- Liquid chromatographic methods for the determination of direct oral anticoagulant drugs in biological samples: A critical review. [Review]
- ACAnal Chim Acta 2019 Oct 17; 1076:18-31
- Direct oral anticoagulants (DOACs) are first-line drugs used for the treatment of venous thromboembolism and prevention of stroke in patients with atrial fibrillation. These drugs do not require the …
Direct oral anticoagulants (DOACs) are first-line drugs used for the treatment of venous thromboembolism and prevention of stroke in patients with atrial fibrillation. These drugs do not require the regular biochemical monitoring that is mandatory for warfarin, and they exhibit shorter half-lives and have a faster onset of action. Since recent real-world studies evidence a higher prevalence of adverse side effects than what was anticipated in clinical trials, monitoring the plasma concentrations of DOACs is being used to personalize their pharmacotherapy, in accordance to the characteristics of the patient, and to evaluate the adherence to therapy. In order to fulfill the aforementioned clinical unmet needs, there are specific coagulation assays that indirectly assess the plasma concentrations of DOACs. Nevertheless, these assays are not sufficiently accurate or sensitive. For this reason, liquid chromatography techniques coupled to mass spectrometry detection, are considered the gold standard method to accurately determine plasma concentrations of DOACs. Therefore, the present paper provides the first comprehensive review of the current analytical methods that were developed and validated for the quantitative determination of apixaban, dabigatran, rivaroxaban and/or edoxaban and their main metabolites in biological samples. The chromatographic methods will be particularly highlighted and an emphasis will be placed on the major difficulties faced during optimization and development steps. In addition, the physicochemical, pharmacokinetic and pharmacodynamic characteristics of each drug will be critically related to chromatographic conditions. Their influence on the pre-treatment procedures and storage conditions of DOACs will be examined, suggesting strategies that should be applied to accurately quantify DOACs in biological samples.
- Oral anticoagulants in atrial fibrillation with valvular heart disease and bioprosthetic heart valves. [Journal Article]
- HHeart 2019 Jun 14
- CONCLUSIONS: NOACs performed better than warfarin for a reduction in SSE, MI and ICH in patients with VHD. Individually NOACs performed similarly to each other except for an increased risk of ICH and major bleeding with rivaroxaban and a reduced risk of major bleeding with edoxaban 30 mg. In patients with a BPHV, results with NOACs seem similar to those with warfarin and this needs to be further explored in larger studies.
- Cost effectiveness analysis of direct oral anticoagulant (DOAC) versus dalteparin for the treatment of cancer associated thrombosis (CAT) in the United States. [Journal Article]
- TRThromb Res 2019 May 16; 180:37-42
- CONCLUSIONS: Rivaroxaban or edoxaban as compared to dalteparin is cost saving from a payer's perspective for the treatment of CAT. Professional organizations and healthcare systems may want to consider this analysis in future practice recommendations.
- Sustained safe and effective anticoagulation using Edoxaban via percutaneous endoscopic gastrostomy. [Case Reports]
- EHESC Heart Fail 2019 Jun 11
- Extensive data support the safety of direct oral anticoagulants compared with vitamin K antagonists in patients with non-valvular atrial fibrillation, leading to a significantly increase in the use o…
Extensive data support the safety of direct oral anticoagulants compared with vitamin K antagonists in patients with non-valvular atrial fibrillation, leading to a significantly increase in the use of these compounds in clinical practice. However, there is no compelling evidence supporting the use of direct oral anticoagulant in individuals who are intubated or have a percutaneous endoscopic gastrostomy (PEG): patients with several co-morbidities are underrepresented in clinical trials, so the best long-term strategy for anticoagulation is difficult to ascertain. The aim of the present report was to evaluate the safety and efficacy of edoxaban administered via PEG in a patient with heart failure and a history of atrial fibrillation affected by amyotrophic lateral sclerosis (ALS). A 71-year-old man with atrial fibrillation, advanced ALS, type II diabetes mellitus, and hypertension presented to the emergency department with dyspnoea and tachycardia. Because vitamin K antagonist and rivaroxaban 15 mg were dropped because of difficult international normalized ratio control (time in therapeutic range <30%) and severe haematuria, respectively, edoxaban 30 mg (crushed pill) daily was administered based on the patient's weight of 58 kg. Mean edoxaban plasma concentration-time profiles were measured, as anti-Xa activity, 2 h before and at 2, 6, and 22 h after drug administration and then compared with the pharmacokinetic profile of edoxaban 30 mg in healthy subjects. An additional testing of steady-state peak plasma concentration of edoxaban after 10 days and a 30 day follow-up were evaluated. The values of the pharmacokinetic parameters, analysed with a non-compartmental analysis by PKSolver module, showed that Cmax and AUC0→t were only slightly higher than those observed in healthy subjects, while the half-life and observed clearance were significantly longer and lower, respectively, than in normal subjects. Steady-state peak plasma concentration of edoxaban was very similar to the levels reported in healthy subjects, and neither relevant bleeding nor thromboembolic event was reported at a 30 day follow-up. These results support safe and effective anticoagulation with edoxaban 30 mg but suggest caution with the use of full dose of edoxaban (60 mg daily) in this kind of patients. We report, for the first time, a safe and effective anticoagulation based on the administration of edoxaban 30 mg daily through PEG in a patient with advanced ALS, acute respiratory, and heart failure, presenting with Takotsubo syndrome and atrial fibrillation.
- [Major gastrointestinal hemorrhage during anticoagulant therapy in patients with atrial fibrillation: when should treatment be resumed?] [Journal Article]
- GIG Ital Cardiol (Rome) 2019; 20(6):367-373
- In patients with atrial fibrillation (AF) under oral anticoagulant therapy (OAT), over half of the hemorrhagic complications occur in the gastrointestinal (GI) tract, with an incidence of 1-4% per ye…
In patients with atrial fibrillation (AF) under oral anticoagulant therapy (OAT), over half of the hemorrhagic complications occur in the gastrointestinal (GI) tract, with an incidence of 1-4% per year. This complication mainly involves older patients, often very compromised from the clinical point of view; mortality rates are not negligible, varying between 4% and 15%. The purpose of the present review was to evaluate the utility of resuming OAT after a major GI hemorrhage in patients with AF. Four observational studies were found in the literature that specifically investigated this issue; three of them had a retrospective design. In these studies almost exclusively warfarin was utilized. OAT was discontinued in all patients at the beginning of GI hemorrhage; in about half of the patients anticoagulation was then restarted and in the other half it was definitively stopped. The results of these studies suggest a beneficial effect of OAT resumption, since it reduced the incidence of thromboembolic events and mortality with a not marked increase in hemorrhagic recurrences. However, these results should be interpreted with caution since, very likely, OAT was resumed in patients in good clinical condition - as suggested by the very low mortality rate during hemorrhagic recurrences (0.7%) - and not in those with very severe hemorrhage and/or very compromised from the clinical point of view. Because of this type of patient selection, we do not know the real hemorrhagic risk in patients resuming OAT after GI hemorrhage. This is a strong limitation in the decision making; in order to acquire this knowledge, randomized studies should be carried out. The evaluation whether or not to restart OAT should be made in the clinical context by a team including the gastroenterologist (or the physician taking care of the GI pathology) and the cardiologist. At present, clinical variables such as site and/or cause of GI bleeding, severity of the anemia and the degree of prolongation of the international normalized ratio, do not appear useful for decision making. The available data suggest that OAT should be resumed in "robust" elderly patients, if the source of bleeding has been identified and corrected, whereas in frail patients and/or with multiple comorbidities, the doubt often remains. The available literature does not offer clear data on the optimal duration of OAT discontinuation after an episode of major GI bleeding. The evaluation should be made in the clinical context; however, therapy discontinuation between 1 week and 1 month appears to be adequate in most cases. On the basis of indirect comparisons, which show many limitations, the most appropriate anticoagulants after GI hemorrhage appear to be warfarin, apixaban and low-dose edoxaban.
- The impact of prothrombin complex concentrates when treating DOAC-associated bleeding: a review. [Review]
- IJInt J Emerg Med 2018 Dec 03; 11(1):55
- CONCLUSIONS: Ultimately, a multimodal approach may be the optimal strategy to restore haemostasis in patients presenting with DOAC-associated coagulopathy.
- [Dissolution and maintenance of portal vein thrombosis with antithrombin III and edoxaban in liver cirrhosis:a case report]. [Journal Article]
- NSNihon Shokakibyo Gakkai Zasshi 2019; 116(6):523-530
- A male patient in his 70s was referred to our department. He was found to have alcoholic liver cirrhosis, esophageal varices, and portal vein thrombosis. Antithrombin III (ATIII) formulation was admi…
A male patient in his 70s was referred to our department. He was found to have alcoholic liver cirrhosis, esophageal varices, and portal vein thrombosis. Antithrombin III (ATIII) formulation was administered. The thrombus was almost completely lysed 2 days after administration. Because portal vein thrombosis could recur, edoxaban, a direct oral anticoagulant (DOAC), was introduced to prevent recurrence. After 4 months, he showed no recurrence of portal vein thrombosis. In the present case, the combination of an ATIII formulation as initial treatment and edoxaban as maintenance therapy was safe and effective. The combination of ATIII and edoxaban may be a treatment option for patients with portal vein thrombosis.
- Reversal of oral anticoagulation in patients with acute intracerebral hemorrhage. [Review]
- CCCrit Care 2019 Jun 06; 23(1):206
- In light of an aging population with increased cardiovascular comorbidity, the use of oral anticoagulation (OAC) is steadily expanding. A variety of pharmacological alternatives to vitamin K antagoni…
In light of an aging population with increased cardiovascular comorbidity, the use of oral anticoagulation (OAC) is steadily expanding. A variety of pharmacological alternatives to vitamin K antagonists (VKA) have emerged over recent years (direct oral anticoagulants, DOAC, i.e., dabigatran, rivaroxaban, apixaban, and edoxaban) which show a reduced risk for the occurrence of intracerebral hemorrhage (ICH). Yet, in the event of ICH under OAC (OAC-ICH), hematoma characteristics are similarly severe and clinical outcomes likewise substantially limited in both patients with VKA- and DOAC-ICH, which is why optimal acute hemostatic treatment in all OAC-ICH needs to be guaranteed. Currently, International Guidelines for the hemostatic management of patients with OAC-ICH are updated as several relevant large-sized observational studies and recent trials have established treatment approaches for both VKA- and DOAC-ICH. While the management of VKA-ICH is mainly based on the immediate reversal of elevated levels of international normalized ratio using prothrombin complex concentrates, hemostatic management of DOAC-associated ICH is challenging requiring specific antidotes, notably idarucizumab and andexanet alfa. This review will provide an overview of the latest studies and trials on hemostatic reversal agents and timing and summarizes the effects on hemorrhage progression and clinical outcomes in patients with OAC-ICH.
- Deep vein thrombosis: update on diagnosis and management. [Review]
- MJMed J Aust 2019 Jun 02
- Diagnosis of deep vein thrombosis (DVT) requires a multifaceted approach that includes clinical assessment, evaluation of pre-test probability, and objective diagnostic testing. Common symptoms and s…
Diagnosis of deep vein thrombosis (DVT) requires a multifaceted approach that includes clinical assessment, evaluation of pre-test probability, and objective diagnostic testing. Common symptoms and signs of DVT are pain, swelling, erythema and dilated veins in the affected limb. The pre-test probability of DVT can be assessed using a clinical decision rule that stratifies DVT into "unlikely" or "likely". If DVT is "unlikely", refer for D-dimer test. If the D-dimer level is normal, DVT can be excluded; if the D-dimer level is increased, refer for compression ultrasound. If DVT is "likely", refer for compression ultrasound. When DVT is confirmed, anticoagulation is indicated to control symptoms, prevent progression and reduce the risk of post-thrombotic syndrome and pulmonary embolism. Anticoagulation may consist of a parenteral anticoagulant overlapped by warfarin or followed by a direct oral anticoagulant (DOAC) (dabigatran or edoxaban), or of a DOAC (apixaban or rivaroxaban) without initial parenteral therapy. DOACs are the preferred treatment for DVT because they are at least as effective, safer and more convenient than warfarin. DOACs may require dose reduction or avoidance in patients with renal dysfunction, and should be avoided in pregnancy. Recent evidence shows that DVT in patients with cancer may be treated with edoxaban (after discontinuation of 5 days of initial heparin or low molecular weight heparin [LMWH]) or rivaroxaban if patients prefer not to have daily injections of LMWH, but the risk of gastrointestinal bleeding is higher with DOACs than with LMWH in patients with gastrointestinal cancer.
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- Evaluation of Direct Oral Anticoagulant Dosing and Monitoring in Two Geriatric Outpatient Clinics. [Journal Article]
- SCSr Care Pharm 2019 Mar 01; 34(3):192-205
- CONCLUSIONS: Results suggest that DOACs used in outpatient geriatric patients are frequently dosed inconsistent with FDA-approved dosing recommendations. Further research is needed regarding clinical outcomes in older patients receiving DOACs and in those with dose adjustments inconsistent with FDA-labeled recommendations.<br/>.