ANTICOAGULANT THERAPY IN CANCER PATIENTS WITH ATRIAL FIBRILLATION. CONSIDERING AGE FACTOR

Author(s):  
В. И. Потиевская ◽  
А. А. Ахобеков ◽  
М. Ф. Баллюзек

Рассматривается современное состояние вопроса выбора антикоагулянтной терапии при фибрилляции предсердий (ФП) у онкологических больных. Отмечается, что сложность выбора антикоагулянта при злокачественных новообразованиях (ЗНО) определяется такими факторами, как коморбидные сердечно-сосудистые заболевания, нарушения функции печени и почек, метаболические дисфункции, свойственные, прежде всего, пациентам старшей возрастной группы. Приводятся актуальные данные по оценке риска геморрагических и тромбоэмболических осложнений ФП при ЗНО в аспекте возраста. Обсуждаются возможные причины увеличения риска развития ФП во время и после лечения ЗНО, в том числе и в связи с возраст-ассоциированностью этих патологий. Рассмотрены вопросы выбора антикоагулянтов у пациентов, находящихся на активной противоопухолевой терапии, особенно на препаратах из группы прямых оральных антикоагулянтов (ПОАК). Согласно данным обсервационных исследований, именно ПОАК являются перспективным, относительно безопасным и эффективным выбором для онкологических пациентов с ФП, в связи с чем их применение должно активно изучаться в рандомизированных клинических исследованиях с учетом фактора возраста. Подчеркивается, что подбор схемы антикоагулянтной терапии у пациентов с ФП и ЗНО требует междисциплинарного участия кардиологов и онкологов, а часто и гериатров, чтобы индивидуализировать лечение и предложить наиболее эффективную терапию. The current issue of the choice of anticoagulant therapy of atrial fibrillation (AF) in cancer patients is considered. It is noted that the difficulty of choosing an anticoagulant in malignancies is largely determined by age-related factors, such as comorbid cardiovascular diseases, liver and kidney dysfunction, metabolic disorders common for in elderly patients. Current data on the risk assessment of hemorrhagic and thromboembolic complications of AF in cancer patients in the aspect of age presented. During and after cancer treatment, the risk of developing AF can increase, also in connection with the age-associated pathology. Possible reasons of it are discussed. The choice of different anticoagulants groups in patients treated with anticancer therapy, including direct oral anticoagulants (DOAC) is considered. According to available data from observational studies, it is the DOAC that is a promising, relatively safe and effective choice for cancer patients with AF, and therefore their use should be actively studied in randomized trials, considering the factor of age. It is particularly noted that solving this problem requires the interdisciplinary involvement of cardiologists, oncologists, and sometimes, geriatrics, to individualize treatment for each case and to offer the most effective therapy.

2020 ◽  
Vol 25 (11) ◽  
pp. 4175
Author(s):  
Zh. D. Kobalava ◽  
P. V. Lazarev ◽  
M. V. Vatsik

Atrial fibrillation (AF) and chronic kidney disease (CKD) are common and interrelated diseases, the combination of which is associated with a poor prognosis. The efficacy and safety of direct oral anticoagulants (DOACs) used to prevent thromboembolic complications of AF may depend on renal function due to the specific pharmacokinetics of these drugs. This review considers current data on the role of kidneys in the pathogenesis of ischemic and bleeding events, methods of renal function assessment and related classification issues, as well as comparison of warfarin and DOAC therapy, in patients with AF and renal dysfunction of different stages based on the results of randomized controlled trials and actual clinical practice. DOAC use in the context of dynamic deterioration of renal function, supranormal renal function, and their effect on renal outcomes is discussed. International guidelines on anticoagulant therapy in AF and renal dysfunction were analyzed.


Kardiologiia ◽  
2021 ◽  
Vol 61 (10) ◽  
pp. 81-88
Author(s):  
T. N. Novikova

This review focuses on issues of anticoagulant therapy in patients with atrial fibrillation (AF) associated with chronic kidney disease (CKD). Such patients are at high risk of stroke whereas the choice of an anticoagulant is difficult. A wealth of information about a negative effect of warfarin on the kidney function has accumulated. A need for an alternative therapy to warfarin for patients with stage 3-4 CKD has become imminent. In this regard, rivaroxaban seems to be an appropriate replacement for warfarin in such patients. In randomized, controlled studies that evaluated the efficacy of direct oral anticoagulants in comparison with warfarin, the efficacy and safety profile of a “kidney” dose in moderate disorders of kidney function has been studied only for rivaroxaban. Moreover, both randomized, controlled studies and studies performed in the conditions of clinical practice, have demonstrated a more favorable effect of rivaroxaban on kidney function compared to warfarin. Patients with AF associated with CKD require a comprehensive protection, which, according to results of clinical studies, may be provided by rivaroxaban. 


Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Shirin Ardeshirrouhanifard ◽  
Huijun An ◽  
Ravi Goyal ◽  
Mukaila Raji ◽  
Caleb Alexander ◽  
...  

Objective: Post-hoc analysis of three pivotal clinical trials suggests no difference in risk of ischemic stroke or systemic embolism among cancer patients with atrial fibrillation treated with direct oral anticoagulants (DOACs) vs. warfarin. However, these studies were underpowered and also do not reflect the context of real-world use. We compared the effectiveness of DOACs versus warfarin for the risk of stroke or systemic embolism and all-cause death in patients with NVAF. Methods: We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2009 to 2016 and included patients aged ≥66 years diagnosed with cancer (breast, bladder, colorectal, esophagus, lung, ovary, kidney, pancreas, prostate, stomach or uterus) and NVAF. We limited the cohort to patients who newly initiated warfarin or DOACs (from 2010 to 2016) with no history of ischemic stroke or systemic embolism. The primary outcome was hospitalization due to ischemic stroke or systemic embolism and the secondary outcome was all-cause death. We used Fine and Gray’s competing risk model, while treating death as a competing risk, to determine the association of oral anticoagulants with the incidence of stroke or systemic embolism. We also adjusted the analysis using inverse probability of treatment weighted (IPTW). Additionally, an IPTW-adjusted Cox proportional hazards regression model was constructed for all-cause death. Results: Of 1,028,784 patients with cancer, 158,744 (15.4%) were diagnosed with atrial fibrillation. After applying all inclusion criteria, the final study cohort included 7,334 cancer patients diagnosed with incident NVAF who newly initiated warfarin or DOACs, of which 3,194 (43.6%) used warfarin and 4,140 (56.4%) used DOACs. The unadjusted rate of stroke or systemic embolism was similar among warfarin and DOACs users (1.20 vs. 1.32 cases per 100 person-years, p=0.27). In the IPTW weighted competing risk model, the use of DOACs was not associated with an increased risk of stroke or systemic embolism compared with warfarin users (Hazard Ratio [HR] 1.41, 95% confidence intervals [CI] 0.90-2.20). However, DOACs users had a significantly lower risk of all-cause death compared with warfarin users (HR 0.82, CI 0.74-0.91). Conclusion: Among cancer patients diagnosed with NVAF, DOACs had a similar risk for stroke or systemic embolism compared to warfarin, although DOAC use was associated with reduced risk of all-cause mortality.


2019 ◽  
Vol 15 (1) ◽  
pp. 49-53
Author(s):  
V. I. Petrov ◽  
O. V. Shatalova ◽  
A. S. Gerasimenko ◽  
V. S. Gorbatenko

Aim. To study the frequency of prescribing antithrombotic agents in patients with non-valvular atrial fibrillation (AF) who were hospitalized in the cardiology department of a multidisciplinary hospital.Material and methods. A retrospective one-time study of medical records of 765 patients with non-valvular AF treated in the cardiology department of a multidisciplinary hospital in 2012 and 2016 was performed.Results. All patients were stratified in three groups depending on the CHA2DS2-VASc score. The frequency of prescribing antithrombotic agents was evaluated in each group. A low risk of thromboembolic complications was found in 1% (n=3) of patients in 2012 and 0.6% (n=3) in 2016. All these patients received antithrombotic agents. CHA2DS2-VASc=1 was found in 6% (n=15) of patients with AF in 2012 and in 3.4% (n=17) in 2016. A significant number of patients in this group received anticoagulant therapy with vitamin K antagonists (warfarin) or with direct oral anticoagulants. A high risk of thromboembolic complications (CHA2DS2-VASc≥2) was found in 93% of patient (n=245) in 2012 and in 96% (n=482) in 2016. Anticoagulant therapy was prescribed in 70.2% (n=172) patients with high risk in 2012 and 80% (n=387) in 2016. However, some patients with high risk of thromboembolic complications did not have the necessary therapy.Conclusion. Positive changes in the structure and frequency of prescribing anticoagulant drugs in patients with AF and a high risk of thromboembolic complications were found during the years studied. 


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Dana Prídavková ◽  
Matej Samoš ◽  
Tomáš Bolek ◽  
Ingrid Škorňová ◽  
Jana Žolková ◽  
...  

Type 2 diabetes (T2D) is an independent risk factor of stroke and systemic embolism in patients with atrial fibrillation (AF), and T2D patients with AF-associated stroke seem to have worse clinical outcome and higher risk of unfavorable clinical course compared to individuals without this metabolic disorder. Long-term anticoagulation is indicated in majority of T2D patients with AF to prevent adverse AF-associated embolic events. Direct oral anticoagulants (DOACs), direct oral thrombin inhibitor dabigatran, and direct oral factor Xa inhibitors, rivaroxaban, apixaban, and edoxaban, have emerged as a preferred choice for long-term prevention of stroke in AF patients offering potent and predictable anticoagulation and a favorable pharmacology with low risk of interactions. This article reviews the current data regarding the use of DOACs in individuals with T2D and AF.


2017 ◽  
Vol 117 (02) ◽  
pp. 219-230 ◽  
Author(s):  
Cihan Ay ◽  
Ingrid Pabinger ◽  
Alexander T. Cohen

SummaryVenous thromboembolism (VTE) is a significant health problem in the general population but especially in cancer patients. In this review, we discuss the epidemiology and burden of the disease, the pathophysiology of cancer-associated VTE, and the clinical treatment options for both primary prevention and acute treatment. Overall, the development of VTE in cancer patients is related to increases in morbidity, mortality, and medical costs. However, the incidence of cancer-associated VTE varies due to patient-related factors (e.g. thrombophilia, comorbidities, performance status, history of venous diseases), tumour-related factors (e.g. cancer site, stage, grade), and treatment-related factors (e.g. surgery, chemotherapy, anti-angiogenesis treatment, hormonal and supportive treatment). Furthermore, blood count parameters (e.g. platelets and leukocytes) and biomarkers (e.g. soluble P-selectin and D-dimer) are predictive markers for the risk of VTE in cancer patients and have been used to enhance risk stratification. Evidence suggests that cancer itself is associated with a state of hypercoagulability, driven in part by the release of procoagulant factors, such as tissue factor, from malignant tissue as well as by inflammation-driven activation of endothelial cells, platelets, and leukocytes. In general, low-molecular-weight heparin (LWMH) monotherapy is the standard of care for the management of cancer-associated VTE, as vitamin K antagonists are less effective in cancer patients. Direct oral anticoagulants (DOACs) offer a potentially promising treatment option for cancer patients with VTE, but recommendations concerning the routine use of DOACs should await head-to-head studies with LMWH.


2021 ◽  
pp. 106-126
Author(s):  
Т. N. Novikova

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.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 877-877 ◽  
Author(s):  
Surbhi Shah ◽  
Yvonne H Datta ◽  
Faye Norby ◽  
Alvaro Alonso

Abstract Introduction Cancer patients are at high risk for morbidity and mortality due to thrombosis and bleeding, in addition they may also have pre-existing conditions, such as atrial fibrillation (AF) and prior venous thromboembolism (VTE), for which chronic anticoagulation may be indicated. Historically, warfarin was the most commonly prescribed anticoagulant for stroke prevention in AF patients. Since 2010, the US FDA has approved 4 alternative direct oral anticoagulants (DOACs) - dabigatran, rivaroxaban, apixaban, edoxaban to reduce the risk of stroke and systemic embolism in patients with AF. There is limited literature to support the use of DOACs in cancer patients, but they are being prescribed by medical professionals nonetheless. Therefore, additional research is necessary to determine the effectiveness of the DOACs in cancer patients, to quantify their bleeding risks, and to identify patients that are more likely to benefit from these new medications in comparison to warfarin. Large randomized clinical trials of DOACs compared to warfarin in cancer patients have not been performed. Our aim was to determine the effectiveness and associated risk of DOACs vs. warfarin in a large, real-world population of cancer patients with AF. Methods We identified 532,743 AF patients initiating oral anticoagulant use in 2010-2014 continuously enrolled in MarketScan databases. We selected 41,036 cancer patients with inpatient or outpatient ICD9 code 140.x-172.x and 174.x-209.x (excluded 173.x, non-melanoma skin cancer), and then identified a subset of cancer patients being actively treated at the time of anticoagulant initiation. Active cancer patients were defined by the use of chemotherapy, radiation therapy or cancer surgery within 6 months prior to the start of anticoagulation. Patients were categorized according to the first anticoagulant prescribed after AF diagnosis. DOAC users were matched with warfarin users by age (±3 years), sex, enrollment date (90 days), and anticoagulant initiation date (90 days). Study endpoints, including ischemic stroke, severe bleeding (intracranial hemorrhage, gastrointestinal bleeding), other bleeding (genitourinary bleeding, hemopericardium, hemarthrosis, epistaxis, hemoptysis and unspecified hemorrhage) and VTE were identified using inpatient diagnostic codes, and VTE was additionally identified from 2 outpatient diagnostic codes within the same year. Cox proportional hazards models were used to access the association between type of anticoagulant and outcomes adjusting for high-dimensional propensity score, age, sex, CHA2DS2-VASc score, and the prevalent outcome. Results The demographic profile of the patients included in the analysis are depicted in Table 1, and Table 2 summarizes the outcomes data. In this analysis there were 6,075 cancer patients with AF who were on DOACs (rivaroxaban 2808, dabigatran 2189, and apixaban 1078) compared to 10,021 on warfarin, with a mean age of 74 years, and a mean follow-up time of 1 year. Approximately 40% of the patients were woman, and breast cancer was the most common cancer in each cohort. We found that for rivaroxaban and dabigatran users, the adjusted hazard ratios for severe bleeding was non significantly different to warfarin users, however, apixaban users had a lower risk of severe bleeding compared to warfarin users, with a hazard ratio 0.37 (95% confidence interval 0.17-0.79, p=0.01). The risk of other bleeding was lower in dabigatran users compared to warfarin users with a hazard ratio 0.58 (95% confidence interval 0.41-0.84, p=0.003). The risk of ischemic stroke did not differ significantly amongst different anticoagulant users. Each of the DOACs was superior to warfarin in lowering the risk of incident VTE, with p values < 0.0001. Conclusion Based on this analysis the DOACs seem to be well tolerated in cancer patients in regard to the management of atrial fibrillation, with lower or similar rates of bleeding and stroke compared to warfarin users. Importantly, the DOAC users had a significantly lower risk of incident VTE. Given that VTE events contribute to significant morbidity and mortality in cancer patients, prescription of DOACs in place of warfarin can be considered in cancer patients with AF, while we are awaiting prospective data from randomized trials. Disclosures No relevant conflicts of interest to declare.


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