Research Trends in Anticoagulation Therapy over the Last 25 Years

2020 ◽  
Vol 46 (08) ◽  
pp. 919-931
Author(s):  
Mustafa K. Mian ◽  
Subhashaan Sreedharan ◽  
Neeraj S. Limaye ◽  
Chris Hogan ◽  
Jai N. Darvall
Keyword(s):  
Conflicts Of Interest ◽  
Relative Rate ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Citation Count ◽  
Anticoagulation Therapy ◽  
Journal Title ◽  
Common Source ◽  
Level I ◽  
High Level

AbstractA large volume of literature has become available to practitioners prescribing anticoagulants. The aim of this study was to analyze the bibliometric characteristics of the top 100 most cited articles related to anticoagulation over the past 25 years, with special consideration to impact of direct or “nonvitamin K antagonist” oral anticoagulants (NOACs) compared with vitamin K antagonists. A bibliometric analysis of the 100 most cited journal articles related to anticoagulants published between 1994 and 2019 was performed in April 2019. The top 100 articles by citation count were analyzed to extract bibliometric data related to journal title, impact factor, year of publication, place of publication, anticoagulant studied, indication for anticoagulation, study design, and conflicts of interest. The median (interquartile range) number of citations per article was 806 (621–1,085). The anticoagulant most frequently researched was warfarin (37%). NOAC publications (21%) grew at a relative rate of 3.4 times faster compared with all publications. The indication most commonly researched was venous thromboembolism (26%). Eighty articles constituted level I or II evidence, with randomized controlled trials the most common type of study (74). A financial conflict of interest was declared in 87% of articles with private, for-profit organizations the most common source of funding (26%). In summary, top research related to anticoagulation is highly impactful but may be at risk of sponsorship bias. High-level evidence for NOACs continues to expand across a range of indications with citation metrics likely to soon approach or surpass that of older drugs.

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.

scholarly journals New Oral Anticoagulants: An Update

2019 ◽  
Vol 37 (3) ◽  
pp. 135-150
Author(s):  
Quamruddin Ahmad ◽  
Md Mahin Reza ◽  
Md Ahosan Habib ◽  
Syed Faravee Masud ◽  
Nasiruddin ◽  
...  
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Mechanical Heart Valve ◽  
The United States ◽  
Medical Intervention ◽  
New Drugs ◽  
Thrombin Inhibitor ◽  
Valve Prosthesis ◽  
Coronary Syndrome

One of the most common and useful forms of medical intervention is anticoagulant therapy and it is the mainstay of treatment and prevention of thrombosis in different clinical settings, like atrial fibrillation (AF), acute coronary syndrome (ACS), acute venous thromboembolism (VTE), and in patients undergoing invasive cardiac procedures. More than 6 million patients in the United States receive long-term anticoagulation therapy for the prevention of thromboembolism due to AF, placement of a mechanical heart-valve prosthesis, or VTE.1 For more than 60 years, until 2009, warfarin and other vitamin K antagonists were the only class of oral anticoagulants (OAC) available. Although these drugs are highly effective in prevention of TE, their use is limited by a narrow therapeutic index that necessitates frequent monitoring and dose adjustments. This results in substantial risk and inconvenience, leading to inadequate anticoagulant prophylaxis. Recently some new OAC have been marketed which are effective, easier to use and has less side effects. Dabigatran is a new oral thrombin inhibitor and Rivaroxaban, Apixaban and Edoxaban are oral factor Xa inhibitors. This review outlines why these new OACs were essential and describes in detail about these new drugs. J Bangladesh Coll Phys Surg 2019; 37(3): 135-150

Left ventricular thrombosis: new perspectives on an old problem

2020 ◽  
Author(s):  
Mauro Massussi ◽  
Andrea Scotti ◽  
Gregory Y H Lip ◽  
Riccardo Proietti
Keyword(s):  
Clinical Practice ◽  
Tissue Injury ◽  
Thrombus Formation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Blood Stasis ◽  
Chronic Phase ◽  
Left Ventricular ◽  
Bleeding Complications

Abstract Left ventricular thrombosis (LVT) is a major risk factor for systemic thromboembolism and might complicate both the acute and the chronic phase of ischaemic heart disease after myocardial infarction and, less frequently, non-ischaemic cardiomyopathies. The pathophysiology of thrombus formation is complex and involves the three aspects of Virchow’s triad: blood stasis, prothrombotic state, and tissue injury. Advances in technology have improved the detection rate of intracardiac thrombi, but several uncertainties still remain regarding the optimal treatment strategy within daily clinical practice. Of note, anticoagulation therapy with heparin and vitamin K antagonists decreases the risk of embolic stroke though exposing patients to an undeniable risk of bleeding complications. Although limited data on the off-label use of direct oral anticoagulants have reported safety and efficacy for LVT resolution, yet more evidence is needed to justify their use in clinical practice.

scholarly journals Proximal femur fractures in patients taking anticoagulants

2020 ◽  
Vol 5 (10) ◽  
pp. 699-706
Author(s):  
Ioannis V. Papachristos ◽  
Peter V. Giannoudis
Keyword(s):  
Hip Fracture ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Femoral Fractures ◽  
Hip Fracture Surgery ◽  
Femur Fractures ◽  
Intravenous Vitamin ◽  
High Level

Thirty per cent of patients presenting with proximal femoral fractures are receiving anticoagulant treatment for various other medical reasons. This pharmacological effect may necessitate reversal prior to surgical intervention to avoid interference with anaesthesia or excessive peri/post-operative bleeding. Consequently, delay to surgery usually occurs. Platelet inhibitors (aspirin, clopidogrel) either alone or combined do not need to be discontinued to allow acute hip surgery. Platelet transfusions can be useful but are rarely needed. Vitamin K antagonists (VKA, e.g. warfarin) should be reversed in a timely fashion and according to established readily accessible departmental protocols. Intravenous vitamin K on admission facilitates reliable reversal, and platelet complex concentrate (PCC) should be reserved for extreme scenarios. Direct oral anticoagulants (DOAC) must be discontinued prior to hip fracture surgery but the length of time depends on renal function ranging traditionally from two to four days. Recent evidence suggests that early surgery (within 48 hours) can be safe. No bridging therapy is generally recommended. There is an urgent need for development of new commonly available antidotes for every DOAC as well as high-level evidence exploring DOAC effects in the acute hip fracture surgical setting. Cite this article: EFORT Open Rev 2020;5:699-706. DOI: 10.1302/2058-5241.5.190071

The Effectiveness and Safety of Direct Oral Anticoagulants (DOACs) Vs. Traditional Anticoagulants in Patients with Cirrhosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5015-5015
Author(s):  
Justin Hum ◽  
Janice Jou ◽  
Thomas G. Deloughery ◽  
Joseph Shatzel
Keyword(s):  
Major Bleeding ◽  
Conflicts Of Interest ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Complications ◽  
Efficacy And Safety ◽  
Recurrent Thrombosis ◽  
Bleeding Events ◽  
Cirrhotic Patients

Abstract Introduction: The coagulopathy associated with cirrhosis is complex and places patients at risk for both bleeding and thrombosis. Direct oral anticoagulants (DOACs) have been shown to have superior efficacy and safety compared to vitamin K antagonists; however their efficacy and safety in cirrhotic patients is not clear. The aim of this study is to retrospectively compare the effectiveness and bleeding complications of DOACs as compared to traditional anticoagulants in cirrhotic patients. Methods: This study was a retrospective review of patients treated at a single academic center between 2012-2015 who were prescribed a DOAC (apixaban or rivaroxaban), or a traditional anticoagulant (warfarin or low molecular weight heparin), with an ICD-9 code for the diagnosis of cirrhosis. The primary outcomes of interest are recurrent thrombosis or stroke (efficacy failure), or bleeding events (safety failure). Major bleeds were characterized as fatal bleeding, symptomatic bleeding in critical organ area, or bleeding causing a fall in hemoglobin level >2 or leading to transfusion of 2+ units of packed red blood cells. Results: During the study period, 27 cirrhotic patients were prescribed a DOAC and 18 were prescribed a traditional anticoagulant (either LMWH or warfarin). Both groups had similar total bleeding events (8 DOAC vs. 10 traditional anticoagulation, p = 0.12). There were significantly less major bleeding episodes in the DOAC group, (1 (4%) vs. 5 (28%), p = 0.03) and less intracranial bleeding (3 (17% ) vs. 0 (0%) p=0.06). Recurrent thrombosis or stroke occurred in 1 (4%) patient in the DOAC group and 1 (6%) patient in the traditional group (p = 1.0). Conclusions: Anticoagulation with DOACs in cirrhotic patients may be as safe as traditional anticoagulants with respect to bleeding events. Patients with cirrhosis at our center prescribed DOACs had less major bleeding events, while maintaining efficacy at preventing stroke or recurrent thrombosis. Table Table. Disclosures No relevant conflicts of interest to declare.

Safety and Feasibility of Treatment with Rivaroxaban in Children for Non-Routine Indications: A Case Series Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5014-5014 ◽  
Author(s):  
Kathryn E. Dickerson ◽  
Ravi Sarode ◽  
Ayesha Zia
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Case Series ◽  
Bleeding Complications ◽  
Fixed Dose ◽  
The Mean ◽  
Recurrent Vte

Background. Anticoagulation therapy is the cornerstone of acute treatment of venous thromboembolism (VTE) and for prevention of recurrent VTE. The need for anticoagulation is increasing in children, largely in part due to increasing VTE rates. Conventional anticoagulants, including heparin, low-molecular weight heparins (LMWH), Fondaparinux, and vitamin K antagonists (VKA) are widely used in children but have limitations. Standard of care management with these agents is plagued with the trade-off between daily or twice daily injections or frequent monitoring of therapeutic effect. The advent of direct oral anticoagulants (DOACs) have catalyzed significant changes in the therapeutic landscape of VTE management. DOACs have been evaluated for safety and efficacy in large, randomized controlled trials in the treatment and prevention of VTE in adults, with results that are comparable to conventional therapy. None of the current DOACs have FDA-approved indications and dosing in children yet. Off-label use of these agents is largely based on adult data and doses, and is increasing at many Children's Hospitals across US. Rivaroxaban, a DOAC, is a factor Xa inhibitor with predictable pharmacokinetic and pharmacodynamics properties. Methods. We describe a case series of 8 unique pediatric cases, treated with Rivaroxaban, for a variety of non-routine indications, due either to adverse effects, intolerability of LMWH or VKA or the need for ongoing, long term anticoagulation. Rivaroxaban was started after informed consent and assent from parents or patients respectively, and was initiated at a fixed dose but titrated to a final dose after monitoring of trough and peak Rivaroxaban levels (Aniara, West Chester,OH, USA). Results. The mean age of patients in this case series is 14 years (median: 16, range 3-17) (see Table). The most common indication to use Rivaroxaban was the need for long term anticoagulation after having completed therapeutic anticoagulation, except in two patients, one of whom developed warfarin skin necrosis due to protein C deficiency and another with heparin induced thrombocytopenia. Only two patients needed dose adjustments to achieve target trough and peak drug levels. The mean duration of follow-up is 9 months (median= 5.5; range 3-24) (see Table) at this time. None of the patients developed recurrent VTE while on Rivaroxaban. A soft tissue traumatic bleed occurred in one patient which was treated with holding off the drug for 48 hours. No other bleeding complications were observed. Conclusions. Clinical application of DOACs in a real world clinical setting, including strong thrombophilia and malignancy, results in treatment profile of high efficacy and safety in children; however, larger studies are needed to validate these findings. Disclosures Sarode: CSL Behring: Consultancy, Honoraria.

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 Practical Considerations for the Use of Direct Oral Anticoagulants in Patients With Atrial Fibrillation

2016 ◽  
Vol 23 (1) ◽  
pp. 5-19 ◽  
Author(s):  
Zachary Stacy ◽  
Sara Richter
Keyword(s):  
Atrial Fibrillation ◽  
Treatment Guidelines ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Significant Risk ◽  
The United States ◽  
Assessment Tools ◽  
Long Term Outcome

Atrial fibrillation (AF) is a significant risk factor for stroke and peripheral thromboembolic events (TEs). Preventing blood clots in the heart to reduce stroke and TE risk is a key goal of AF therapy. Traditional stroke risk assessment tools for patients with nonvalvular AF include the CHADS2 and CHA(2)DS(2)-VASc scores, while long-term outcome data with the newer direct oral anticoagulants (DOACs) are emerging. The goals of this review were to assess traditional therapies and existing treatment guidelines and to discuss key pharmacologic properties of the DOACS, noting how these may benefit at-risk patients with AF. This narrative review was developed on the basis of the authors’ clinical knowledge, extensive reading of the literature, and broad pharmacy experience in the management of patients with AF. Limitations of oral vitamin K antagonists (VKAs) include slow onset of action, the need for regular monitoring of their anticoagulation effect, significant food and drug interactions, and unpredictable dose–response properties. Key clinical trial data led to the approvals of apixaban, dabigatran etexilate, edoxaban, and rivaroxaban in the United States to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF. With predictable pharmacologic properties and limited drug and/or dietary interactions, the DOACs offer several benefits over traditional oral anticoagulation therapy with VKA. However, they have limitations, including the absence of immediate reversal agents and limited options for monitoring their anticoagulation effects in clinical practice. As experience with the use of DOACs grows, optimized treatment regimens and improved patient care are expected.

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.

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