Direct Oral Anticoagulants Versus Warfarin in the Treatment of Left Ventricular Thrombus

Background Use of direct oral anticoagulants (DOACs) for the treatment of left ventricular (LV) thrombus has gained considerable interest. Objective We aimed to evaluate if DOACs are effective in the treatment of LV thrombus compared with warfarin. Methods We evaluated the medical records of patients diagnosed with a new LV thrombus at a tertiary medical center. The primary outcome was the composite of thrombus persistence, stroke, or systemic embolism. We adjusted for potential confounders using multiple logistic regression. The safety outcome was the composite of hemorrhagic stroke or bleeding requiring blood transfusion. Results A total of 129 patients were treated with warfarin and 22, with a DOAC. In unadjusted analysis, 54.3% of patients treated with warfarin met criteria for the efficacy outcome as compared with 40.9% of patients treated with a DOAC ( P = 0.25). In adjusted analysis, no difference between groups was observed (odds ratio = 0.39; 95% CI = 0.14-1.06; P = 0.07 for DOAC vs warfarin). In all, 3.9% of patients treated with warfarin met safety criteria as compared with 4.5% of patients treated with a DOAC. A total of 8 patients in the warfarin group had a stroke or systemic embolism as compared with 0 patients in the DOAC group ( P = 0.37). Conclusion and Relevance Our data suggest that DOACs may be reasonable alternatives for treatment of LV thrombus. When added to the totality of available studies, this study demonstrates that the effectiveness of DOACs in LV thrombus remains uncertain. Randomized clinical trials are needed.

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

European Heart Journal ◽

10.1093/ehjci/ehaa946.1545 ◽

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

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Dabigatran after Short Heparin Anticoagulation for Acute Intermediate-Risk Pulmonary Embolism: Rationale and Design of the Single-Arm PEITHO-2 Study

Thrombosis and Haemostasis ◽

10.1160/th17-06-0434 ◽

2017 ◽

Vol 117 (12) ◽

pp. 2425-2434 ◽

Cited By ~ 4

Author(s):

Frederikus Klok ◽

Walter Ageno ◽

Stefano Barco ◽

Harald Binder ◽

Benjamin Brenner ◽

...

Keyword(s):

Pulmonary Embolism ◽

Venous Thromboembolism ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Phase Iii ◽

Thrombin Inhibitor ◽

Intermediate Risk ◽

Safety Outcome ◽

Efficacy Outcome ◽

Heparin Anticoagulation

AbstractPatients with intermediate-risk pulmonary embolism (PE) may, depending on the method and cut-off values used for definition, account for up to 60% of all patients with PE and have an 8% or higher risk of short-term adverse outcome. Although four non-vitamin K-dependent direct oral anticoagulants (NOACs) have been approved for the treatment of venous thromboembolism, their safety and efficacy as well as the optimal anticoagulation regimen using these drugs have not been systematically investigated in intermediate-risk PE. Moreover, it remains unknown how many patients with intermediate-high-risk and intermediate-low-risk PE were included in most of the phase III NOAC trials. The ongoing Pulmonary Embolism International Thrombolysis 2 (PEITHO-2) study is a prospective, multicentre, multinational, single-arm trial investigating whether treatment of acute intermediate-risk PE with parenteral heparin anticoagulation over the first 72 hours, followed by the direct oral thrombin inhibitor dabigatran over 6 months, is effective and safe. The primary efficacy outcome is recurrent symptomatic venous thromboembolism or death related to PE within the first 6 months. The primary safety outcome is major bleeding as defined by the International Society on Thrombosis and Haemostasis. Secondary outcomes include all-cause mortality, the overall duration of hospital stay (index event and repeated hospitalizations) and the temporal pattern of recovery of right ventricular function over the 6-month follow-up period. By applying and evaluating a contemporary risk-tailored treatment strategy for acute PE, PEITHO-2 will implement the recommendations of current guidelines and contribute to their further evolution.

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The risk of bleeding minimization with direct oral anticoagulants

Atherothrombosis Journal ◽

10.21518/2307-1109-2021-11-1-106-126 ◽

2021 ◽

pp. 106-126

Author(s):

Т. N. Novikova

Keyword(s):

Atrial Fibrillation ◽

Clinical Trials ◽

Anticoagulant Therapy ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Blood Analysis ◽

Systemic Embolism ◽

Risk Of Bleeding ◽

Wide Range

This review is devoted to the safety issues of anticoagulant therapy prescribed for the prevention of stroke and systemic embolism in patients with atrial fibrillation. Direct oral anticoagulants are considered worldwide in accordance with the guidelines for the diagnosis and treatment of atrial fibrillation as the preferred anticoagulant choice for the prevention of stroke and systemic embolism. Direct oral anticoagulants in comparison with vitamin K antagonists generally have similar efficacy, but different safety profiles, primarily, this concerns the risk of large extracranial and, primarily, gastrointestinal hemorrhages. To minimize the risk of bleeding during therapy with direct oral anticoagulants, an individual approach to the choice of the drug for each individual patient is required after assessing the risk of bleeding, searching for a potential bleeding substrate, correcting existing risk factors and eliminating, if possible, the substrate. When choosing an anticoagulant therapy, special attention should be paid to the most vulnerable categories of patients, such as patients of older age groups and patients with concomitant chronic kidney disease. Among the direct oral anticoagulants registered in the Russian Federation, according to meta-analyzes of key randomized clinical trials and real clinical trials, apixaban has the most optimal benefit: risk ratio in a wide range of patients, including vulnerable populations. Dynamic observation, including regular assessment of renal function, control of clinical blood analysis, erythrocyte and platelet levels, after prescribing an individually selected anticoagulant to the patient, ensures the maximum safety of therapy. Small, so-called, annoying bleeding is not a reason for canceling the anticoagulant, but requires a careful search for the causes of bleeding and their correction.

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Elderly Patients with Atrial Fibrillation: Focus on Comorbidity and Safety of Anticoagulant Therapy

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2019-15-4-553-557 ◽

2019 ◽

Vol 15 (4) ◽

pp. 553-557 ◽

Cited By ~ 1

Author(s):

D. A. Napalkov ◽

A. A. Sokolova

Keyword(s):

Atrial Fibrillation ◽

Elderly Patients ◽

Anticoagulant Therapy ◽

Safety Profile ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Systemic Embolism ◽

Good Adherence ◽

Younger Patients

The article discusses issues related to the prescription of anticoagulant therapy to elderly patients with atrial fibrillation (AF), especially those over 70 and 80 years of age. The relevance of the issue is primarily due to the prevalence of AF in this cohort of patients, and the second is due to the higher incidence of comorbidity. The presented material demonstrates the peculiarities of anticoagulant therapy application in groups of patients older than 75, based on the data of randomized clinical trials, and also presents extrapolation of the results of RCTs to the real clinical practice (data of registers and cohort trials). The use of unreasonably low doses of oral anticoagulants in elderly patients is debated. It often leads to a decrease in the efficacy of anticoagulant therapy without improving the drugs safety profile. A new validated scale (ABH) for evaluating of anticoagulant therapy safety is presented in the article. The ABH scale can be used before prescribing to patients exactly direct oral anticoagulants. This scale is simpler and more practical than the HAS-BLED scale. The data for the ABH scale are validated based on direct oral anticoagulants in 21,248 patients from the Norwegian register. The presented results demonstrate a favorable efficiency and safety profile of rivaroxaban in comparison with warfarin in patients 75 years and older. Thus, the overall benefit for the use of rivaroxaban against warfarin in patients > 75 years of age in the subanalysis of the ROCKET-AF study was statistically significantly greater than in younger patients with AF. Data on 11121 patients with AF who were treated with rivaroxaban for the prevention of stroke and systemic embolism are included in the combined analysis of the XANTUS, XANAP and XANTUS-EL registers. 96% of patients in the study did not have serious thromboembolic events. The amount of major bleeding was 1.7 per 100 patient-years, and gastrointestinal bleeding was 0.7 per 100 patient-years. This turned out to be less than in some other registry studies. In addition, patients showed good adherence to rivaroxaban treatment: after a year, 77.4% of patients continued to take the drug.

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Efficacy of direct oral anticoagulants on the resolution of left ventricular thrombus—A case series and literature review

JRSM Cardiovascular Disease ◽

10.1177/2048004019839548 ◽

2019 ◽

Vol 8 ◽

pp. 204800401983954 ◽

Cited By ~ 3

Author(s):

Reem A Bahmaid ◽

Shoroq Ammar ◽

Sarah Al-Subaie ◽

Mohammed A Soofi ◽

Hassan Mhish ◽

...

Keyword(s):

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Case Series ◽

Left Ventricular ◽

Left Ventricular Thrombus ◽

Efficacy And Safety ◽

Ventricular Thrombus ◽

Institutional Review ◽

Medical City

Background Left ventricular thrombus is a frequent complication of acute myocardial infarction and a risk factor for thromboembolic complications. Warfarin has been frequently used, but has some disadvantages that limit its use. Direct oral anticoagulants, in particular Dabigatran and Rivaroxaban have been proved to be effective in preventing thromboembolism among patients with non-valvular atrial ﬁbrillation. However, no randomized clinical trials testing the efficacy and safety of these agents in patients with existing left ventricular thrombus. Furthermore, direct oral anticoagulants are still not approved by the Food and Drug Administration in the management of left ventricular thrombus. Method This study was a retrospective cohort assessing the efficacy of direct oral anticoagulants (Dabigatran or Rivaroxaban) on the resolution of left ventricular thrombus in patients taking either of these drugs during the study period from December, 2011 to December, 2016 at King Fahad Medical City. All patients’ records were reviewed and all patients who were diagnosed with left ventricular thrombus were included. Patients without available echocardiogram records were excluded. The study was approved by the institutional review board of King Fahad medical city, Riyadh Saudi Arabia. Result During the defined study period we found that 413 and 1218 patients were taking Dabigatran and Rivaroxaban, respectively. After filtering them based on the specialty of the prescriber, we ended up with 299 patients who have been started on Dabigatran and 448 patients who have been started on Rivaroxaban by cardiologists. Moreover, after reviewing echocardiogram reports for all of them (747 patients), we found that 11 patients were diagnosed to have left ventricular thrombus. Among those 11 patients, seven of them were treated with direct oral anticoagulants from the beginning and the remaining four patients were shifted from Warfarin to direct oral anticoagulants. All of them (7 patients) showed left ventricular thrombus resolution on follow-up echocardiogram. Conclusion Use of direct oral anticoagulants showed promising results in the resolution of left ventricular thrombus in patients diagnosed with left ventricular thrombus. Further studies at multiple health care centers are needed to further evaluate the efficacy and safety of direct oral anticoagulants as compared to traditional treatment in patients with left ventricular thrombus.

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Left Ventricular Thrombus Therapy With Direct Oral Anticoagulants Versus Vitamin K Antagonists: A Systematic Review and Meta-Analysis

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420977567 ◽

2020 ◽

pp. 107424842097756

Author(s):

Carolina Saleiro ◽

João Lopes ◽

Diana De Campos ◽

Luís Puga ◽

Marco Costa ◽

...

Keyword(s):

Systematic Review ◽

Vitamin K ◽

Meta Analysis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Left Ventricular ◽

Systemic Embolism ◽

Bleeding Events ◽

Ventricular Thrombus

Background: Current guidelines recommend vitamin K antagonists (VKAs) for left ventricular thrombus (LVT) resolution. Direct oral anticoagulants (DOACs) are increasingly evaluated as alternatives to the standard of care in anticoagulation. Methods: We performed a systematic review and meta-analysis to assess the use of DOACs vs VKAs for LVT treatment. The occurrence of LVT resolution, systemic embolism (SE) or stroke, and bleeding events were compared during follow-up using random-effects analysis. Results: The 5 included studies were all observational (a total of 828 patients). Of these, 284 patients (34%) were treated with DOACs, and 544 (66%) treated with VKAs. Thrombus resolution was similar for both methods (pooled odds ratio [OR], 0.91; 95% CI, 0.47-1.75; I2 = 63%; P = .78). The incidence of SE or stroke was also similar (pooled OR, 1.59; 95% CI, 0.85-2.97; I2 = 0%; P = .14). Clinically relevant bleeding incidence was similar for both groups (pooled OR, 0.66; 95% CI, 0.31-1.40; I2 = 0%; P = .28), although all bleeding events were less frequent in the DOAC group (pooled OR, 0.49; 95% CI, 0.26-0.90; I2 = 0%; P = .02). Conclusion: Our systematic review and meta-analysis suggests DOACs were as effective as VKAs for LVT resolution, with a similar risk of systemic embolism/stroke and clinically relevant bleeding. These results, obtained from observational studies, are not definitive and hence randomized controlled trials are needed. Nevertheless, our analysis identifies key experimental features required in future studies.

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Prevention of stroke in elderly patients with a trial fibrillation: possibilities of Apixaban

Russian Journal of Geriatric Medicine ◽

10.37586/2686-8636-2-2020-138-146 ◽

2020 ◽

pp. 138-146

Author(s):

N. M. Vorobyeva ◽

O. N. Tkacheva

Keyword(s):

Elderly Patients ◽

Observational Studies ◽

Clinical Characteristics ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Review Article ◽

Systemic Embolism ◽

Consensus Document ◽

Individualize Treatment

In review article, we discuss the opportunity of use of one of the direct oral anticoagulants – apixaban – for prevention of stroke and/or systemic embolism in elderly patients with non-valvular a trial fibrillation. We consider results of randomized clinical trials of apixaban – ARISTOTLE and AVERROES, including the subgroups analysis in patients in the age of ≥75 years and ≥80 years – in ARISTOTLE, ≥75 years and ≥85 years – in AVERROES. These studies have shown that elderly patients had more benefit from apixaban administration than warfarin (in ARISTOTLE) or acetylsalicylic acid (in AVERROES). The results of two retrospective observational studies confirming the favorable profile of apixaban effectiveness and safety in elderly patients with a trial fibrillation in real clinical practice, and the main provisions of the consensus document FORTA, the purpose of which is to individualize treatment of elderly patients based on clinical characteristics of the patient, are also considered.

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Cardiac tamponade from anticoagulant-related spontaneous haemopericardium in a patient with ischaemic cardiomyopathy and heart failure

BMJ Case Reports ◽

10.1136/bcr-2020-238047 ◽

2020 ◽

Vol 13 (12) ◽

pp. e238047

Author(s):

Alicia Lefas ◽

Neil Bodagh ◽

Jiliu Pan ◽

Ali Vazir

Keyword(s):

Heart Failure ◽

Cardiac Tamponade ◽

Ventricular Dysfunction ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Left Ventricular ◽

Heart Failure Therapy ◽

Severe Left Ventricular Dysfunction ◽

Ischaemic Cardiomyopathy ◽

Common Causes

We describe the case of an 86-year-old man with a background of severe left ventricular dysfunction and ischaemic cardiomyopathy who, having been optimised for heart failure therapy in hospital, unexpectedly deteriorated again with hypotension and progressive renal failure over the course of 2 days. Common causes of decompensation were ruled out and a bedside echocardiogram unexpectedly diagnosed new pericardial effusion with tamponade physiology. The patient underwent urgent pericardiocentesis and 890 mL of haemorrhagic fluid was drained. Common causes for haemopericardium were ruled out, and the spontaneous haemopericardium was thought to be related to introduction of rivaroxaban anticoagulation. The patient made a full recovery and was well 2 months following discharge. This case highlights the challenges of diagnosing cardiac tamponade in the presence of more common disorders that share similar non-specific clinical features. In addition, this case adds to growing evidence that therapy with direct oral anticoagulants can be complicated by spontaneous haemopericardium, especially when coadministered with other agents that affect clotting, renal dysfunction and cytochrome P3A5 inhibitors.

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