bleeding Complications ◽  
Anticoagulation Clinics

Objective: Compare and contrast systematic reviews/meta-analyses assessing the time in the therapeutic range (TTR) for vitamin K antagonists (VKAs), clinical impact, and predictors. Data Sources: OVID MEDLINE search (1980-June 1, 2016) using the terms “vitamin K antagonist or warfarin” and “systematic review or meta-analysis” with backwards citation tracking from procured articles. Study Selection and Data Extraction: Search results were limited to systematic reviews assessing TTR with VKAs in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). Data Synthesis: Six systematic reviews assessed TTR (4 in AF, 2 in VTE), and 3 of those assessed control at the time of a thrombotic or bleeding event (2 in AF, 1 in VTE). In patients on VKAs, greater TTR is correlated with fewer thromboembolic events and bleeding complications. VKA naïve patients have a harder time maintaining TTR than those with a previous knowledge of the likely therapeutic dose. Patients in the United States spend less TTR than those in other countries. Randomized clinical trials and anticoagulation clinics achieve greater TTR than those treated outside of these settings. The overall TTR has not improved from the first systematic reviews to the newest ones even though they were conducted 10 years apart and contained many new studies. Also, TTR in AF and VTE is similar. Conclusions: TTR is an important metric of VKA efficacy and safety and needs to be optimized. Many factors such as being VKA naïve can compromise TTR, and the use of anticoagulation clinics to optimize therapy is an important approach.

Management and outcome of major bleeding in patients receiving vitamin K antagonists for venous thromboembolism

2018 ◽  
Vol 171 ◽  
pp. 74-80 ◽  
Author(s):  
Farès Moustafa ◽  
Alexander Stehouwer ◽  
Pieter Kamphuisen ◽  
Joan Carles Sahuquillo ◽  
Ángel Sampériz ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists

scholarly journals Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and cancer a meta-analysis

2020 ◽  
Author(s):  
Marco Valerio Mariani ◽  
Michele Magnocavallo ◽  
Martina Straito ◽  
Agostino Piro ◽  
Paolo Severino ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Efficacy And Safety

Abstract Background Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

Selection, management, and outcome of vitamin K antagonist-treated patients with atrial fibrillation not switched to novel oral anticoagulants

2015 ◽  
Vol 114 (11) ◽  
pp. 1076-1084 ◽  
Author(s):  
Franziska Michalski ◽  
Luise Tittl ◽  
Sebastian Werth ◽  
Ulrike Hänsel ◽  
Sven Pannach ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Major Bleeding ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Case Fatality ◽  
Bleeding Risk ◽  
Vitamin K Antagonist ◽  
Bleeding Complications ◽  
Treatment Rate

SummaryAtrial fibrillation (AF) patients treated with well-controlled vitamin K antagonists (VKAs) may benefit less from non-vitamin K antagonist oral anticoagulants (NOACs) because they are supposed to be at low risk of thromboembolic and bleeding complications. However, little is known about the selection, management, and outcome of such “stable” VKA patients in current practice. We assessed characteristics, VKA persistence and 12 months' outcome of AF patients selected for VKA continuation. On March 1, 2013, the Dresden NOAC registry opened recruitment of patients continuing on VKA for sites that had been actively recruiting AF patients treated with NOACs in the prior 18 months. Patient characteristics were compared with those of NOAC patients from the same sites. Four hundred twenty-seven VKA patients had a significantly lower bleeding risk profile compared with 706 patients selected for NOAC treatment. For VKA, international normalised ratio time-in-therapeutic range before enrolment was 71% and increased to 75% during a mean follow-up of 15 months. Rates of stroke/transient ischaemic attack/systemic embolism were 1.3/100 patient-years (intention-to-treat) and 0.94/100 patient-years (as-treated). On-treatment rate of ISTH major bleeding was 4.15/100 patient-years (95% CI 2.60–6.29) with a case-fatality rate of 16.3% (all-cause mortality at day 90 after major bleeding). In conclusion, in daily care, AF patients selected for VKA therapy are healthier than those treated with NOAC, demonstrate a high quality of anticoagulant control and very low stroke rates. However, despite adequate patient selection and INR control, the risk of major VKA bleeding is unacceptably high and bleeding outcome is poor.

scholarly journals Practice-derived data on non-vitamin K antagonist oral anticoagulant therapy to complement observations from randomized trials

2020 ◽  
Vol 22 (Supplement_I) ◽  
pp. I1-I12
Author(s):  
Magdalena Domek ◽  
Jakub Gumprecht ◽  
Wern Yew Ding ◽  
Gregory Y H Lip ◽  
Deirdre A Lane
Keyword(s):  
Vitamin K ◽  
Randomized Clinical Trials ◽  
Oral Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
Strong Support ◽  
Vitamin K Antagonist ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Increased Risk ◽  
Comparative Review

Abstract Anticoagulation is fundamental in the management of patients with atrial fibrillation (AF). The study aims to provide a comparative review of the major phase III randomized clinical trials (RCTs) and real-world data (RWD) from reliable, high-grade Phase IV studies that assess the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) vs. vitamin K antagonists (VKAs). Observational studies based on nationwide or health insurance database records on the use of NOACs vs. VKAs in patients with AF were included. We performed a comparison of the efficacy and safety characteristics associated with NOACs vs. VKAs in RCTs and RWD. Although RCTs provide strong support for evidence-based practice, RWD may be used to reflect the broader picture of various clinical settings, provide supplementary insight and fulfil knowledge gaps. Both study types confirmed the safety and efficacy of NOACs in preventing stroke and thromboembolism in patients with AF. In comparison to VKAs, NOACs were associated with reduced risk of ischaemic events and lower rates of adverse events such as major bleeding or intracranial haemorrhage. Administration of NOACs might be associated with increased risk of dose-related gastrointestinal bleeding and myocardial ischaemic events, especially in the early treatment period after switching from VKAs. Special care should be taken in challenging clinical situations like severe renal or hepatic impairment when the treatment regimen needs to be considered individually. Randomized clinical trial and RWD studies are complementary and present comparable findings, affirming that NOACs are safe and effective for anticoagulation of patients with AF in daily clinical practice.

Vitamin K Antagonists Compared to Low-Molecular-Weight Heparins for Treatment of Cancer-Associated Venous Thromboembolism: An Observational Study in Routine Clinical Practice

2017 ◽  
Vol 117 (11) ◽  
pp. 2163-2167 ◽  
Author(s):  
Paul den Exter ◽  
José Hooijer ◽  
Tom van der Hulle ◽  
Julien van Oosten ◽  
Olaf Dekkers ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Clinical Practice ◽  
Venous Thromboembolism ◽  
Vitamin K ◽  
Major Bleeding ◽  
Routine Clinical Practice ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Patients With Cancer ◽  
Recurrent Vte

AbstractSince several trials have demonstrated that low-molecular-weight-heparin (LMWH) is superior to vitamin K antagonist (VKA) in preventing recurrent venous thromboembolism (VTE) in patients with cancer-associated VTE, guidelines now recommend LMWH monotherapy in this setting. We evaluated whether this shift resulted in improved outcomes in routine clinical practice. We performed a cohort study of consecutive patients with cancer-associated VTE during 2001 and 2010. We compared the risks for recurrent VTE, major bleeding and mortality between patients diagnosed before and after 2008 during a 6-month routine follow-up. A total of 381 patients were included, of which 234 (61.4%) were diagnosed before 2008. Before 2008, 23% of the patients were treated with LMWH; thereafter, this percentage was higher: 67%. The 6-month incidence for recurrent VTE was 8.6% in patients diagnosed before 2008 versus 7.5% for patients diagnosed after 2008 (risk difference [RD]: −1.1%; 95% confidence interval [CI]: −6.3, 5.3). The respective risks for major bleeding were 6.4 versus 4.8% (RD: −1.6%; 95% CI: −3.8 to 5.8), and 39.7 versus 41.5% (RD: 1.8%; 95% CI: −8.8, 12) for overall mortality. The mean time in therapeutic range (TTR) of patients treated with VKA was 61%. Despite a clear shift toward LMWH as agent of choice for cancer-associated VTE, we did not observe a clear improvement in terms of recurrent VTE and bleeding complications.

scholarly journals Selective serotonin reuptake inhibitor use is associated with major bleeding during treatment with vitamin K antagonists: results of a cohort study

2021 ◽  
Author(s):  
Sanne Bakker ◽  
Louise Burggraaf ◽  
MJHA Kruip ◽  
Felix van der Meer ◽  
WM Lijfering ◽  
...  
Keyword(s):  
Vitamin K ◽  
Major Bleeding ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Cox Regression ◽  
Conditional Logistic Regression ◽  
Vitamin K Antagonists ◽  
Selective Serotonin ◽  
Bleeding Complications ◽  
Increased Risk

Aims: To determine whether Selective serotonin reuptake inhibitors (SSRIs) cause major bleeding during vitamin K antagonist (VKA) treatment and investigate the possible mechanisms behind this interaction. Methods: Information on SSRI use and bleeding complications was obtained from patient records at the Anticoagulation Clinics of Leiden and Rotterdam of VKA initiators between 2006 and 2018. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high INR (≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9 inhibitors. Results: 58,918 patients were included, of whom 1504 were SSRI users. SSRI initiation versus non-use was associated with a 2.41-fold (95% confidence interval [CI] 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95%CI 1.33-7.43) among CYP2C9 inhibiting SSRIs. SSRI use versus non-use was associated with a 1.22-fold (95%CI 0.99-1.50) increased risk for major bleeding in all SSRI users, which was 1.31-fold (95%CI 0.62-2.72) in CYP2C9 inhibiting SSRIs compared to non-users. Conclusion: SSRIs are associated with an increased risk of high INR and major bleeding. These risks were slightly more elevated for CYP2C9 inhibiting SSRI users, suggesting that this was due to a pharmacokinetic interaction (by CYP2C9 inhibition) as well as a pharmacodynamic effect of SSRIs on platelet activation.

High Soluble Thrombomodulin Is Associated with an Increased Risk of Major Bleeding during Treatment with Oral Anticoagulants: A Case–Cohort Study

2020 ◽  
Author(s):  
Myrthe M. A. Toorop ◽  
Nienke van Rein ◽  
Suzanne C. Cannegieter ◽  
Felix J. M. van der Meer ◽  
Pieter H. Reitsma ◽  
...  
Keyword(s):  
Cohort Study ◽  
Vitamin K ◽  
Major Bleeding ◽  
Cox Regression ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
International Normalized Ratio ◽  
Soluble Thrombomodulin ◽  
Major Bleed ◽  
Increased Risk

Abstract Background Major bleeding occurs in 1 to 3% of patients treated with oral anticoagulants per year. Biomarkers may help to identify high-risk patients. A proposed marker for major bleeding while using anticoagulants is soluble thrombomodulin (sTM). Methods Plasma was available from 16,570 patients of the BLEEDS cohort that consisted of patients who started treatment with vitamin K antagonists between 2012 and 2014. A case–cohort study was performed including all patients with a major bleed (n = 326) during follow-up and a random sample of individuals selected at baseline (n = 652). Plasma sTM levels were measured and stratified by percentiles. Patients were also categorized by international normalized ratio (INR). Adjusted hazard ratios (for age, sex, hypertension, and diabetes) with 95% confidence intervals (CIs) were estimated by means of Cox regression. Results Plasma sTM levels were available for 263 patients with a major bleed and 538 control subjects. sTM levels were dose-dependently associated with risk of major bleeding, with a 1.9-fold increased risk (95% CI: 1.1–3.1) for levels above the 85th percentile versus the <25th percentile. A high INR (≥4) in the presence of high (≥70th percentile) sTM levels was associated with a 7.1-fold (95% CI: 4.1–12.3) increased risk of major bleeding, corresponding with a bleeding rate of 14.1 per 100 patient-years. Conclusion High sTM levels at the start of treatment are associated with major bleeding during vitamin K antagonist treatment, particularly in the presence of a high INR.

Management of Oral Anticoagulant-associated Intracerebral Hemorrhage

2018 ◽  
Vol 1 (2) ◽  
pp. 114-125
Author(s):  
Corina Epple ◽  
Thorsten Steiner
Keyword(s):  
Vitamin K ◽  
Oral Anticoagulant ◽  
Anticoagulant Activity ◽  
Oral Anticoagulant Therapy ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Clinical Problem ◽  
International Normalized Ratio ◽  
Bleeding Management ◽  
Number Of Patients

Introduction: Oral anticoagulant-associated intracerebral hemorrhages (OAC-ICHs) account for nearly 20% of all ICH and are associated with high mortality. The number of patients with an indication for oral anticoagulant therapy (OAT) is increasing with the aging population; therefore, despite the improved safety profile of non-vitamin K oral anticoagulants (NOACs), the number of patients with OAC-ICH will increase. OAT was simplified with the introduction of NOACs, which are easy to handle and show a favorable risk-benefit profile. The rate of ICH is lower than for vitamin K antagonists (VKA) and routine coagulation testing is not required. Nevertheless, OAC-ICH does occur and is still a devastating disease, thus representing the most feared complication in OAT, irrespective of treatment with VKA or NOAC. Purpose: The aim of this article is to address the clinical problem of bleeding management in patients with ICH due to OAC and will consider anticoagulation with NOAC and VKA. Recommendations: Restoring coagulation as soon as possible is the main goal and, therefore, knowledge of the actual coagulation status is essential. In VKA-associated ICH, the international normalized ratio (INR) should be lowered to below 1.3. However, laboratory measurement of anticoagulant activity in NOAC patients is more complex, rendering OAC-ICH treatment more complicated. The best assays are specialized and not widely available, whereas more accessible tests such as prothrombin time and activated partial thromboplastin time have important limitations. For VKA-ICH, prothrombin complex concentrate (PCC) should be administered to reverse the INR. For dabigatran-related ICH, 5 g idarucizumab should be administered. For factor Xa inhibitors, PCC is recommended in the absence of andexanet alfa as soon as an OAC-related ICH evolves. Resuming OAC after ICH should be considered, depending on risk factors and a risk-benefit evaluation.

Sign in / Sign up

Export Citation Format

Share Document