New developments in anticoagulants: Past, present and future

2017 ◽  
Vol 117 (07) ◽  
pp. 1283-1288 ◽  
Author(s):  
Jeffrey I. Weitz ◽  
Job Harenberg
Keyword(s):  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Factor Xii ◽  
Heparin Induced Thrombocytopenia ◽  
New Developments ◽  
Oral Anticoagulation Therapy ◽  
Reversal Agents ◽  
The Past

SummaryThrombosis is a leading cause of death and disability worldwide, and anticoagulants are the mainstay of its prevention and treatment. Starting with unfractionated heparin (UFH) and vitamin K antagonists (VKAs) such as warfarin, the choices of anticoagulants have exploded in the past 20 years. With over 90% subcutaneous bioavailability, no need for coagulation monitoring and dose adjustment, and a lower risk of heparin-induced thrombocytopenia, low-molecular-weight heparin and fondaparinux have replaced UFH for prevention and initial treatment of venous thromboembolism and for secondary prevention in cancer patients. In patients undergoing percutaneous interventions, bivalirudin is often used instead of UFH. Oral anticoagulation therapy has advanced with the introduction of the non-vitamin K antagonist oral anticoagulants (NOACs), which include dabigatran, rivaroxaban, apixaban and edoxaban. With efficacy at least equal to that of VKAs but with greater safety and convenience, the NOACs are now replacing VKAs for many indications. This paper a) highlights these advances, b) outlines how specific reversal agents for the NOACs will enhance their safety, c) reviews some of the ongoing trials with the NOACs, and d) describes the inhibitors of factor XII and XI that are under investigation as anticoagulants.

scholarly journals Chronic Oral Anticoagulation and Clinical Outcome in Hospitalized COVID-19 Patients

2021 ◽  
Author(s):  
Vincenzo Russo ◽  
Roberta Bottino ◽  
Antonello D’Andrea ◽  
Angelo Silverio ◽  
Marco Di Maio ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Vitamin K ◽  
Oral Anticoagulation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Study Groups ◽  
Oral Anticoagulation Therapy ◽  
Risk Of Mortality ◽  
Artery Disease

Abstract Purpose The clinical course of COVID-19 may be complicated by acute respiratory distress syndrome (ARDS) and thromboembolic events, which are associated with high risk of mortality. Although previous studies reported a lower rate of death in patients treated with heparin, the potential benefit of chronic oral anticoagulation therapy (OAT) remains unknown. We aimed to investigate the association between OAT with the risk of ARDS and mortality in hospitalized patients with COVID-19. Methods This is a multicenter retrospective Italian study including consecutive patients hospitalized for COVID-19 from March 1 to April 22, 2020, at six Italian hospitals. Patients were divided into two groups according to the chronic assumption of oral anticoagulants. Results Overall, 427 patients were included; 87 patients (19%) were in the OAT group. Of them, 54 patients (13%) were on treatment with non-vitamin k oral anticoagulants (NOACs) and 33 (8%) with vitamin-K antagonists (VKAs). OAT patients were older and had a higher rate of hypertension, diabetes, and coronary artery disease compared to No-OAT group. The rate of ARDS at admission (26% vs 28%, P=0.834), or developed during the hospitalization (9% vs 10%, P=0.915), was similar between study groups; in-hospital mortality (22% vs 26%, P=0.395) was also comparable. After balancing for potential confounders by using the propensity score matching technique, no differences were found in term of clinical outcome between OAT and No-OAT patients Conclusion Oral anticoagulation therapy, either NOACs or VKAs, did not influence the risk of ARDS or death in patients hospitalized with COVID-19.

Perioperative Management of Patients Receiving New Anticoagulants

2019 ◽  
Vol 25 (19) ◽  
pp. 2149-2157 ◽  
Author(s):  
Massimo Lamperti ◽  
Andrey Khozenko ◽  
Arun Kumar
Keyword(s):  
Vitamin K ◽  
Elective Surgery ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Oral Intake ◽  
Bleeding Risk ◽  
Dietary Vitamin ◽  
Reversal Agent ◽  
Onset Of Action ◽  
Reversal Agents

There is an increased use of oral anticoagulants for the prevention of venous and arterial thrombosis. Vitamin-K antagonists have been used for decades as the main oral anticoagulants but they have the draback a complex therapeutic management, slow onset of action and by a different oral intake caused by dietary vitamin K intake. New non-vitamin K antagonist oral anticoagulants (NOACs) have been developed to overcome the limitations of warfarin. Their management is easier as it requires a fixed daily dose without coagulation monitoring. Although their therapeutic profile is safe, proper attention should be paid in case of unexpected need for the reversal of their coagulation effect and in case a patient needs to have a scheduled surgery. For non-acute cardiac surgery, discontinuation of NOACs should start at least 48 hours prior surgery. Intracranial bleedings associated with NOACs are less dangerous comparing to those warfarin-induced. NOACs need to be stopped ≥24 hours in case of elective surgery for low bleeding-risk procedures and ≥48 hours for high bleeding-risk surgery in patients with normal renal function and 72 hours in case of reduced CrCl < 80. The therapy with NOACs should be resumed from 48 to 72 hours after the procedure depending on the perceived bleeding, type of surgery and thrombotic risks. There are some available NOAC reversal agents acting within 5 to 20 minutes. In case of lack of reversal agent, adequate diuresis, renal replacement therapy and activated charcoal in case of recent ingestion should be considered.

scholarly journals Anticoagulation in Atrial Fibrillation Cardioversion: What Is Crucial to Take into Account

2021 ◽  
Vol 10 (15) ◽  
pp. 3212
Author(s):  
Fabiana Lucà ◽  
Simona Giubilato ◽  
Stefania Angela Di Fusco ◽  
Laura Piccioni ◽  
Carmelo Massimiliano Rao ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Thrombus Formation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Significant Advance ◽  
Thromboembolic Events ◽  
Thromboembolic Risk ◽  
Pharmacological Cardioversion

The therapeutic dilemma between rhythm and rate control in the management of atrial fibrillation (AF) is still unresolved and electrical or pharmacological cardioversion (CV) frequently represents a useful strategy. The most recent guidelines recommend anticoagulation according to individual thromboembolic risk. Vitamin K antagonists (VKAs) have been routinely used to prevent thromboembolic events. Non-vitamin K antagonist oral anticoagulants (NOACs) represent a significant advance due to their more predictable therapeutic effect and more favorable hemorrhagic risk profile. In hemodynamically unstable patients, an emergency electrical cardioversion (ECV) must be performed. In this situation, intravenous heparin or low molecular weight heparin (LMWH) should be administered before CV. In patients with AF occurring within less than 48 h, synchronized direct ECV should be the elective procedure, as it restores sinus rhythm quicker and more successfully than pharmacological cardioversion (PCV) and is associated with shorter length of hospitalization. Patients with acute onset AF were traditionally considered at lower risk of thromboembolic events due to the shorter time for atrial thrombus formation. In patients with hemodynamic stability and AF for more than 48 h, an ECV should be planned after at least 3 weeks of anticoagulation therapy. Alternatively, transesophageal echocardiography (TEE) to rule out left atrial appendage thrombus (LAAT) should be performed, followed by ECV and anticoagulation for at least 4 weeks. Theoretically, the standardized use of TEE before CV allows a better stratification of thromboembolic risk, although data available to date are not univocal.

HEMATURIA AND OTHER KINDS OF BLEEDINGS ON NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION: AN UPDATED OVERVIEW ON OCCURRENCE, PATHOMECHANISMS AND MANAGEMENT

2020 ◽  
Vol 73 (11) ◽  
pp. 2528-2534
Author(s):  
Dagmara Wojtowicz ◽  
Anna Tomaszuk-Kazberuk ◽  
Jolanta Małyszko ◽  
Marek Koziński
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Anticoagulant Activity ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Bleeding Complications ◽  
Reversal Agents ◽  
Limited Availability ◽  
Increased Risk

Non-vitamin K antagonist oral anticoagulants (NOACs) are currently recommended for oral anticoagulation in patients with non-valvular atrial fibrillation. In the setting, NOACs effectively prevent from stroke and systemic embolic events. In spite of the favorable safety profile of NOACs when compared with vitamin K antagonists, the use of any kind of anticoagulation is associated with an increased risk of bleeding. However, there is still a lack of direct comparisons of effectiveness and safety among NOACs. The results of indirect comparisons and meta-analyses suggest that the risk of various types of hemorrhagic complications differ among the particular NOACs. Management of bleeding in patients under NOAC therapy can be challenging because of limited availability of antidotes and the lack of routine laboratory test monitoring the NOAC anticoagulant effect. In case of life-threatening or critical site bleeding, reversal of NOAC anticoagulant activity is essential together with immediate implementation of causative treatment. Moreover, some patients on chronic NOAC therapy may require urgent surgery or invasive procedures. Specific reversal agents for NOACs have been developed, i.e. more widely available idarucizumab for the factor IIa inhibitor (dabigatran) and andexanet alfa for the factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) with limited availability. This review summarizes the occurrence and management of NOAC-related bleeding complications with a particular emphasis on hematuria.

POST-NOAC: Portuguese observational study of intracranial hemorrhage on non-vitamin K antagonist oral anticoagulants

2016 ◽  
Vol 12 (6) ◽  
pp. 623-627 ◽  
Author(s):  
Cláudia Marques-Matos ◽  
José Nuno Alves ◽  
João Pedro Marto ◽  
Joana Afonso Ribeiro ◽  
Ana Monteiro ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Functional Outcome ◽  
Intracranial Hemorrhage ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Vitamin K Antagonist ◽  
Significant Shift ◽  
Modified Rankin Scale

Background There is a lower reported incidence of intracranial hemorrhage with non-vitamin K antagonist oral anticoagulants compared with vitamin K antagonist. However, the functional outcome and mortality of intracranial hemorrhage patients were not assessed. Aims To compare the outcome of vitamin K antagonists- and non-vitamin K antagonist oral anticoagulants-related intracranial hemorrhage. Methods We included consecutive patients with acute non-traumatic intracranial hemorrhage on oral anticoagulation therapy admitted between January 2013 and June 2015 at four university hospitals. Clinical and demographic data were obtained from individual medical records. Intracranial hemorrhage was classified as intracerebral, extra-axial, or multifocal using brain computed tomography. Three-month functional outcome was assessed using the modified Rankin Scale. Results Among 246 patients included, 24 (9.8%) were anticoagulated with a non-vitamin K antagonist oral anticoagulants and 222 (90.2%) with a vitamin K antagonists. Non-vitamin K antagonist oral anticoagulants patients were older (81.5 vs. 76 years, p = 0.048) and had intracerebral hemorrhage more often (83.3% vs. 63.1%, p = 0.048). We detected a non-significant trend for larger intracerebral hemorrhage volumes in vitamin K antagonists patients ( p = 0.368). Survival analysis adjusted for age, CHA2DS2VASc, HAS-BLED, and anticoagulation reversal revealed that non-vitamin K antagonist oral anticoagulants did not influence three-month mortality (hazard ratio (HR) = 0.83, 95% confidence interval (CI) = 0.39–1.80, p = 0.638). Multivariable ordinal regression for three-month functional outcome did not show a significant shift of modified Rankin Scale scores in non-vitamin K antagonist oral anticoagulants patients (odds ratio (OR) 1.26, 95%CI 0.55–2.87, p = 0.585). Conclusions We detected no significant differences in the three-month outcome between non-vitamin K antagonist oral anticoagulants- and vitamin K antagonists-associated intracranial hemorrhage, despite unavailability of non-vitamin K antagonist oral anticoagulants-specific reversal agents.

scholarly journals 2021 Korean Heart Rhythm Society Guidelines for Stroke Prevention in Atrial Fibrillation

2021 ◽  
Vol 96 (4) ◽  
pp. 296-311
Author(s):  
Ki Hong Lee ◽  
Jin-Bae Kim ◽  
Seung Yong Shin ◽  
Boyoung Joung
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Stroke Prevention ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Optimal Strategies ◽  
Mechanical Valve ◽  
Heart Rhythm ◽  
Bleeding Risk

Atrial fibrillation (AF) is a strong risk factor for ischemic stroke and systemic embolism. To prevent thromboembolic events in patients with AF, anticoagulation therapy is essential. The anticoagulant strategy is determined after stroke and bleeding risk assessments using the CHA2DS2-VASc and HAS-BLED scores, respectively; both consider clinical risk factors. Vitamin K antagonists (VKAs) are the sole anticoagulant option in AF patients with a prosthetic mechanical valve or moderate-severe mitral stenosis; in all other AF patients VKA or non-vitamin K antagonist oral anticoagulants are therapeutic options. However, antiplatelet therapy should not be used for stroke prevention in AF patients. Anticoagulation is not needed in AF patients with low stroke risk but strongly recommended in those with a with low bleeding risk. Left atrial appendage (LAA) occlusion offers an alternative in AF patients in whom long-term anticoagulation is contraindicated. Surgical occlusion or the exclusion of LAA can be considered for stroke prevention in AF patients undergoing cardiac surgery. In this article, we review existing data for stroke prevention and suggest optimal strategies to prevent stroke in AF patients.

Anticoagulation in Deep Venous Thrombosis: Current Trends in the Era of Non- Vitamin K Antagonists Oral Anticoagulants

2020 ◽  
Vol 26 (23) ◽  
pp. 2692-2702 ◽  
Author(s):  
Panteleimon E. Papakonstantinou ◽  
Costas Tsioufis ◽  
Dimitris Konstantinidis ◽  
Panagiotis Iliakis ◽  
Ioannis Leontsinis ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Vitamin K ◽  
Safety Profile ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Bleeding Risk ◽  
Efficacy And Safety ◽  
Anticoagulation Management ◽  
Oral Agents

: Anticoagulation therapy is the cornerstone of treatment in acute vein thrombosis (DVT) and it aims to reduce symptoms, thrombus extension, DVT recurrences, and mortality. The treatment for DVT depends on its anatomical extent, among other factors. Anticoagulation therapy for proximal DVT is clearly recommended (at least for 3 months), while AT for isolated distal DVT should be considered, especially in the presence of high thromboembolic risk factors. The optimal anticoagulant and duration of therapy are determined by the clinical assessment, taking into account the thromboembolic and bleeding risk in each patient in a case-by-case decision making. Non-Vitamin K antagonists oral anticoagulants (NOACs) were a revolution in the anticoagulation management of DVT. Nowadays, NOACs are considered as first-line therapy in the anticoagulation therapy for DVT and are recommended as the preferred anticoagulant agents by most scientific societies. NOACs offer a simple route of administration (oral agents), a rapid onset-offset of their action along with a good efficacy and safety profile in comparison with Vitamin K Antagonists (VKAs). However, there are issues about their efficacy and safety profile in specific populations with high thromboembolic and bleeding risks, such as renal failure patients, active-cancer patients, and pregnant women, in which VKAs and heparins were the standard care of treatment. Since the available data are promising for the use of NOACs in end-stage chronic kidney disease and cancer patients, several ongoing randomized trials are currently trying to solve that issues and give evidence about the safety and efficacy of NOACs in these populations.

scholarly journals The prevalence of long-term oral anticoagulation therapy in a cardiology center in Bucharest, Romania

2018 ◽  
Vol 91 (1) ◽  
pp. 37-41
Author(s):  
Adelina-Mihaela Sorescu ◽  
Tudor Enache ◽  
Suzana Guberna
Keyword(s):  
Oral Anticoagulation ◽  
Economic Status ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Cross Sectional Study ◽  
Similar Data ◽  
Cross Sectional ◽  
Oral Anticoagulation Therapy ◽  
Vein Thrombosis

Background and aims. Few studies discuss the prevalence of oral anticoagulation therapy (OAT) in clinical practice, despite their increasing use worldwide. In America, studies established that 20% to 80% of the patients with indication benefit from OAT. In Romania, there is no data regarding the utilization of oral anticoagulants. Thus, this study aims to determine the trends of OAT.Methods. We designed a cross-sectional study of the patients admitted to the Cardiology Department of the “Bagdasar-Arseni” Clinical Emergency Hospital, Bucharest, from the 1st of November 2016 until the 31st of January 2017. We considered OAT indications to be: atrial fibrillation/flutter (AF), pulmonary embolisms (PE), deep vein thrombosis (DVT), intramural or intracavitary thrombi and left ventricle aneurysms. Statistical analysis was performed with EpiInfo.Results. There were 783 patients admitted, 253 of these having an OAT indication (mean age 73.25 years, 53.75% female). Only 162 patients (64.03%) received it, either Vitamin K Antagonists (VKA) (78 patients, 48.14%), or Novel Oral Anticoagulants (NOAC) (84 patients, 51.85%). Reasons for not indicating such therapy included the hemorrhage risk (43.27%), the lack of adherence to the treatment (18.56%), the impossibility of INR monitoring (21.84%), the economic status (10.21%) and others (6.12%). 221 patients had AF (87.35%), 141 (63.8%) receiving OAT, VKA (67 patients, 47.51%), or NOAC (74 patients, 52.48%). 17 patients (6.71%) had a PE and/or DVT. 15 (88.23%) received OAT, AVK (11 patients, 73.33%), or NOAC (4 patients, 26.67%). 15 patients (5.92%) had other OAT indications (excepting AF or PE/DVT), 11 receiving OAT (73.33%), AVK (8 patients, 72.72%), or NOAC (3 patients, 27.27%).Conclusions. Our study determined that 64.03% of those with indication received OAT. Similar data is reported in the USA, suggesting an underuse of anticoagulants. The risk of hemorrhage, lack of adherence, the impossibility of INR monitoring or the economic status were some of the reasons for not recommending OAT.

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