Use Of Target-specific Oral Anticoagulants Research Articles

Target-specific Oral Anticoagulants in the Emergency Department

BackgroundEmergency physicians make treatment decisions in patients who present to the emergency department (ED) with acute venous thromboembolism (VTE). They also encounter patients on target-specific oral anticoagulants (TSOACs) who require urgent intervention. New approvals and increasing prescriptions for TSOACs (e.g., apixaban, dabigatran, edoxaban, and rivaroxaban) for the management of several thromboembolic disorders warrant an evaluation of the impact of these agents in the ED setting. Objective of the ReviewThis review discusses the use of TSOACs in the ED for the treatment of acute VTE, and highlights strategies for the management of patients on TSOACs who present to the ED with other complications, such as bleeding complications or requiring emergency surgery. DiscussionApixaban, dabigatran, edoxaban, and rivaroxaban have been approved for the treatment of acute VTE. We discuss the impact of this on ED management of TSOAC-naïve patients and highlight results with TSOACs in high-risk subgroups including the elderly and those with prior VTE or active cancer. This review also discusses management strategies for patients on TSOACs. For emergency physicians, strategies for the management of bleeding, approaches to patient care when emergency surgery is needed, laboratory assays for measuring plasma concentrations of TSOACs, and drug–drug interactions are of special importance. ConclusionsFamiliarity with TSOACs will better position emergency physicians to provide state-of-the art care to their patients with VTE and help them manage potentially complicated circumstances related to the chronic use of these drugs.

Dosing of Target-Specific Oral Anticoagulants in Special Populations.

To review current literature for target-specific oral anticoagulants (TSOACs) and provide critical analysis for dosing recommendations in special population groups. A literature search was conducted in Medline (1996 to April week 2 2015) and Embase (1980 to 2015 week 16) using key terms dabigatran, rivaroxaban, apixaban, edoxaban, kidney diseases, liver diseases, elderly, obesity, and special populations. Randomized controlled trials in English assessing efficacy and safety of TSOACs in healthy adults and special populations were selected for analysis. Phase 3 trials for TSOACs predominately excluded patients with severe renal impairment or active liver disease. There were no exclusion criteria based on age, body weight or body mass index. Additional conclusions were made in special populations, including those with renal or liver impairment and obese and elderly patients, based on secondary analyses, pharmacokinetic, and pharmacodynamic studies. Pharmacokinetic and pharmacodynamic changes associated special populations may alter clinical decision with regard to drug selection and dosing. It is valuable to understand the rationale for labeled dosing recommendations in nonvalvular atrial fibrillation and venous thromboembolism treatment and prevention, particularly in patients that fall into special population groups. Furthermore, the use of TSOACs is likely to increase as clinicians gain experience with these agents and additional TSOACs and indications are approved.

Evaluation of prescribing and patient use of target-specific oral anticoagulants in the outpatient setting.

Pharmacist-managed anticoagulation programmes have been shown to improve appropriate use of warfarin, but few programmes have included the new target-specific oral anticoagulants (TSOACs) in their protocols. A greater understanding of TSOAC prescribing, monitoring and administration is needed to identify common errors in the current outpatient practice. The objective of this study is to assess the rate of errors related to prescribing, baseline monitoring and patient administration of TSOACs. A retrospective chart review was conducted to identify patients on TSOAC therapy in each of four outpatient practice sites. Data were abstracted to include TSOAC indication, dosage and frequency prescribed, pertinent past medical history, and laboratory monitoring obtained at the time of TSOAC initiation. In addition, patients were contacted by telephone to assess TSOAC adherence, storage, administration and incidence of adverse events. A total of 395 patients were included in the evaluation. Prescribers did not obtain baseline laboratory values within 1week before or after the time of TSOAC initiation for a majority of study patients. At the time of TSOAC initiation, two patients had abnormally elevated alanine aminotransferase, six had elevated total bilirubin, and 43 had low haemoglobin. A majority (61%) of study patients were prescribed an appropriate TSOAC dose based upon their indication and renal function; however, dosing accuracy could not be determined for all patients as baseline serum creatinine was not obtained by prescribers for 148 patients (37%) at the time of prescribing. TSOACs were dosed inappropriately according to baseline serum creatinine in six patients, and two patients receiving treatment for venous thromboembolism were maintained on a high dose of rivaroxaban for an inappropriate duration. A total of 157 (40%) patients were available by phone and agreed to answer questions regarding their current TSOAC use. Twenty-four patients (23%) reported taking rivaroxaban inappropriately without food, and six patients (14%) endorsed inappropriate storage of dabigatran. Ten patients (6%) reported missing at least one TSOAC dose per week, and 25 (16%) described minor bleeding with their TSOAC. Inappropriate prescribing, monitoring and administration of TSOACs occurred frequently in patients not formally enrolled in an anticoagulation monitoring programme. These results indicate a need for more thorough patient education at the time of TSOAC initiation, as well as improved prescriber education regarding recommended TSOAC dosing and monitoring.

Analysis of anticoagulant prescribing in non-valvular atrial fibrillation and development of a clinical tool for guiding anticoagulant selection.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States. Traditionally, warfarin has been used to prevent the occurrence of stroke in intermediate-to-high risk patients. Target-specific oral anticoagulants (TSOACs) have become a favorable alternative; however, recommendations for differentiating between the available TSOACs were lacking within the 2012 CHEST guidelines. The objective of this retrospective, observational study was to identify current anticoagulation prescribing habits in patients admitted with new-onset AF, and evaluate the appropriateness of discharge therapy based on national guidelines. Additionally, a practice guideline was created for use at our institution to stratify appropriate use of TSOACs. Patients were included if they were at least 18 years old and were admitted with a primary diagnosis of new-onset, non-valvular AF between July 1, 2012 and June 30, 2013. CHADS2, CHA2DS2VASc, and HAS-BLED scores were calculated based on patient data. Between July 2012 and June 2013, 143 patients were included in the study. The average CHADS2 score was 1.7, the average CHA2DS2VASc score was 3.0, and the average HAS-BLED score was 2.4. The use of no antithrombotics decreased as the CHA2DS2VASc score increased, aspirin use stayed consistent across risk groups, warfarin use increased as the CHA2DS2VASc score increased, and TSOAC use decreased with increasing CHA2DS2VASc score. A total of 34% of study patients were prescribed inappropriate treatment upon discharge, based on national guidelines. This study demonstrated that patients admitted to our hospital were prescribed appropriate therapy the majority of the time; however, 34% were prescribed inadequate antithrombotic therapy compared to current practice guidelines given their CHA2DS2VASc score. The development of an institution-specific guideline stratifying appropriate use of anticoagulation in this population may increase adherence to national guideline recommendations.

Use Patterns and Unlabeled Uses of Target-Specific Oral Anticoagulants: A Single-Center Experience.

Background: Target-specific oral anticoagulants (TSOAs) have advantages and disadvantages over warfarin, and they differ by indication, dosage adjustment, and drug interactions. Objective: The purpose of this retrospective cohort study is to determine use patterns and unlabeled uses of TSOAs. Methods: From July 1, 2012, to April 30, 2014, orders for warfarin, dabigatran, rivaroxaban, or apixaban in a tertiary medical center were included. Electronic medical records were reviewed to collect information regarding characteristics of the patients receiving these medications. Unlabeled use was defined as an indication or dose not approved by the US Food and Drug Administration. The percentage of orders for each study drug per month and the percentage of orders for each TSOA that contained an unlabeled use were calculated. Results: Of a total of 869 orders, 140 (16.1%) were for TSOAs (13 dabigatran, 97 rivaroxaban, and 30 apixaban orders). Compared with the first 4 months of the study period, the monthly percentage of orders for a TSOA increased by 2.5-fold in the last 4 months. Of the 3 TSOAs, only orders for dabigatran decreased (5.6% in July 2012 vs 0% in April 2014). Of the 140 TSOA orders, 28 (20.0 %) were unlabeled uses (3 unlabeled indications and 25 unlabeled dose), which included 16 unlabeled renally adjusted doses. The percentage of unlabeled uses did not significantly differ by TSOA. Conclusion: The use of TSOAs has increased and unlabeled uses are common. These data provide opportunities for quality improvement in the use of TSOA in clinical practice.

New developments in pediatric venous thromboembolism and anticoagulation, including the target-specific oral anticoagulants.

Pediatric venous thromboembolism (VTE) can affect children of all ages, requiring considerable pharmacologic intervention and is often associated with significant morbidity. Current research efforts are directed toward the development of risk-stratified VTE prevention strategies employing pharmacologic thromboprophylaxis, the optimization of conventional anticoagulation, and the investigation of the safety and efficacy of target-specific oral anticoagulants (TSOACs) in children. Recent research has considerably improved the understanding of risk factors of hospital-acquired VTE and how these factors may be employed in risk-stratified paradigms for VTE prevention in children. Additional insight has been gained in the optimization of conventional anticoagulants in special populations such as neonates and children with inflammatory conditions, and in improving the overall safety and compliance with periprocedural anticoagulation and the use of home International Normalized Ratio monitoring. Furthermore, the use of TSOACs has been described in children and is the focus of numerous ongoing clinical trials that are evaluating the safety and efficacy of these agents in children with VTE. Identification of hospital-acquired VTE risk factors may inform pediatric VTE prevention strategies. Although initial use of TSOACs may be promising, investigation of safety and efficacy in children is still underway.

Role of novel anticoagulants for patients with mechanical heart valves.

The introduction of the target-specific oral anticoagulants (TSOACs) has led to a major shift in the management of patients at risk for thrombosis. The landscape continues to evolve as the evidence regarding their efficacy and safety in various clinical situations emerges. Antithrombotic therapy for thromboprophylaxis in patients with mechanical heart valves is challenging. To date, the RE-ALIGN trial comparing dabigatran etexilate to warfarin is the only randomized controlled study in this patient population. The higher risk of thromboembolic and bleeding events in the group of patients who received dabigatran compared with warfarin reinforced current guidelines recommending against the use of TSOACs in patients with mechanical heart valves. However, additional studies are needed to find suitable alternatives to vitamin K antagonists in this unique patient population.

Practical aspects of new oral anticoagulant use in atrial fibrillation

Dabigatran, a direct thrombin inhibitor and 2 factor Xa inhibitors, rivaroxaban and apixaban, are target-specific oral anticoagulants (TSOACs) approved for prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation (AF). Published data suggest that all 3 agents are at least as efficacious as dose‑adjusted warfarin in stroke prevention. Because of their greater specificity, rapid onset of action, and predictable pharmacokinetics, TSOACs have some advantages over vitamin K antagonists, which facilitates their use in clinical practice. The current review addresses the practical questions relating to the use of TSOACs in AF patients based on the available data and personal experience. We discuss topics such as patient selection, renal impairment, drug interactions, switching between anticoagulants, laboratory monitoring, and the risk of bleeding along with its management. We will focus on the aspects of the optimization of treatment with TSOACs in stroke prevention. The understanding of these practical issues by clinicians and patients is of key importance for the safe and effective use of TSOACs in everyday practice.

Novel thrombin and factor Xa inhibitors

Warfarin has been the sole oral anticoagulant used in the management of thromboembolic disorders for over 60 years. Target-specific oral anticoagulants (TSOAs) have recently emerged as alternatives to warfarin, because they do not require laboratory monitoring. Nevertheless, with the rising use of TSOAs, there is growing concern among clinicians regarding management of bleeding in patients taking them. Unlike warfarin, there is no antidote or reversal agent for TSOAs. This review summarizes recent developments and attempts to provide a systematic approach to patients on TSOAs presenting with bleeding complications. Currently, data involving clinical management of TSOAs are limited and primarily based on ex-vivo or animal models using hemostatic agents with uncertain implications in bleeding patients. There is a pressing need for randomized clinical trials evaluating the safety and efficacy of hemostatic agents. Without evidence-based guidelines for TSOA management, appropriate patient care requires an understanding of TSOA pharmacology, their effect on coagulation tests and, hence, a correct interpretation of test results, as well as a systematic approach to bleeding complications.