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 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.

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.

Voorkamerfibrillatie en niet-vitamine K-antagonist orale anticoagulantia: van klinische studies tot gebruik in de dagelijkse praktijk

2021 ◽  
Author(s):  
A. CAPIAU ◽  
M. GRYMONPREZ ◽  
T. DE BACKER ◽  
S. GEVAERT ◽  
K. BOUSSERY ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Real Life ◽  
Vitamin K Antagonist ◽  
Fixed Dose ◽  
Stroke Risk Factor

Atrial fibrillation and non-vitamin K antagonist oral anticoagulants: from clinical trials to real-world clinical practice. For decades, vitamin K antagonists (VKAs) were the only oral anticoagulants available for the prevention of thromboembolism in patients with atrial fibrillation (AF). Since 2012, non-vitamin K antagonist oral anticoagulants (NOACs) are available for this indication, which have proven to be at least as effective and safe as VKAs in randomized controlled trials (RCTs). NOACs have additional benefits, such as a fast onset of action, a fixed-dose regimen without requiring regular monitoring, less interactions and less intracranial bleeding. Their emergence has caused a paradigm shift in anticoagulation therapy, with NOACs being the anticoagulant of choice compared to VKAs. Since strict in- and exclusion criteria were used in the pivotal RCTs, concerns have risen regarding the generalizability of these results to real-life clinical practice in patients with multiple comorbidities. In this manuscript, this extrapolation is discussed, focusing on 4 different topics regarding appropriate NOAC use: the management of AF patients with a single stroke risk factor, the importance of an optimal therapy adherence, potential drug-drug interactions with NOACs and addressing a geriatric AF patient after a fall. Hopefully, this manuscript will help guide clinicians in the optimal use of NOACs in their daily clinical practice.

scholarly journals Direct oral anticoagulants: A new chapter in anticoagulation therapy

2020 ◽  
Vol 70 (5) ◽  
pp. 249-268
Author(s):  
Radica Stepanović-Petrović ◽  
Katarina Nastić
Keyword(s):  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Cardiac Biomarkers ◽  
Bleeding Complications ◽  
Comparable Efficacy ◽  
Thrombin Inhibitor ◽  
Severe Bleeding ◽  
Coronary Syndrome

Thromboembolic events are the leading cause of morbidity and mortality worldwide. From the second half of the 20th century, vitamin K antagonists (VKAs), warfarin and acenocoumarol, were the only anticoagulants taken orally. The major reform in anticoagulation therapy was made by the advent of direct oral anticoagulants (DOACs), about 10 years ago. Direct thrombin inhibitor (dabigatran) and direct inhibitors of factor Xa (rivaroxaban, apixaban, edoxaban, and betrixaban) have demonstrated favorable risk/benefit ratio. Compared to warfarin, DOACs are associated with a predictable pharmacokinetic profile, lower severe bleeding complications, particularly intracranial hemorrhages, and minimal drug interactions. Moreover, DOACs achieve a rapid onset of action and have shown comparable efficacy with warfarin and low molecular weight heparin (LMWH) in clinical trials. As a result, DOACs are now replacing VKAs and LMWH for many indications including stroke and systemic embolism prevention in nonvalvular atrial fibrillation, prevention, and treatment of venous thromboembolism and thromboprophylaxis following total knee/hip replacement surgery. In addition, rivaroxaban (in combination with aspirin alone or aspirin and clopidogrel) is used in the prevention of atherothrombotic events following acute coronary syndrome with elevated cardiac biomarkers. In case of severe bleeding complications under DOACs treatment, antidotes are available; idarucizumab for dabigatran reversal and andexanet alfa for rivaroxaban and apixaban.

scholarly journals Impaired kidney function at ED admission: a comparison of bleeding complications of patients with different oral anticoagulants

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Martin Müller ◽  
Michaela Traschitzger ◽  
Michael Nagler ◽  
Spyridon Arampatzis ◽  
Aristomenis K. Exadaktylos ◽  
...  
Keyword(s):  
Renal Function ◽  
Kidney Function ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulation Therapy ◽  
Patient Treatment ◽  
Bleeding Complications ◽  
Study Patient ◽  
Bleeding Events

Abstract Background Up to a fourth of patients at emergency department (ED) presentation suffer from acute deterioration of renal function, which is an important risk factor for bleeding events in patients on oral anticoagulation therapy. We hypothesized that outcomes of patients, bleeding characteristics, therapy, and outcome differ between direct oral anticoagulants (DOACs) and vitamin-K antagonists (VKAs). Methods All anticoagulated patients older than 17 years with an impaired kidney function treated for an acute haemorrhage in a large Swiss university ED from 01.06.2012 to 01.07.2017 were included in this retrospective cohort study. Patient, treatment, and bleeding characteristics as well as outcomes (length of stay ED, intensive care unit and in-hospital admission, ED resource consumption, in-hospital mortality) were compared between patients on DOAC or VKA anticoagulant. Results In total, 158 patients on DOAC and 419 patients on VKA with acute bleeding and impaired renal function were included. The renal function in patients on VKA was significantly worse compared to patients on DOAC (VKA: median 141 μmol/L vs. DOAC 132 μmol/L, p = 0.002). Patients on DOAC presented with a smaller number of intracranial bleeding compared to VKA (14.6% DOAC vs. 22.4% VKA, p = 0.036). DOAC patients needed more emergency endoscopies (15.8% DOAC vs, 9.1% VKA, p = 0.020) but less interventional emergency therapies to stop the bleeding (13.9% DOAC vs. 22.2% VKA, p = 0.027). Investigated outcomes did not differ significantly between the two groups. Conclusions DOAC patients were found to have a smaller proportional incidence of intracranial bleedings, needed more emergency endoscopies but less often interventional therapy compared to patients on VKA. Adapted treatment algorithms are a potential target to improve care in patients with DOAC.

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 Apixaban versus Warfarin in Patients with Left Ventricular (LV) Thrombus, a prospective randomized trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Alcalai ◽  
R Rashad ◽  
A Butnaru ◽  
G Moravsky ◽  
D Leibowitz
Keyword(s):  
Major Bleeding ◽  
Thrombus Formation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Left Ventricular ◽  
Systemic Embolism ◽  
Bleeding Events ◽  
Open Label ◽  
Warfarin Group ◽  
Acute Mi

Abstract Background Patients with acute myocardial infarction (MI) have an elevated risk of stroke, mostly due to left ventricular (LV) thrombus formation, which typically occur within the first 2 weeks following an anterior MI. Currently the recommended management of LV thrombus after acute MI is anticoagulation with vitamin K antagonist. To date, there are no prospective data on the use of direct oral anticoagulants (DOACS) for stroke prevention in the setting of LV thrombus. Aim To assess the efficacy of apixaban vs. warfarin in treating LV thrombus after MI. Methods The study is a prospective, randomized, multi-center open label trial comparing apixaban (at a dose of 5 mg twice daily) with s.c enoxaparin 1mg/kg BID followed by dose-adjusted warfarin to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for 3 months in patients with LV thrombus detected by echocardiography 3 to 14 days after acute MI. The primary outcome was the presence and size of LV thrombus 3 months after initiation of anticoagulation as assessed by 2D echocardiogram. Secondary outcomes were stroke or systemic embolism, major bleeding and death from any cause. Results 25 patients have been enrolled to date in 3 medical centers, 13 were randomized to apixaban and 12 to warfarin. Mean age was 59.8±10.7 and 19 (76%) were males with no difference between the study groups. Mean LV thrombus size at enrollment was 24X15 mm in the apixaban group and 19X14 in the warfarin group (p=NS). After 3 months of treatment thrombus completely resolved in all patients in the warfarin group and in 12 of 13 in the apixaban group. In one patient in the apixaban group who had a very large thrombus of 40x20mm size upon enrollment the thrombus size was reduced significantly to 20x12 after 3 months. No death, stroke or systemic embolism was documented in either group. There were two patients with major bleeding in the warfarin group, one had sub-arachnoid hemorrhage after 2 months and anticoagulation was stopped, and another had GI bleeding after 1 month and was switched to enoxaparin. One patient in the warfarin group refused to continue the treatment after 3 weeks. No major bleeding events were recorded in the apixaban group and all patients completed 3 months of treatment. Conclusions Our preliminary results indicate that apixaban is a safe and effective treatment for patients with LV thrombus post anterior wall MI. Funding Acknowledgement Type of funding source: None

Consideration of non-valvular atrial fibrillation with left atrial appendage thrombus formation despite under appropriate oral anticoagulation therapy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Shiraki ◽  
H Tanaka ◽  
K Yamashita ◽  
Y Tanaka ◽  
K Sumimoto ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Oral Anticoagulation ◽  
Left Atrial ◽  
Thrombus Formation ◽  
Anticoagulation Therapy ◽  
Left Ventricular ◽  
Volume Index ◽  
Oral Anticoagulation Therapy

Abstract Background Atrial fibrillation (AF) is the most frequently sustained cardiac arrhythmia, with a prevalence of about 2–3% in the general population. In accordance with CHADS2 or CHA2DS2-VASc score, appropriate oral anticoagulation therapy such as warfarin or direct oral anticoagulants (DOAC) significantly reduced the risk of thromboembolic events. However, left atrial (LA) thrombus can be detected in the LA appendage (LAA) in AF patients despite appropriate oral anticoagulation therapy. Purpose Our purpose was to investigate the associated factors of LAA thrombus formation in non-valvular atrial fibrillation (NVAF) patients despite under appropriate oral anticoagulation therapy. Methods We retrospectively studied consecutive 286 NVAF patients for scheduled catheter ablation or electrical cardioversion for AF in our institution between February 2017 and September 2019. Mean age was 67.1±9.4 years, 79 patients (29.5%) were female, and 140 (52.2%) were paroxysmal AF. All patients underwent transthoracic and transesophageal echocardiography before catheter ablation or electrical cardioversion. All patients received appropriate oral anticoagulation therapy including warfarin or DOAC for at least 3 weeks prior to transesophageal echocardiography based on the current guidelines. LAA thrombus was defined as an echodense intracavitary mass distinct from the underlying endocardium and not caused by pectinate muscles by at least three senior echocardiologists. Results Of 286 NVAF patients with under appropriate oral anticoagulation therapy, LAA thrombus was observed in 9 patients (3.3%). Univariate logistic regression analysis showed that age, paroxysmal AF, CHADS2 score ≥3, left ventricular end-diastolic volume index (LVEDVI), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), LA volume index (LAVI), mitral inflow E and mitral e' annular velocities ratio (E/e'), and LAA flow were associated with LAA thrombus formation. It was noteworthy that multivariate logistic regression analysis showed that LAA flow was independent predictor of LAA thrombus (OR: 0.72, 95% CI: 0.59–0.89, p<0.005) as well as LVEF. Furthermore, receiver operating characteristic (ROC) curve analysis identified the optimal cutoff value of LAA flow for predicting LAA thrombus as ≤15cm/s, with a sensitivity of 88%, specificity of 93%, and area under the curve (AUC) of 0.95. Conclusions LAA flow was strongly associated with LAA thrombus formation even in NVAF patients with appropriate oral anticoagulation therapy. According to our findings, further strengthen of oral anticoagulation therapy or percutaneous transcatheter closure of the LAA may be considered in NVAF patients with appropriate oral anticoagulation therapy but low LAA flow, especially <15cm/s. Funding Acknowledgement Type of funding source: None

scholarly journals Falls in ED patients: do elderly patients on direct oral anticoagulants bleed less than those on vitamin K antagonists?

2021 ◽  
Vol 29 (1) ◽  
Author(s):  
Martin Müller ◽  
Ioannis Chanias ◽  
Michael Nagler ◽  
Aristomenis K. Exadaktylos ◽  
Thomas C. Sauter
Keyword(s):  
Elderly Patients ◽  
Vitamin K ◽  
Intracranial Haemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Complications ◽  
Lower Odds ◽  
Anticoagulated Patients ◽  
Proportional Incidence

Abstract Background Falls from standing are common in the elderly and are associated with a significant risk of bleeding. We have compared the proportional incidence of bleeding complications in patients on either direct oral anticoagulants (DOAC) or vitamin K antagonists (VKA). Methods Our retrospective cohort study compared elderly patients (≥65 years) on DOAC or VKA oral anticoagulation who presented at the study site – a Swiss university emergency department (ED) – between 01.06.2012 and 01.07.2017 after a fall. The outcomes were the proportional incidence of any bleeding complication and its components (e.g. intracranial haemorrhage), as well as procedural and clinical parameters (length of hospital stay, admission to intensive care unit, in-hospital-mortality). Uni- and multivariable analyses were used to compare the studied outcomes. Results In total, 1447 anticoagulated patients were included – on either VKA (n = 1021) or DOAC (n = 426). There were relatively more bleeding complications in the VKA group (n = 237, 23.2%) than in the DOAC group (n = 69, 16.2%, p = 0.003). The difference persisted in multivariable analysis with 0.7-fold (95% CI: 0.5–0.9, p = 0.014) lower odds for patients under DOAC than under VKA for presenting with any bleeding complications, and 0.6-fold (95% 0.4–0.9, p = 0.013) lower odds for presenting with intracranial haemorrhage. There were no significant differences in the other studied outcomes. Conclusions Among elderly, anticoagulated patients who had fallen from standing, those under DOACs had a lower proportional incidence of bleeding complications in general and an even lower incidence of intracranial haemorrhage than in patients under VKAs.

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