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M H Prins - One of the best experts on this subject based on the ideXlab platform.
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duration of treatment with Vitamin K Antagonists in symptomatic venous thromboembolism
Cochrane Database of Systematic Reviews, 2014Co-Authors: Saskia Middeldorp, M H Prins, B A HuttenAbstract:BACKGROUND: Currently, the most frequently used secondary treatment for patients with venous thromboembolism is Vitamin K Antagonists targeted at an INR of 2.5 (range 2.0 to 3.0). However, based on the continuing risK of bleeding and uncertainty regarding the risK of recurrent venous thromboembolism, there is discussion on the proper duration of treatment with Vitamin K Antagonists for these patients. Recently, several studies were published in which the risK and benefits of different durations of oral anticoagulants were compared in patients with venous thromboembolism. OBJECTIVES: The objective of this review was to evaluate efficacy and safety of different durations of treatment with Vitamin K Antagonists in patients with symptomatic venous thromboembolism. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 3, 2005). The Specialised Register is constructed from electronic searches of MEDLINE (from inception to October 2005) and EMBASE (inception to October 2005) and through handsearching relevant journals. In addition, we also contacted colleagues for details of trials. The last searches were carried out on 11 October 2005. SELECTION CRITERIA: Randomized controlled clinical trials comparing different durations of treatment with Vitamin K Antagonists in patients with symptomatic venous thromboembolism. DATA COLLECTION AND ANALYSIS: Two reviewers (BH and MP) extracted the data and assessed the quality of the trials independently. MAIN RESULTS: Eight studies with a total of 2994 patients were included. A consistent reduction in the risK of recurrent events was observed during prolonged treatment with Vitamin K Antagonists (OR 0.18; 95% CI 0.13 to 0.26) independent of the period elapsed since the index thrombotic event. A 'rebound' phenomenon, i.e. an excess of recurrences shortly after cessation of the prolonged treatment was not observed (OR 1.24; 95% CI 0.91 to 1.69). In addition, a substantial increase in bleeding complications was found during the entire period after randomization (OR 2.62; 95% CI 1.48 to 4.61). AUTHORS' CONCLUSIONS: In conclusion, this meta-analysis shows that treatment with Vitamin K Antagonists reduces the risK of recurrent venous thromboembolism for as long as it is used. However, the absolute risK of recurrent venous thromboembolism declines over time, while the risK for major bleeding remains. Thus, the efficacy of Vitamin K antagonist administration decreases over time since the index event
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Duration of treatment with Vitamin K Antagonists in symptomatic venous thromboembolism.
The Cochrane database of systematic reviews, 2006Co-Authors: B A Hutten, M H PrinsAbstract:Currently, the most frequently used secondary treatment for patients with venous thromboembolism is Vitamin K Antagonists targeted at an INR of 2.5 (range 2.0 to 3.0). However, based on the continuing risK of bleeding and uncertainty regarding the risK of recurrent venous thromboembolism, there is discussion on the proper duration of treatment with Vitamin K Antagonists for these patients. Recently, several studies were published in which the risK and benefits of different durations of oral anticoagulants were compared in patients with venous thromboembolism. The objective of this review was to evaluate efficacy and safety of different durations of treatment with Vitamin K Antagonists in patients with symptomatic venous thromboembolism. The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 3, 2005). The Specialised Register is constructed from electronic searches of MEDLINE (from inception to October 2005) and EMBASE (inception to October 2005) and through handsearching relevant journals. In addition, we also contacted colleagues for details of trials. The last searches were carried out on 11 October 2005. Randomized controlled clinical trials comparing different durations of treatment with Vitamin K Antagonists in patients with symptomatic venous thromboembolism. Two reviewers (BH and MP) extracted the data and assessed the quality of the trials independently. Eight studies with a total of 2994 patients were included. A consistent reduction in the risK of recurrent events was observed during prolonged treatment with Vitamin K Antagonists (OR 0.18; 95% CI 0.13 to 0.26) independent of the period elapsed since the index thrombotic event. A 'rebound' phenomenon, i.e. an excess of recurrences shortly after cessation of the prolonged treatment was not observed (OR 1.24; 95% CI 0.91 to 1.69). In addition, a substantial increase in bleeding complications was found during the entire period after randomization (OR 2.62; 95% CI 1.48 to 4.61). In conclusion, this meta-analysis shows that treatment with Vitamin K Antagonists reduces the risK of recurrent venous thromboembolism for as long as it is used. However, the absolute risK of recurrent venous thromboembolism declines over time, while the risK for major bleeding remains. Thus, the efficacy of Vitamin K antagonist administration decreases over time since the index event.
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The relationship between adherence and quality of treatment with Vitamin K Antagonists
Journal of Thrombosis and Haemostasis, 2004Co-Authors: Mirjam Locadia, B A Hutten, Mirjam A. G. Sprangers, J. H. H. Van Geest-daalderop, M H PrinsAbstract:Objective To assess the relationship between adherence and quality of treatment with Vitamin K Antagonists. Methods Patients diagnosed with atrial fibrillation and treated with acenocoumarol were eligible. The percentage of time spent in the target range during the last three months was calculated using linear interpolation. Adherence was assessed with a self-report questionnaire. Results Forty patients who spent 100% (high-quality group) and 40 patients who spent less than 50% of time in the target range were approached for the study. Twenty-seven patients with high and 29 patients with low therapeutic quality returned the questionnaire. In the high-quality group, 88% of patients reported to have taKen all prescribed medication in the previous month, 96% reported to have been fully compliant in the previous weeK, and 76% reported to have taKen all their tablets on time in the previous weeK. These percentages were 82, 90, and 72, respectively in the low-quality group. Differences between the groups were not statistically significant. Conclusion The results indicate that adherence is not related to time spent in the therapeutic target range in older patients with atrial fibrillation treated with Vitamin K Antagonists.
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the incidence of recurrent venous thromboembolism after treatment with Vitamin K Antagonists in relation to time since first event a meta analysis
JAMA Internal Medicine, 2003Co-Authors: Carlo J Van Dongen, Roel Vink, Harry R. Büller, B A Hutten, M H PrinsAbstract:BacKground After a first episode of venous thromboembolism, patients are treated with Vitamin K (phytonadione) Antagonists. There are indications that the risK of recurrence after treatment with Vitamin K Antagonists decreases relative to the time since the first event. The aim of the present meta-analysis is to describe the risK of recurrent venous thromboembolism after treatment with Vitamin K antagonist in relation to the time since the index event. Methods Computerized searches in MEDLINE and EMBASE databases; reference checKs of pertinent articles; personal communication with colleagues to find randomized clinical trials and cohort studies in which patients with venous thromboembolism were treated with Vitamin K Antagonists. Per treatment arm, 2 reviewers independently extracted data on the number of recurrent events and the duration of follow-up per time period of 3 months. Results A total of 135 potentially eligible studies were identified. Of these, 18 studies could be included, comprising 25 treatment arms that could be analyzed. Treatment arms were divided into 3 groups based on treatment duration (short, medium, and long). For all 3 groups, the monthly incidence immediately after discontinuation of treatment was high and declined rapidly thereafter. The monthly incidence after 9 months seemed independent of the treatment duration. Conclusions There is a diminishing risK of recurrent venous thromboembolism over time and a stabilization after 9 months independent of the duration of the initial treatment with Vitamin K Antagonists. These findings have important implications for decision maKing about the optimal duration of treatment with Vitamin K Antagonists.
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Quality of life and the duration of treatment with Vitamin K Antagonists in patients with deep venous thrombosis
Thrombosis and haemostasis, 2003Co-Authors: Mirjam Locadia, Harry R. Büller, Mirjam A. G. Sprangers, Hanneke C. J. M. De Haes, M H PrinsAbstract:In cliIn clinical practice, decisions on the duration of treatment with Vitamin K Antagonists are usually based on the presence of per-sistent risK factors, the risK of bleeding and centre policy. Little is Known about the influence of patients’ experienced quality of life. The objectives of this study were: 1) to explore the course of quality of life in patients with venous thrombosis treated for 3 months versus patients treated for 6 months with Vitamin K Antagonists; 2) to investigate the factors that were associated with the duration of treatment with Vitamin K Antagonists. The study sample comprised patients participating in a multi-centre clinical trial. Quality of life was assessed at study entry, after 10-14 days, 3 and 6 months in 360 patients. Overall, no difIn clinical practice, decisions on the duration of treatment with Vitamin K Antagonists are usually based on the presence of per-sistent risK factors, the risK of bleeding and centre policy. Little is Known about the influence of patients’ experienced quality of life. The objectives of this study were: 1) to explore the course of quality of life in patients with venous thrombosis treated for 3 months versus patients treated for 6 months with Vitamin K Antagonists; 2) to investigate the factors that were associated with the duration of treatment with Vitamin K Antagonists. The study sample comprised patients participating in a multi-centre clinical trial. Quality of life was assessed at study entry, after 10-14 days, 3 and 6 months in 360 patients. Overall, no dif-Correspondence
Gregory Y.h. Lip - One of the best experts on this subject based on the ideXlab platform.
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real world setting comparison of nonVitamin K antagonist oral anticoagulants versus Vitamin K Antagonists for stroKe prevention in atrial fibrillation a systematic review and meta analysis
Stroke, 2017Co-Authors: George Ntaios, Vasileios Papavasileiou, Konstantinos Makaritsis, Konstantinos Vemmos, Patrik Michel, Gregory Y.h. LipAbstract:BacKground and Purpose— Evidence from the real-world setting complements evidence coming from randomized controlled trials. We aimed to summarize all available evidence from high-quality real-world observational studies about efficacy and safety of nonVitamin-K oral anticoagulants compared with Vitamin-K Antagonists in patients with atrial fibrillation. Methods— We searched PubMed and Web of Science until January 7, 2017 for observational nationwide or health insurance databases reporting matched or adjusted results comparing nonVitamin-K oral anticoagulants versus Vitamin-K Antagonists in patients with atrial fibrillation. Outcomes assessed included ischemic stroKe, ischemic stroKe or systemic embolism, any stroKe or systemic embolism, myocardial infarction, intracranial hemorrhage, major hemorrhage, gastrointestinal hemorrhage, and death. Results— In 28 included studies of dabigatran, rivaroxaban, and apixaban compared with Vitamin-K Antagonists, all 3 nonVitamin-K oral anticoagulants were associated with a large reduction of intracranial hemorrhage (apixaban hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.31–0.63; dabigatran HR, 0.42; 95% CI, 0.37–0.49; rivaroxaban HR, 0.64; 95% CI, 0.47–0.86); similar rates of ischemic stroKe and ischemic stroKe or systemic embolism (apixaban HR, 1.05; 95% CI, 0.75–1.19 and HR, 1.08; 95% CI, 0.95–1.22 / dabigatran HR, 0.96; 95% CI, 0.80–1.16 and HR, 1.17; 95% CI, 0.92–1.50 / rivaroxaban HR, 0.89; 95% CI, 0.76–1.04 and HR, 0.73; 95% CI, 0.52–1.04, respectively); apixaban and dabigatran with lower mortality (HR, 0.65; 95% CI, 0.56–0.75 and HR, 0.63; 95% CI, 0.53–0.75, respectively); apixaban with fewer gastrointestinal (HR, 0.63; 95% CI, 0.42–0.95) and major hemorrhages (HR, 0.55; 95% CI, 0.48–0.63); dabigatran and rivaroxaban with more gastrointestinal hemorrhages (HR, 1.20; 95% CI, 1.06–1.36 and HR, 1.24; 95% CI, 1.08–1.41, respectively); dabigatran and rivaroxaban with similar rate of myocardial infarction (HR, 0.96; 95% CI, 0.77–1.21 and HR, 1.02; 95% CI, 0.54–1.89, respectively). Conclusions— This meta-analysis confirms the main findings of the randomized controlled trials of dabigatran, rivaroxaban, and apixaban in the real-world setting and, hence, strengthens their validity.
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non Vitamin K oral anticoagulants versus Vitamin K Antagonists in the treatment of venous thromboembolic disease
Expert Opinion on Pharmacotherapy, 2016Co-Authors: Christos Voukalis, Gregory Y.h. Lip, Eduard ShantsilaAbstract:ABSTRACTIntroduction: Venous thromboembolism (VTE) is a major cause of morbidity and mortality in the western world. The approval of non-Vitamin K oral anticoagulants (NOACs) as antithrombotic alternatives to Vitamin K Antagonists (VKAs) has offered more treatment options to physicians for the prevention of VTE recurrence, fatal pulmonary embolism (PE) and long-term complications. Four NOACs (dabigatran, rivaroxaban, apixaban and edoxaban) that have been approved for the treatment of acute VTE following large phase III trials, where NOACs demonstrated similar efficacy and superior safety profile compared to VKAs.Areas covered: The purpose of this review article is to summarise current Knowledge of oral anticoagulation for the treatment of acute VTE and to compare NOACs with VKAs, highlighting the factors that might influence the decisions of physicians. Data for this article were obtained through a search of PubMed for trials comparing NOACs with VKAs in acute VTE setting and articles or analyses that int...
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the same tt2r2 score and quality of anticoagulation in atrial fibrillation a simple aid to decision maKing on who is suitable or not for Vitamin K Antagonists
Europace, 2015Co-Authors: Laurent Fauchier, Denis Angoulvant, Gregory Y.h. LipAbstract:This editorial refers to ‘Evaluation of SAMe-TT2R2 risK score for predicting the quality of anticoagulation control in a real-world cohort of patients with non-valvular atrial fibrillation on Vitamin-K Antagonists’ by M. R.R.-Y. Abumuaileq et al. , doi:10.1093/europace/euu353. Maintaining the therapeutic range in patients treated with Vitamin K Antagonists (VKAs) had always been challenging whilst the potential consequences of deviating from the optimal average time in therapeutic range(TTR) are deleterious in patients with atrial fibrillation (AF), given the risK for thromboembolic and bleeding events.1,2 Various clinical decision-maKing tools have been developed to help decision-maKing in the management of AF patients. In 2013, a new score—with the acronym SAMe-TT2R2—was proposed to help identify those patients who were liKely to have a propensity to poor INR control (as reflected by average time in the therapeutic range [TTR] 2).3 This score was derived from a trial cohort and thus independent validation in ‘real-world’ AF cohorts would be needed. In the current issue of EP-Europace , Abumaileq et al. 4 performed a retrospective analysis of a cohort of outpatients with non-valvular AF and found that SAMe-TT2R2 could indeed represented a useful clinical tool to identify a poor quality of anticoagulation control with VKAs. The predictive ability of SAMe-TT2R2 was acceptable for identifying low TTR and improved when integrated with other clinical characteristics. A strong relationship …
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efficacy and safety of Vitamin K Antagonists vKa for atrial fibrillation in non dialysis dependent chronic Kidney disease
PLOS ONE, 2014Co-Authors: Judith Kooiman, Nienke Van Rein, Bas Spaans, Koen A J Van Beers, Jonna R Bank, Wilke R Van De Peppel, Antonio Del Sol, Suzanne C Cannegieter, Ton J Rabelink, Gregory Y.h. LipAbstract:BacKground Essential information regarding efficacy and safety of Vitamin K-Antagonists (VKA) treatment for atrial fibrillation (AF) in non-dialysis dependent chronic Kidney disease (CKD) is still lacKing in current literature. The aim of our study was to compare the risKs of stroKe or transient ischemic attacK (TIA) and major bleeds between patients without CKD (eGFR >60 ml/min), and those with moderate (eGFR 30–60 ml/min), or severe non-dialysis dependent CKD (eGFR <30 ml/min).
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The Vitamin K Antagonists and their limitations
Handbook of Oral Anticoagulation, 2010Co-Authors: Chee W. Khoo, Gregory Y.h. LipAbstract:The Vitamin K Antagonists (VKAs) have been the mainstay of oral anticoagulant therapy for more than 50 years, warfarin being the VKA most commonly used worldwide. The longstanding popularity of the VKAs is largely based on their effectiveness in the prevention and treatment of venous thromboembolism (VTE), as well as the prevention of systemic embolism in patients who have mechanical heart valves or atrial fibrillation (AF).
B A Hutten - One of the best experts on this subject based on the ideXlab platform.
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duration of treatment with Vitamin K Antagonists in symptomatic venous thromboembolism
Cochrane Database of Systematic Reviews, 2014Co-Authors: Saskia Middeldorp, M H Prins, B A HuttenAbstract:BACKGROUND: Currently, the most frequently used secondary treatment for patients with venous thromboembolism is Vitamin K Antagonists targeted at an INR of 2.5 (range 2.0 to 3.0). However, based on the continuing risK of bleeding and uncertainty regarding the risK of recurrent venous thromboembolism, there is discussion on the proper duration of treatment with Vitamin K Antagonists for these patients. Recently, several studies were published in which the risK and benefits of different durations of oral anticoagulants were compared in patients with venous thromboembolism. OBJECTIVES: The objective of this review was to evaluate efficacy and safety of different durations of treatment with Vitamin K Antagonists in patients with symptomatic venous thromboembolism. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 3, 2005). The Specialised Register is constructed from electronic searches of MEDLINE (from inception to October 2005) and EMBASE (inception to October 2005) and through handsearching relevant journals. In addition, we also contacted colleagues for details of trials. The last searches were carried out on 11 October 2005. SELECTION CRITERIA: Randomized controlled clinical trials comparing different durations of treatment with Vitamin K Antagonists in patients with symptomatic venous thromboembolism. DATA COLLECTION AND ANALYSIS: Two reviewers (BH and MP) extracted the data and assessed the quality of the trials independently. MAIN RESULTS: Eight studies with a total of 2994 patients were included. A consistent reduction in the risK of recurrent events was observed during prolonged treatment with Vitamin K Antagonists (OR 0.18; 95% CI 0.13 to 0.26) independent of the period elapsed since the index thrombotic event. A 'rebound' phenomenon, i.e. an excess of recurrences shortly after cessation of the prolonged treatment was not observed (OR 1.24; 95% CI 0.91 to 1.69). In addition, a substantial increase in bleeding complications was found during the entire period after randomization (OR 2.62; 95% CI 1.48 to 4.61). AUTHORS' CONCLUSIONS: In conclusion, this meta-analysis shows that treatment with Vitamin K Antagonists reduces the risK of recurrent venous thromboembolism for as long as it is used. However, the absolute risK of recurrent venous thromboembolism declines over time, while the risK for major bleeding remains. Thus, the efficacy of Vitamin K antagonist administration decreases over time since the index event
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Duration of treatment with Vitamin K Antagonists in symptomatic venous thromboembolism.
The Cochrane database of systematic reviews, 2006Co-Authors: B A Hutten, M H PrinsAbstract:Currently, the most frequently used secondary treatment for patients with venous thromboembolism is Vitamin K Antagonists targeted at an INR of 2.5 (range 2.0 to 3.0). However, based on the continuing risK of bleeding and uncertainty regarding the risK of recurrent venous thromboembolism, there is discussion on the proper duration of treatment with Vitamin K Antagonists for these patients. Recently, several studies were published in which the risK and benefits of different durations of oral anticoagulants were compared in patients with venous thromboembolism. The objective of this review was to evaluate efficacy and safety of different durations of treatment with Vitamin K Antagonists in patients with symptomatic venous thromboembolism. The Cochrane Peripheral Vascular Diseases Group searched their Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library Issue 3, 2005). The Specialised Register is constructed from electronic searches of MEDLINE (from inception to October 2005) and EMBASE (inception to October 2005) and through handsearching relevant journals. In addition, we also contacted colleagues for details of trials. The last searches were carried out on 11 October 2005. Randomized controlled clinical trials comparing different durations of treatment with Vitamin K Antagonists in patients with symptomatic venous thromboembolism. Two reviewers (BH and MP) extracted the data and assessed the quality of the trials independently. Eight studies with a total of 2994 patients were included. A consistent reduction in the risK of recurrent events was observed during prolonged treatment with Vitamin K Antagonists (OR 0.18; 95% CI 0.13 to 0.26) independent of the period elapsed since the index thrombotic event. A 'rebound' phenomenon, i.e. an excess of recurrences shortly after cessation of the prolonged treatment was not observed (OR 1.24; 95% CI 0.91 to 1.69). In addition, a substantial increase in bleeding complications was found during the entire period after randomization (OR 2.62; 95% CI 1.48 to 4.61). In conclusion, this meta-analysis shows that treatment with Vitamin K Antagonists reduces the risK of recurrent venous thromboembolism for as long as it is used. However, the absolute risK of recurrent venous thromboembolism declines over time, while the risK for major bleeding remains. Thus, the efficacy of Vitamin K antagonist administration decreases over time since the index event.
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The relationship between adherence and quality of treatment with Vitamin K Antagonists
Journal of Thrombosis and Haemostasis, 2004Co-Authors: Mirjam Locadia, B A Hutten, Mirjam A. G. Sprangers, J. H. H. Van Geest-daalderop, M H PrinsAbstract:Objective To assess the relationship between adherence and quality of treatment with Vitamin K Antagonists. Methods Patients diagnosed with atrial fibrillation and treated with acenocoumarol were eligible. The percentage of time spent in the target range during the last three months was calculated using linear interpolation. Adherence was assessed with a self-report questionnaire. Results Forty patients who spent 100% (high-quality group) and 40 patients who spent less than 50% of time in the target range were approached for the study. Twenty-seven patients with high and 29 patients with low therapeutic quality returned the questionnaire. In the high-quality group, 88% of patients reported to have taKen all prescribed medication in the previous month, 96% reported to have been fully compliant in the previous weeK, and 76% reported to have taKen all their tablets on time in the previous weeK. These percentages were 82, 90, and 72, respectively in the low-quality group. Differences between the groups were not statistically significant. Conclusion The results indicate that adherence is not related to time spent in the therapeutic target range in older patients with atrial fibrillation treated with Vitamin K Antagonists.
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the incidence of recurrent venous thromboembolism after treatment with Vitamin K Antagonists in relation to time since first event a meta analysis
JAMA Internal Medicine, 2003Co-Authors: Carlo J Van Dongen, Roel Vink, Harry R. Büller, B A Hutten, M H PrinsAbstract:BacKground After a first episode of venous thromboembolism, patients are treated with Vitamin K (phytonadione) Antagonists. There are indications that the risK of recurrence after treatment with Vitamin K Antagonists decreases relative to the time since the first event. The aim of the present meta-analysis is to describe the risK of recurrent venous thromboembolism after treatment with Vitamin K antagonist in relation to the time since the index event. Methods Computerized searches in MEDLINE and EMBASE databases; reference checKs of pertinent articles; personal communication with colleagues to find randomized clinical trials and cohort studies in which patients with venous thromboembolism were treated with Vitamin K Antagonists. Per treatment arm, 2 reviewers independently extracted data on the number of recurrent events and the duration of follow-up per time period of 3 months. Results A total of 135 potentially eligible studies were identified. Of these, 18 studies could be included, comprising 25 treatment arms that could be analyzed. Treatment arms were divided into 3 groups based on treatment duration (short, medium, and long). For all 3 groups, the monthly incidence immediately after discontinuation of treatment was high and declined rapidly thereafter. The monthly incidence after 9 months seemed independent of the treatment duration. Conclusions There is a diminishing risK of recurrent venous thromboembolism over time and a stabilization after 9 months independent of the duration of the initial treatment with Vitamin K Antagonists. These findings have important implications for decision maKing about the optimal duration of treatment with Vitamin K Antagonists.
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Vitamin K Antagonists or low-molecular-weight heparin for the long term treatment of symptomatic venous thromboembolism.
The Cochrane database of systematic reviews, 2002Co-Authors: J.f. Van Der Heijden, B A Hutten, H R Büller, M H PrinsAbstract:People with venous thromboembolism are generally treated for five days with intravenous unfractionated heparin or subcutaneous low-molecular-weight heparin followed by three months of Vitamin K Antagonists treatment. Treatment with Vitamin K Antagonists requires regular laboratory measurements and some patients have contraindications for treatment. To evaluate the efficacy and safety of long-term treatment of venous thromboembolism with low-molecular-weight heparins compared to Vitamin K Antagonists. Searches of MEDLINE, EMBASE and ISI Web of Science, the Specialised Trials Register of the Cochrane Peripheral Vascular Disease Group and the Cochrane Controlled Trials Register were made and relevant journals were hand-searched. Additional trials were sought through communication with colleagues and pharmaceutical companies. Two reviewers evaluated studies independently for methodological quality. Two reviewers extracted data independently. Primary analysis concerned all trial participants during the period of randomized treatment. Separate analyses were performed for category I and category II studies; i.e. studies using similar treatments initially in both study arms, and those that did not; and the different periods of follow-up. All seven studies fulfilling our criteria combined, a statistically non-significant reduction in the risK of recurrent venous thromboembolism favoring low-molecular-weight heparin treatment (OR 0.70; 95% CI [0.42, 1.16]) was found. Analysis of pooled data for category I studies showed a non-significant reduction in the risK of recurrent venous thromboembolism favoring low-molecular-weight heparin treatment (OR 0.75; 95% CI [0.40, 1.39]). Omitting a potentially-confounded study, a statistically non-significant reduction in the risK of recurrent venous thromboembolism favoring Vitamin K antagonist treatment remained (OR 1.95; 95% CI [0.74, 5.19]). All studies combined, the difference in bleeding significantly favored treatment with low-molecular-weight heparin (OR 0.38; 95% CI [0.15, 0.94]), however, considering only category I studies a non-significant trend favoring low-molecular-weight heparin remained (OR 0.80; 95% CI [0.21, 3.00]). No difference was observed in mortality (OR 1.13; 95% CI [0.47, 2.69]). Low-molecular-weight heparins are possibly as effective as Vitamin K Antagonists in preventing symptomatic venous thromboembolism after an episode of symptomatic deep venous thrombosis, but are much more expensive. Treatment with low-molecular-weight heparin is significantly safer than treatment with Vitamin K Antagonists and is possibly a safe alternative in some patients; especially those in geographically inaccessible places, reluctant to visit the thrombosis service regularly, or with contraindications to Vitamin K Antagonists. However, treatment with Vitamin K Antagonists remains the treatment of choice for the majority of patients.
Leon J Schurgers - One of the best experts on this subject based on the ideXlab platform.
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Vitamin K Antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype
PLOS ONE, 2012Co-Authors: Leon J Schurgers, Martijn L Chatrou, Ivo A Joosen, Eduard M Laufer, Marjolein Herfs, Mark H M Winkens, Ralf Westenfeld, Verena Veulemans, Thilo Krueger, Catherine M ShanahanAbstract:BacKground Vitamin K-Antagonists (VKA) are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risK. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risK factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE−/− model of atherosclerosis. Methodology/Principal Findings A total of 266 patients (133 VKA users and 133 gender and Framingham RisK Score matched non-VKA users) underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD). VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE−/− mice (10 weeKs) received a Western type diet (WTD) for 12 weeKs, after which mice were fed a WTD supplemented with Vitamin K1 (VK1, 1.5 mg/g) or Vitamin K1 and warfarin (VK1W 1.5 mg/g & 3.0 mg/g) for 1 or 4 weeKs, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden. Conclusions/Significance VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE−/− mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the Vitamin K cycle.
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Vitamin K Antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype
PLOS ONE, 2012Co-Authors: Leon J Schurgers, Martijn L Chatrou, Ivo A Joosen, Eduard M Laufer, Marjolein Herfs, Mark H M Winkens, Ralf Westenfeld, Verena Veulemans, Thilo Krueger, Catherine M ShanahanAbstract:BacKground Vitamin K-Antagonists (VKA) are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risK. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risK factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE−/− model of atherosclerosis. Methodology/Principal Findings A total of 266 patients (133 VKA users and 133 gender and Framingham RisK Score matched non-VKA users) underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD). VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE−/− mice (10 weeKs) received a Western type diet (WTD) for 12 weeKs, after which mice were fed a WTD supplemented with Vitamin K1 (VK1, 1.5 mg/g) or Vitamin K1 and warfarin (VK1W 1.5 mg/g & 3.0 mg/g) for 1 or 4 weeKs, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden. Conclusions/Significance VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE−/− mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the Vitamin K cycle.
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vascular calcification the price to pay for anticoagulation therapy with Vitamin K Antagonists
Blood Reviews, 2012Co-Authors: Martijn L Chatrou, Kristien Winckers, Tilman M Hackeng, Chris P M Reutelingsperger, Leon J SchurgersAbstract:Vitamin K-Antagonists (VKA) are the most widely used anti-thrombotic drugs with substantial efficacy in reducing risK of arterial and venous thrombosis. Several lines of evidence indicate, however, that VKA inhibit not only post-translational activation of Vitamin K-dependent coagulation factors but also synthesis of functional extra-hepatic Vitamin K-dependent proteins thereby eliciting undesired side-effects. Vascular calcification is one of the recently revealed side-effects of VKA. Vascular calcification is an actively regulated process involving vascular cells and a number of Vitamin K-dependent proteins. Mechanistic understanding of vascular calcification is essential to improve VKA-based treatments of both thrombotic disorders and atherosclerosis. This review addresses Vitamin K-cycle and Vitamin K-dependent processes of vascular calcification that are affected by VKA. We conclude that there is a growing need for better understanding of the effects of anticoagulants on vascular calcification and atherosclerosis.
Catherine M Shanahan - One of the best experts on this subject based on the ideXlab platform.
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Vitamin K Antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype
PLOS ONE, 2012Co-Authors: Leon J Schurgers, Martijn L Chatrou, Ivo A Joosen, Eduard M Laufer, Marjolein Herfs, Mark H M Winkens, Ralf Westenfeld, Verena Veulemans, Thilo Krueger, Catherine M ShanahanAbstract:BacKground Vitamin K-Antagonists (VKA) are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risK. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risK factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE−/− model of atherosclerosis. Methodology/Principal Findings A total of 266 patients (133 VKA users and 133 gender and Framingham RisK Score matched non-VKA users) underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD). VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE−/− mice (10 weeKs) received a Western type diet (WTD) for 12 weeKs, after which mice were fed a WTD supplemented with Vitamin K1 (VK1, 1.5 mg/g) or Vitamin K1 and warfarin (VK1W 1.5 mg/g & 3.0 mg/g) for 1 or 4 weeKs, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden. Conclusions/Significance VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE−/− mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the Vitamin K cycle.
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Vitamin K Antagonists accelerate atherosclerotic calcification and induce a vulnerable plaque phenotype
PLOS ONE, 2012Co-Authors: Leon J Schurgers, Martijn L Chatrou, Ivo A Joosen, Eduard M Laufer, Marjolein Herfs, Mark H M Winkens, Ralf Westenfeld, Verena Veulemans, Thilo Krueger, Catherine M ShanahanAbstract:BacKground Vitamin K-Antagonists (VKA) are treatment of choice and standard care for patients with venous thrombosis and thromboembolic risK. In experimental animal models as well as humans, VKA have been shown to promote medial elastocalcinosis. As vascular calcification is considered an independent risK factor for plaque instability, we here investigated the effect of VKA on coronary calcification in patients and on calcification of atherosclerotic plaques in the ApoE−/− model of atherosclerosis. Methodology/Principal Findings A total of 266 patients (133 VKA users and 133 gender and Framingham RisK Score matched non-VKA users) underwent 64-slice MDCT to assess the degree of coronary artery disease (CAD). VKA-users developed significantly more calcified coronary plaques as compared to non-VKA users. ApoE−/− mice (10 weeKs) received a Western type diet (WTD) for 12 weeKs, after which mice were fed a WTD supplemented with Vitamin K1 (VK1, 1.5 mg/g) or Vitamin K1 and warfarin (VK1W 1.5 mg/g & 3.0 mg/g) for 1 or 4 weeKs, after which mice were sacrificed. Warfarin significantly increased frequency and extent of vascular calcification. Also, plaque calcification comprised microcalcification of the intimal layer. Furthermore, warfarin treatment decreased plaque expression of calcification regulatory protein carboxylated matrix Gla-protein, increased apoptosis and, surprisingly outward plaque remodeling, without affecting overall plaque burden. Conclusions/Significance VKA use is associated with coronary artery plaque calcification in patients with suspected CAD and causes changes in plaque morphology with features of plaque vulnerability in ApoE−/− mice. Our findings underscore the need for alternative anticoagulants that do not interfere with the Vitamin K cycle.
