scholarly journals Clinical and pharmacological properties of new oral anticoagulants for the prevention of cerebral thromboembolism: Factor Xa and thrombin inhibitors

2012 ◽  
Vol 02 (01) ◽  
pp. 7-14 ◽  
Author(s):  
Yaroslav Winter ◽  
Richard Dodel ◽  
Alexei Korchounov ◽  
Martin Grond ◽  
Wolfgang H. Oertel ◽  
...  
Keyword(s):  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Pharmacological Properties

Old and new anticoagulants

2011 ◽  
Vol 31 (01) ◽  
pp. 21-27 ◽  
Author(s):  
U. Harbrecht
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Clotting Factor ◽  
Direct Thrombin Inhibitors ◽  
Self Monitoring ◽  
New Anticoagulants ◽  
Gastrointestinal Side Effects

SummaryVitamin-K-antagonists (VKA) and heparins have been complementary anticoagulants for prevention and treatment of thrombosis for almost 70 years. In contrast to heparins, VKA have not been modified pharmacologically, however treatment surveillance has improved by introducing INR and self-monitoring/management. Disclosure of the molecular basis of interaction with VKORC1, the target enzyme of VKA, has helped to better understand coumarin sensitivity and resistance. New oral anticoagulants have now been approved and stimulated expectations in patients and physicians to get rid of the burdening frequent controls of VKA without loss of efficacy and safety.This review will summarize the development and profile of the new substances. Main difference compared to VKA is their direct mode of action against one clotting factor which is factor IIa in dabigatran and factor Xa in rivaroxaban and other “xabanes” currently under intensive investigation. Half lifes of the new anticoagulants are much shorter than that of the mainly used coumarins (phenprocoumon, warfarin), making “anticoagulation bridging” unnecessary before surgery. Therapeutic width of direct thrombin inhibitors and factor Xa inhibitors is broader and they are given at fixed doses. Clinical studies in thromboprophylaxis, thromboembolism and atrial fibrillation indicate at least non-inferiority or even superior efficacy compared with enoxaparin and VKA at comparable safety outcomes. Limitations of the new substances may arise from gastrointestinal side effects, mode of metabolism and route of elimination. Specific antidots are not available for none of them.Undoubtedly, the new oral anticoagulants are very promising. But, although thousands of study patients already have been treated, there are questions to be answered such as treatment adherence in absence of monitoring, safety and efficacy in risk patients, dosage adjustment and interactions with other drugs, before conclusions can be drawn towards their potential to replace VKA.

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.

Heparin induced thrombocytopenia

2015 ◽  
Vol 35 (04) ◽  
pp. 372-375 ◽  
Author(s):  
N. A. Viniou ◽  
P. Diamantopoulos ◽  
J. Barbetseas ◽  
E. A. Sanidas
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Treatment Options ◽  
Factor Xa ◽  
Additional Treatment ◽  
Thrombin Inhibitors ◽  
Factor Xa Inhibitors ◽  
Clinical Aspects ◽  
Heparin Induced Thrombocytopenia

SummaryHeparin induced thrombocytopenia (HIT) is a prothrombotic syndrome initiated by platelet-activating auto-antibodies with potentially devastating complications. Once the diagnosis of HIT is suspected, discontinuation of heparin and treatment with an alternative anticoagulant are mandatory. While established drugs for HIT are no longer available, parenteral factor Xa inhibitors, thrombin inhibitors and perhaps the direct oral anticoagulants provide additional treatment options. The aim of this review was to highlight the current clinical aspects regarding HIT focusing on the role of novel medications.

Spotlight on real-world evidence for the treatment of DVT: XALIA

2016 ◽  
Vol 116 (S 02) ◽  
pp. S41-S49 ◽  
Author(s):  
Alexander Turpie ◽  
Walter Ageno
Keyword(s):  
Venous Thromboembolism ◽  
Real World ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
Standard Of Care ◽  
Thrombin Inhibitors ◽  
Direct Thrombin Inhibitors ◽  
Vein Thrombosis ◽  
Real World Evidence ◽  
Recurrent Vte

SummaryVenous thromboembolism (VTE), comprising both deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a serious and common cardiovascular disease associated with the risk of chronic complications, recurrent VTE events and even death. The treatment landscape has, in recent years, seen a paradigm shift from the use of traditional anticoagulants (low-molecular-weight heparin [LMWH] overlapping with and followed by a vitamin K antagonist [VKA]) to non-VKA oral anticoagulants (NOACs). This class of agents, encompassing direct factor Xa inhibitors and direct thrombin inhibitors have shown non-inferior efficacy and better safety to standard of care in randomised controlled trials (RCTs). The direct, oral factor Xa inhibitor rivaroxaban was the first to be approved for treatment of acute DVT and PE and secondary prevention of recurrent VTE events based on data from EINSTEIN DVT and EINSTEIN PE, respectively. Real-world evidence now helps to further support data from RCTs, and also bridges the gap for physicians regarding any areas of clinical uncertainty that may not be addressed by RCTs. XA inhibition with rivaroxaban for Long-term and Initial Anticoagulation in venous thromboembolism (XALIA) was the first large, prospective, observational, real-world study that has investigated the safety and effectiveness profile of rivaroxaban in patients with DVT and PE associated with DVT in routine clinical practice. This article will present the key clinical outcomes from this important global non-interventional study, and will discuss remaining questions to be addressed in Phase IV studies.

scholarly journals The Reversal of Bleeding Caused by New Oral Anticoagulants (NOACs): A Systematic Review and Meta-Analysis

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 117S-126S ◽  
Author(s):  
Sariya Udayachalerm ◽  
Sasivimol Rattanasiri ◽  
Teeranan Angkananard ◽  
John Attia ◽  
Nakarin Sansanayudh ◽  
...  
Keyword(s):  
Case Reports ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitor ◽  
Aggregated Data ◽  
Reversal Agents ◽  
Death Studies ◽  
Risk Of Death

New oral anticoagulants (NOACs; ie, direct thrombin inhibitor [DTI] and factor Xa [FXa] inhibitors) were used as alternatives to warfarin. Specific antidotes (idarucizumab for dabigatran and andexanet alfa for FXa inhibitors) and hemostatic reversal agents were used for lowering bleeding, but their efficacies were still uncertain. The objectives of this study were to estimate and compare the efficacy of NOAC antidotes on bleeding reversal and death. Studies were identified from MEDLINE and Scopus databases until May 2018. Case reports/series and cohorts were selected if they assessed reversal or death rates. Data were independently extracted by 2 reviewers. Individual patient data and aggregated data of outcomes were extracted from case reports/series and cohorts. Binary regression was used to estimate outcome rates, risk ratio (RR) along with 95% confidence interval (CI). Interventions were NOACs and reversal agents (ie, DTI-specific, DTI-standard, FXa-specific, and FXa-standard). Among 220 patients of 93 case reports/series, reversal rates were 95.9%, 77.6%, and 71.5% for DTI-specific, FXa-standard, and DTI-standard. Pooled RRs for DTI-specific and FXa-standard versus DTI-standard, respectively, were 1.34 (CI: 1.13-1.60) and 1.09 (CI: 0.84-1.40). Death rate was 0.18 (CI: 0.06-0.57) times lower in DTI-specific versus DTI-standard. For pooling 10 subcohorts, pooled RRs were 1.08 (CI: 1.00-1.16), 1.29 (CI: 1.20-1.39), and 1.13 (CI: 1.01-1.25) for DTI-specific, FXa-specific, and FXa-standard versus DTI-standard. In conclusion, specific reversal agents might be useful for reversal of bleeding and lowering the risk of death than standard reversal agents. Our findings were based on case reports/series and selected cohorts, further comparative studies are thus needed.

Evaluation of Assay Performance Monitoring the New Oral Anticoagulants Rivaroxaban and Dabigatran

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3424-3424
Author(s):  
Lieselotte Wagner ◽  
Martina Leitner ◽  
Viktoria Kaufmann ◽  
Jutta Mager
Keyword(s):  
Calibration Curve ◽  
Oral Anticoagulants ◽  
New Oral Anticoagulants ◽  
Thrombin Inhibitors ◽  
Thrombin Inhibitor ◽  
Good Precision ◽  
Thrombin Time ◽  
Target Value ◽  
Calibration Curves ◽  
High Range

Abstract Abstract 3424 Introduction: Dabigatran etexilate is a new orally direct thrombin inhibitor and rivaroxaban is a new oral direct Factor Xa (FXa) inhibitor. The increasing use of the new oral anticoagulants administered for prevention of VTE in patients after orthopedic surgery creates the need of their measurement in the clinical routine. A modified thrombin time based assay can be used for measurement of thrombin inhibitors like dabigatran and the direct Xa inhibitor rivaroxaban can be measured with a chromogenic anti-Xa assay. The aim of this study was to evaluate the performance of the two assays on coagulation analyzers using lyophilized calibrators and controls. Method: The assay for dabigatran measurement is a clotting assay based on the inhibition of a constant and defined concentration of thrombin. Clotting times measured are directly related to thrombin inhibitor concentrations. Calibration of the assay is performed using the lyophilized calibrators with assigned dabigatran values. Lyophilized controls in two ranges with assigned values for dabigatran are measured to calculate recovery and precision. A one stage chromogenic assay for the determination of Xa inhibitor activity in human citrated plasma is used for rivaroxaban measurement. The assay is based on the inhibition of activated factor × (FXa) by the direct Xa inhibitor rivaroxaban as measured by a chromogenic FXa substrate. Lyophilzed calibrators with assigned rivaroxaban values are used for assay calibration. Controls in 3 ranges are measured to calculate recovery and precision. Both assays are performed automated using the coagulation analyzers Ceveron alpha, Coasys Plus C and STA Compact with adapted pipetting schemes for the two anticoagulants on each analyzer. Results: For dabigatran measurement calibration curves in the range of 0–500ng/mL were made on each analyzer and curves with R2=1.0±0.1 were obtained on all analyzers. The recovery of control was ± 10% of target value for all controls on each analyzer. Precission data of the assay are summarized below: For rivaroxaban calibration curves in low range 0–150ng/mL and high range 0–500ng/mL were made using two adjusted analyzer settings. Calibration curves with R2=1.0±0.1 were obtained for rivaroxaban in the range of 0–150ng/mL, as well as for the range of 0–500ng/mL on all analyzers. The recovery of control was ± 10% of target value on all analyzers and precision was very good with intra-assay variations between 0.9%-4.2% and inter-assay variations between 1.8–4.9%. The detection limit for rivaroxaban was 10ng/mL using low range calibration curve and 25ng/mL using high range calibration curve. Conclusions: Our data demonstrate that the diluted thrombin time assay is suitable for mmeasurement of dabigatran and the chromogenic anti-Xa assay is suitable for measurement of rivaroxaban if lyophilized calibrators are used for assay calibration. Optimised pipetting schemes have to be validated for each of the analyzers used in order to obtain results with good precision. Disclosures: No relevant conflicts of interest to declare.

New oral anticoagulants in development

2010 ◽  
Vol 103 (01) ◽  
pp. 62-70 ◽  
Author(s):  
Jeffrey Weitz
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Factor Xa ◽  
New Oral Anticoagulants ◽  
Dietary Vitamin ◽  
Multiple Drug ◽  
Coagulation Monitoring ◽  
Advanced Stages

SummaryAlthough currently available anticoagulants are effective for the prevention and treatment of thromboembolic disorders, they have several drawbacks. Low-molecular-weight heparins and fondaparinux produce a predictable level of anticoagulation that obviates the need for coagulation monitoring, but they must be given parenterally, which renders them inconvenient for long-term use. Vitamin K antagonists, such as warfarin, are administered orally, but produce a variable anticoagulant response because genetic polymorphisms, dietary vitamin K intake and multiple drug-drug interactions affect their metabolism. Consequently, coagulation monitoring and frequent dose adjustments are needed to ensure that a therapeutic level of anticoagulation is achieved. This is burdensome for patients and physicians, and costly for the healthcare system. These limitations have prompted the development of new oral anticoagulants that target thrombin or factor Xa and can be given in fixed doses without coagulation monitoring. This paper focuses on the new oral anticoagulants in the most advanced stages of development.

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