Specificities of Approaches to Anticoagulant Therapy in Comorbid Patients with Atrial Fibrillation, Diabetes Mellitus and Impaired Kidney Function

Comorbid patients with atrial fibrillation, diabetes mellitus and chronic kidney disease are at high risk of stroke. The direct oral anticoagulants are indicated for them. The choice of a drug should be based on the results of randomized clinical trials, in which the patients profile corresponds to that in the real Russian clinical practice as much as possible. Taking into account the peculiarities of comorbidity in this category of patients, the requirements for their protection should be considered comprehensively. Along with the prevention of thromboembolic complications, it is necessary that the selected direct oral anticoagulant provides a reduction in the risk of cardiovascular complications, which are typical of diabetes mellitus, and slows down the progression of renal filtration function decline. Rivaroxaban may meet these requirements; its use has significant advantage in high adherence to therapy.

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A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index

Journal of Clinical Medicine ◽

10.3390/jcm10132924 ◽

2021 ◽

Vol 10 (13) ◽

pp. 2924

Author(s):

Domenico Acanfora ◽

Marco Matteo Ciccone ◽

Valentina Carlomagno ◽

Pietro Scicchitano ◽

Chiara Acanfora ◽

...

Keyword(s):

Diabetes Mellitus ◽

Atrial Fibrillation ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Risk Index ◽

Direct Oral Anticoagulants ◽

Anticoagulation Therapy ◽

Efficacy Rate ◽

Cochrane Central Register ◽

Efficacy And Safety

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

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Recommendations on the Use of Non-Vitamin K Antagonist Oral Anticoagulants in Patients with Atrial Fibrillation (Based on 2018 European Heart Rhythm Association Practical Guide)

Kardiologiia ◽

10.18087/cardio.2019.5.2633 ◽

2019 ◽

Vol 59 (5) ◽

pp. 68-79

Author(s):

L. V. Popova ◽

T. B. Kondratieva ◽

M. B. Aksenova ◽

T. V. Khlevchuk ◽

M. Z. Kanevskaya

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Heart Rhythm ◽

Vitamin K Antagonist ◽

Advanced Liver Disease ◽

Clinical Variants

Non-vitamin K antagonist oral anticoagulants (NOACs) – direct oral anticoagulants – are getting the ever-broadening use in clinical practice. However, many problems related to optimal use of NOACs in specific clinical situations remain unresolved. European Heart Rhythm Association in April 2018 issued the renovated recommendations on the use of NOACs in patients with atrial fibrillation. The authors of recommendations presented some specific clinical variants for which they formulated practical advices based on the evidence obtained in randomized clinical trials. They also outlined the indications for use of NOACs, formulated practical start-program and scheme of subsequent follow-up management of patients taking NOACs. Recommendations contain information on pharmacokinetics of NOACs and their interactions with other drugs, consideration of feasibility of NOACs use in patients with chronic renal insufficiency or advanced liver disease. Many other practical problems are covered as well.

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Direct Oral Anticoagulants in Atrial Fibrillation Patients With Concomitant Hyperthyroidism

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa050 ◽

2020 ◽

Vol 105 (9) ◽

pp. 2893-2904

Author(s):

Yi-Hsin Chan ◽

Lung-Sheng Wu ◽

Lai-Chu See ◽

Jia-Rou Liu ◽

Shang-Hung Chang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Lower Risk ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Study Groups ◽

Research Database ◽

Nonvalvular Atrial Fibrillation ◽

Asian Patients

Abstract Objective Patients with hyperthyroidism were excluded from the randomized clinical trials of direct oral anticoagulants (DOACs) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). Methods We performed a nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database. We enrolled 3213 and 1181 NVAF patients with hyperthyroidism who were taking DOACs and warfarin, respectively, from June 1, 2012 to December 31, 2017. We also enrolled 53 591 and 16 564 NVAF patients without hyperthyroidism, taking DOACs and warfarin, respectively. We used propensity score stabilized weights (PSSWs) to balance covariates across the study groups. We also used 1:4 matching on both taking DOACs, with (n = 3213) and without hyperthyroidism (n = 12 852); and both taking warfarin, with (n = 1181) and without hyperthyroidism (n = 4724). Results After PSSW, DOAC had a comparable risk of ischemic stroke/systemic embolism (IS/SE) and a lower risk of major bleeding (hazard ratio [HR] 0.65; 95% confidential interval [CI], 0.44–0.96; P = 0.0295) than warfarin among patients with hyperthyroidism. There were comparable risks of IS/SE and major bleeding between those patients with and without hyperthyroidism. However, among patients taking warfarin, those with hyperthyroidism had a lower risk of IS/SE than those without hyperthyroidism (HR 0.61; 95% CI, 0.43–0.86; P = 0.0050). Conclusion Among NVAF Asian patients with concomitant hyperthyroidism, DOACs may be an effective and safer alternative to warfarin. Thromboprophylaxis with DOACs may be considered for such patients, and it is important to validate this finding in further prospective study.

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Comparative Analysis of Antithrombotic Therapy in In-Patients with Atrial Fibrillation

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2019-15-1-49-53 ◽

2019 ◽

Vol 15 (1) ◽

pp. 49-53

Author(s):

V. I. Petrov ◽

O. V. Shatalova ◽

A. S. Gerasimenko ◽

V. S. Gorbatenko

Keyword(s):

Atrial Fibrillation ◽

High Risk ◽

Anticoagulant Therapy ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Thromboembolic Complications ◽

Antithrombotic Agents ◽

Cardiology Department ◽

Number Of Patients

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.

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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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The role of edoxaban in preventing thromboembolic complications in patients with atrial fibrillation

Atherothrombosis Journal ◽

10.21518/2307-1109-2020-2-28-43 ◽

2020 ◽

pp. 28-43

Author(s):

O. O. Shakhmatova

Keyword(s):

Atrial Fibrillation ◽

Drug Interactions ◽

Dose Reduction ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Factor Xa ◽

Extensive Study ◽

Thromboembolic Complications ◽

Nonvalvular Atrial Fibrillation ◽

Life Threatening

Edoxaban is a selective direct factor Xa inhibitor. Edoxaban in a dose of 60 mg per day is an effective and safe option in the prevention of thromboembolic complications in patients with nonvalvular atrial fibrillation, including in combination therapy in patients after percutaneous coronary interventions. ENGAGE AF-TIMI 48 is currently the most extensive study comparing direct oral anticoagulants and warfarin in patients with atrial fibrillation, both in terms of number of participants and duration of observation. For edoxaban, an adequate approach to dose reduction has been developed in patients with alikely increase in plasma concentration due to renal impairment, low body weight or inter-drug interactions. Such dose reduction does notlead to an increase in the frequency of ischemic complications.Edoxaban is characterized by an optimal safety profile in patients with chronic moderate kidney disease, a small number of drug interactions and a convenient mode of administration. In patients with atrial fibrillation and concomitant ischemic heart disease, the use of Edoxaban is associated with a decrease in the frequency of myocardial infarctions, as well as strokes and episodes of systemic thromboembolism in comparison with warfarin. The drug can be successfully used as anticoagulant support for cardioversion and catheter ablation for atrial fibrillation.Edoxaban intake does not require routinelaboratory control. In case of unexpected situations (life-threatening bleeding, urgent surgical intervention) in patients receiving edoxaban, to assess the degree of anticoagulation should use the determination of anti-Xa activity. Clinical studies of a specific antidote of edoxaban - andexanet alfa are ongoing. Before approval of the specific antidote in severe andlife-threatening bleedings against the background of edoxaban administration, the use of prothrombin complex concentrate should be considered. Data on the effective and safe use of edoxaban in routine clinical practice have been accumulated.

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Comparative efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease

Kardiologiia ◽

10.18087/cardio.2020.9.n1178 ◽

2020 ◽

Vol 60 (9) ◽

pp. 102-109

Author(s):

V. S. Gorbatenko ◽

A. S. Gerasimenko ◽

O. V. Shatalova

Keyword(s):

Atrial Fibrillation ◽

Relative Risk ◽

Creatinine Clearance ◽

Randomized Clinical Trials ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Indirect Comparison ◽

Efficacy And Safety ◽

Comparative Efficacy ◽

Nonvalvular Atrial Fibrillation

Aim To compare efficacy and safety of direct oral anticoagulants (DOACs) for prevention of stroke in patients with nonvalvular atrial fibrillation and reduced creatinine clearance.Material and methods Systematic search for literature and indirect comparison of DOACs were performed.Results The indirect comparison included five randomized clinical trials. The DOACs were comparable by the efficacy of preventing stroke and systemic embolism. The safety profiles had differences. Apixaban significantly decreased the relative risk of major bleeding compared to rivaroxaban by 27 % (relative risk (RR) 0.73; 95 % confidence interval (CI): 0.55–0.98). The apixaban advantage was even greater in the group of patients with a creatinine clearance <50 ml/min: RR was reduced by 48 % compared to rivaroxaban (RR=0.52; 95 % CI: 0.32–0.84), by 50 % compared to dabigatran 300 mg/day (RR=0.50; 95 % CI: 0.31–0.81), and by 48 % compared to dabigatran 220 mg/day (RR=0.52; 95 % CI: 0.32–0.85)Conclusion The indirect comparison of DOACs showed that their efficacy was comparable. With respect of safety, apixaban is the preferrable DOAC for patients with atrial fibrillation and creatinine clearance below 50 ml/min.

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Personalized approach for direct oral anticoagulant prescription: from theory to practice

Terapevticheskii arkhiv ◽

10.26442/00403660.2019.07.000045 ◽

2019 ◽

Vol 91 (7) ◽

pp. 111-120

Author(s):

A I Skripka ◽

V V Kogay ◽

A I Listratov ◽

A A Sokolova ◽

D A Napalkov ◽

...

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulant ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Direct Oral Anticoagulant ◽

Efficacy And Safety ◽

Future Perspectives ◽

Theory To Practice ◽

Personalized Approach

Data on possibilities of personalized approach for direct oral anticoagulants (DOAC) choice in patients with atrial fibrillation are presented in the article. We also review clinical and fundamental studies and future perspectives on pharmacogenetic and pharmacokinetic tests to predict the efficacy and safety of DOAC.

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Algorithm for the Choice of Anticoagulant for Patients with Atrial Fibrillation

Rational Pharmacotherapy in Cardiology ◽

10.20996/1819-6446-2020-04-16 ◽

2020 ◽

Vol 16 (2) ◽

pp. 199-205 ◽

Cited By ~ 1

Author(s):

Yu. P. Skirdenko ◽

N. A. Nikolaev

Keyword(s):

Atrial Fibrillation ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Food Preferences ◽

Antiplatelet Agents ◽

Thromboembolic Complications ◽

Adherence To Treatment ◽

Treatment Optimization ◽

Initial Examination ◽

Hemorrhagic Complications

Aim. To evaluate the effectiveness of the anticoagulant choice algorithm in the prevention of complications of atrial fibrillation (AF). Material and methods. Patients with AF (n=98) were included into observational prospective study. The level of adherence to treatment, risk of food interactions and presence of CYP2C9 and VKORC1 genes mutations were determined at the initial examination. These indicators were necessary to specify an eligible anticoagulant according to the evaluated algorithm. Therapy was prescribed by the attending physician. Hemorrhagic and thromboembolic complications were assessed at the next examination after 24 weeks. Results. Hemorrhagic complications were observed in 31.6% of patients during the follow-up. Their number was comparable in individuals taking antiplatelet agents and direct oral anticoagulants (DOACs) (χ2=1.44; p<0.49, Pearson) and significantly more in individuals taking warfarin (as compared to DOACs: χ2=25.08; p<0.000, Pearson; and antiplatelet agents: χ2=34.32; p<0.000, Pearson). Thromboembolic complications were reported in 8.16% of patients. Their number was more in patients taking DOACs than warfarin (χ2=7.03; p<0.03, Pearson). Patients who had to take DOACs according to the algorithm, but in the study took warfarin, demonstrated significantly greater number of thromboembolic complications, with a comparable number of hemorrhagic complications. Patients who could take warfarin according to the algorithm, but in the study took DOACs, had significantly greater number of thromboembolic complications, with a comparable number of hemorrhagic complications. Conclusion. The results of the study demonstrated the potential for reduction in complications, especially thromboembolic, in the choice of anticoagulant using the algorithm; and reduction in complications of therapy, primarily with warfarin, due to the initial prescription of DOACs. The proposed approach, which consists in using the quantitative assessment of adherence to treatment, and only if necessary supplemented by the assessment of food preferences and/or pharmacogenetic studies, contributes to the treatment optimization.

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Direct Oral Anticoagulants after Ischemic Stroke: Which Patient? Which Drug? And How Early?

Hämostaseologie ◽

10.1055/a-1329-2523 ◽

2021 ◽

Vol 41 (01) ◽

pp. 031-034

Author(s):

Gian Marco De Marchis

Keyword(s):

Atrial Fibrillation ◽

Clinical Trials ◽

Ischemic Stroke ◽

Vitamin K ◽

Randomized Clinical Trials ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Reversal Agents

AbstractDirect oral anticoagulants (DOACs) are recommended over vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and ischemic stroke. The main advantage of DOAC over VKA is the lower rate of bleeding and mortality. This review covers challenges clinicians can encounter when treating patients with AF and ischemic stroke, including timing of DOAC start and ongoing randomized clinical trials, appropriate dosing, and available comparative evidence across DOACs. For patients without AF but with an ischemic stroke, the review outlines the role of DOACs. Finally, the risk of thrombotic events associated with specific DOAC reversal agents and DOAC pausing is reviewed.

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