scholarly journals Newer Oral Anticoagulants: Stroke Prevention and Pitfalls

2016 ◽  
Vol 10 (1) ◽  
pp. 94-104 ◽  
Author(s):  
Anand Patel ◽  
Richard P. Goddeau Jr ◽  
Nils Henninger
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulant Effect ◽  
Therapeutic Window ◽  
Thrombin Inhibitor ◽  
Multiple Drug ◽  
Thrombotic Complication ◽  
Narrow Therapeutic Window ◽  
Increased Risk

Warfarin is very effective in preventing stroke in patients with atrial fibrillation. However, its use is limited due to fear of hemorrhagic complications, unpredictable anticoagulant effects related to multiple drug interactions and dietary restrictions, a narrow therapeutic window, frequent difficulty maintaining the anticoagulant effect within a narrow therapeutic window, and the need for inconvenient monitoring. Several newer oral anticoagulants have been approved for primary and secondary prevention of stroke in patients with non-valvular atrial fibrillation. These agents have several advantages relative to warfarin therapy. As a group, these direct oral anticoagulants (DOAC), which include the direct thrombin inhibitor, dabigatran, and the factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban), are more effective than dose adjusted warfarin for prevention of all-cause stroke (including both ischemic and hemorrhagic stroke), and have an overall more favorable safety profile. Nevertheless, an increased risk of gastrointestinal bleeding (with the exception of apixaban), increased risk for thrombotic complication with sudden discontinuation, and inability to accurately assess and reverse anticoagulant effect require consideration prior to therapy initiation, and pose a challenge for decision making in acute stroke therapy.

scholarly journals Type 2 Diabetes, Atrial Fibrillation, and Direct Oral Anticoagulation

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Dana Prídavková ◽  
Matej Samoš ◽  
Tomáš Bolek ◽  
Ingrid Škorňová ◽  
Jana Žolková ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Clinical Course ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Current Data ◽  
Thrombin Inhibitor

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.

scholarly journals Idarucizumab, a Specific Antidote for Dabigatran: Immediate, Complete and Sustained Reversal of Dabigatran Induced Anticoagulation in Elderly and Renally Impaired Subjects

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 344-344 ◽  
Author(s):  
Stephan Glund ◽  
Joachim Stangier ◽  
Michael Schmohl ◽  
Viktoria Moschetti ◽  
Wouter Haazen ◽  
...  
Keyword(s):  
Vitamin K Antagonists ◽  
Dabigatran Etexilate ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Anticoagulant Effect ◽  
Thrombin Time ◽  
Double Blind ◽  
Male And Female ◽  
Increased Risk ◽  
Pharmacologically Active

Abstract Introduction Oral anticoagulation is an effective therapy to prevent and treat thromboembolic events. So far, Vitamin K antagonists have been the main drug of choice. Recently, the advent of the direct oral anticoagulants (DOAC) has changed medical practice significantly; nevertheless all anticoagulants are associated with an increased risk of bleeding. Bleeding management can be achieved through established therapies; however specific antidotes are not yet available for these agents to further facilitate patient management in cases needed. Previously the dabigatran antidote (idarucizumab) has demonstrated immediate, complete and sustained reversal of dabigatran induced anti-coagulation in healthy male volunteers. In the present study it was determined whether and to what extent doses of up to 5 g idarucizumab would reverse the anticoagulant effects of dabigatran in male and female healthy mid-aged, elderly and renally impaired volunteers. In addition, it was tested whether oral intake of dabigatran etexilate 24 hrs after idarucizumab treatment could restore dabigatran related anticoagulation. It was further tested if a second administration of idarucizumab 2 months later was safe and well tolerated. Methods Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of idarucizumab were investigated in a randomized, double-blind, placebo controlled two-way cross-over study in 46 male and female volunteers. Dabigatran etexilate (DE), 220 mg bid in healthy subjects and 150 mg bid in subjects with mild or moderate renal impairment (CLCR60 to <90 or 30 to <60 [mL/min], respectively) was given over 4 days to achieve the steady state conditions. Idarucizumab doses of 1 g, 2.5 g, 5 g or 5 g given as 2x2.5 g one hour apart were administered as 5 min i.v. infusion 2 hrs after the last dose of DE. Concentrations of unbound dabigatran were determined as a measure of pharmacologically active dabigatran. The anticoagulant effect of dabigatran and its reversal were assessed by coagulation time measurements, including diluted Thrombin Time (dTT, Hemoclot® DTI assay), Ecarin Clotting Time (ECT) and activated Partial Thromboplastin Time (aPTT). Results All administered doses of idarucizumab were safe and well tolerated. PK measurements of unbound dabigatran indicated that idarucizumab binding and thus reversal of the anticoagulant effect of dabigatran occurred immediately after end of infusion. Prolongation of clotting times induced by dabigatran was reversed to baseline at the end of the 5 minute infusion of the antidote. This was consistently demonstrated by all clotting assays. Sustained reversal over the entire observation period was observed for idarucizumab doses of 2.5 g, 5 g and 2x2.5 g. For the 1g dose, there was partial return of dabigatran induced anticoagulation around 2-4 hours after i.v. infusion. Also a second administration of idarucizumab (two months after the first) was safe and resulted in complete reversal. In addition, PD and PK measurements at selected time points and in comparison to placebo treatment confirmed that effective dabigatran anticoagulation could be re-established 24 hours after administration of idarucizumab. Conclusions The dabigatran antidote, idarucizumab, was well tolerated under all conditions tested. The administration of 5 g or 2x2.5 g led to sustained reversal of dabigatran induced anticoagulation in male and female subjects of different age and renal function. In addition, idarucizumab administered 2 months apart achieved the same degree of reversal. Dabigatran anticoagulation could be re-established 24 hrs after idarucizumab dosing. These results support the use of a total dose of 5 g idarucizumab as an effective dose in further clinical testing. Disclosures Glund: Boehringer Ingelheim: Employment. Off Label Use: Idarucizumab, a specific antidote for dabigatran, is in clinical development.. Stangier:Boehringer Ingelheim: Employment. Schmohl:Boehringer Ingelheim: Employment. Moschetti:Boehringer Ingelheim: Employment. Haazen:SGS Life Science Services (contracted by Boehringer Ingelheim to conduct the study): Employment. De Smet:SCS Boehringer Ingelheim Comm. V.: Employment. Gansser:Boehringer Ingelheim: Employment. Norris:Boehringer Ingelheim: Employment. Lang:Boehringer Ingelheim: Employment. Reilly:Boehringer Ingelheim: Employment.

scholarly journals Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Renal Dysfunction

2021 ◽  
Vol 17 (1) ◽  
pp. 62-72
Author(s):  
Z. D. Kobalava ◽  
A. A. Shavarov ◽  
M. V. Vatsik-Gorodetskaya
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Disease Epidemiology ◽  
Increased Risk ◽  
Estimate Glomerular Filtration Rate

Atrial fibrillation and renal dysfunction often coexist, each disorder may predispose to the other and contribute to worsening prognosis. Both atrial fibrillation and chronic kidney disease are associated with increased risk of stroke and thromboembolic complications. Oral anticoagulation for stroke prevention is therefore recommended in patients with atrial fibrillation and decreased renal function. Each direct oral anticoagulant has unique pharmacologic properties of which clinician should be aware to optimally manage patients. The doses of direct oral anticoagulants require adjustment for renal function. There is debate regarding which equation, the Chronic Kidney Disease Epidemiology (CKD-EPI) equation vs. the Cockcroft-Gault equation, should be used to estimate glomerular filtration rate in patients with atrial fibrillation treated with direct oral anticoagulants. Our review tries to find arguments for benefit of direct oral anticoagulants in patients with renal dysfunction.

Abstract 15740: Concomitant Use of Dronedarone and Direct Oral Anticoagulants and Risk of Bleeding in Patients With Atrial Fibrillation: An Analysis of the U.S. Truven Health MarketScan Database

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sampada K Gandhi ◽  
Michael D Ezekowitz ◽  
James A Reiffel ◽  
Rania Boiron ◽  
Mattias Wieloch
Keyword(s):  
Atrial Fibrillation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Concomitant Treatment ◽  
Gi Bleeding ◽  
Risk Of Bleeding ◽  
Combined Use ◽  
Increased Risk

Introduction: Dronedarone (DR), a P-gp and CYP 3A4 inhibitor may increase exposure and the risk of bleeding when combined with direct oral anticoagulants (DOACs). Objective: To examine the association between concomitant use of DR and the DOACs, apixaban (A), dabigatran (D), and rivaroxaban (R), and risk of bleeding compared to DOAC monotherapy in patients with atrial fibrillation (AF). Methods: A retrospective cohort study using a U.S. claims database, Truven Health MarketScan identified new users of A, D, and R in patients with AF ≥18 years from Jan 1, 2007 to Sep 30, 2017. Bleeding was defined as hospitalization or emergency room visit with a primary diagnosis of gastrointestinal (GI) bleeding, intracranial hemorrhage (ICH), or bleeding at other sites. Risk of overall and by type of bleeding was examined in concomitant users of DOAC and DR compared to patients using DOAC alone after adjusting for covariates of interest and applying propensity score (PS) trimming via Cox proportional hazards modeling. Results: Among concomitant users of DR and A (1,932), D (3,117), and R (2,395), crude incidence rates of bleeding per 1,000 person-years were 17.2, 37.8, 61.8, respectively versus 26.8, 31.3, and 44.9 in users of A (51,420), D (42,312), and R (57,300) alone. Incidence rates stratified by PS showed higher bleeding incidence in concomitant users of DR with D or R, but not with A. No increased bleeding risk was associated with use of DR and A vs A alone [Adjusted Hazard ratio (aHR): 0.69 (95% CI: 0.40, 1.17), p=0.16]. A modestly increased risk of GI bleeding but not overall bleeding was associated with combined use of DR and D vs D alone [aHR bleeding: 1.18 (95% CI: 0.89, 1.56), p=0.26; aHR GI bleeding: 1.40 (95% CI: 1.01, 1.93); p=0.04]. An increased risk of overall bleeding, driven by GI bleeding, was associated with combined use of DR and R vs R alone [aHR bleeding:1.31 (95% CI: 1.01, 1.69); p=0.04; aHR GI bleeding:1.39 (95% CI: 0.98, 1.95); p=0.06]. There was no increase in the risk of ICH associated with combined use of DR and any DOAC. Conclusions: Concomitant treatment with DR and A showed no increased risk of bleeding, but DR increased the risk of GI bleeding when given with D or R, and of overall bleeding only with R. Concomitant treatment with DR and any DOAC did not increase ICH risk.

scholarly journals Routine Coagulation Tests in Patients With Nonvalvular Atrial Fibrillation Under Dabigatran and Rivaroxaban Therapy: An Affordable and Reliable Strategy?

2019 ◽  
Vol 25 ◽  
pp. 107602961983505 ◽  
Author(s):  
Vanessa M. Silva ◽  
Maurício Scanavacca ◽  
Francisco Darrieux ◽  
Cyrillo Cavalheiro ◽  
Celia C. Strunz
Keyword(s):  
Atrial Fibrillation ◽  
Therapeutic Range ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Screening Tests ◽  
Therapeutic Monitoring ◽  
Thrombin Inhibitor ◽  
Nonvalvular Atrial Fibrillation ◽  
Coagulation Tests ◽  
Routine Coagulation

Dabigatran and rivaroxaban, direct oral anticoagulants (DOACs), affect coagulation tests, and knowledge of their effects is important for therapeutic monitoring. Our aim was to examine the association between DOAC levels and routine coagulation tests in patients with nonvalvular atrial fibrillation. Samples from patients receiving dabigatran (150 mg) and patients receiving rivaroxaban (20 mg) were collected 2 hours after drug intake. Direct oral anticoagulant concentrations were determined using direct Hemoclot thrombin inhibitor (HTI) assay (HTI test) and a direct Xa inhibitor (Anti Xa-Riva). The routine coagulation measured included activated partial thromboplastin time (aPTT) and prothrombin time (PT). The median plasmatic dabigatran was 128.3 ng/mL (95% confidence interval [CI]: 93.7-222.6 ng/mL). The HTI exhibited a good correlation with aPTT ( R2 = 0.74; P < .0001). The median plasmatic rivaroxaban was 223.9 ng/mL (95% CI: 212.3-238.9 ng/mL). Anti-Xa-Riva correlated with PT ( R2 = 0.69, P< .0001) and aPTT (R2 = 0.36, P < .001), but prolonged PT results were obtained, even below the rivaroxaban therapeutic range (20%). The routine coagulation tests were able to identify out of therapeutic range concentrations for dabigatran and rivaroxaban. We suggest the use of these screening tests to better understand and monitor the subtherapeutic concentrations of these DOACs.

scholarly journals Comparison of Effectiveness and Safety of Antiarrhythmic Drugs Class IC and III in Patients After Electrical Cardioversion

2019 ◽  
Vol 73 (1) ◽  
pp. 34-39
Author(s):  
Aldis Strēlnieks ◽  
Alberts Bērziņš ◽  
Māra Karakone ◽  
Irina Pupkeviča ◽  
Kristīne Jubele ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Direct Current ◽  
Antiarrhythmic Drugs ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Electrical Cardioversion ◽  
University Hospital ◽  
Recurrence Rates ◽  
Direct Current Cardioversion ◽  
Increased Risk

Abstract Patients with atrial fibrillation are faced with an increased risk of thromboembolic events, myocardial infarction, chronic heart failure and death. For some patients with atrial fibrillation, direct current cardioversion (DCCV) is a strategy that can be used to reacquire sinus rhythm. Our aim was to analyse the most commonly used medications after an electrical cardioversion, the reasons for not using them, the effects of pharmacotherapy on recurrence rates, and compare results with data from studies in 2014. The prospective study includes patients with electrocardiographically confirmed atrial fibrillation who underwent direct current cardioversion, hospitalised at Pauls Stradiņš Clinical University Hospital (Rīga, Latvia). The average age was 64.6 years. 50% of the patients were female. During the six-month study period, 14.3% patients were using amiodarone, 8.3% patients were on etacizine, 7.1% received propafenone, and 57.1% used beta blockers in monotherapy or in combination. Warfarin was used in 28.0% patients, direct oral anticoagulants (DOAC’s) in 29.9%, 21,4% of patients received aspirin and 16.7% did not use any antithrombotic therapy. Comparing the recurrence rate in patients using different antiarrhythmic drugs, amiodarone showed a statistically significant superiority compared to etacizine and propafenone (p = 0.02). The obtained data showed that over four years, the use of anticoagulants increased by 11.6%.

scholarly journals Laboratory bleeding predictors in elderly patients with atrial fibrillation taking direct oral anticoagulants

2020 ◽  
pp. 40-43
Author(s):  
M. A. Gabitova ◽  
P. M. Krupenin ◽  
A. A. Sokolova ◽  
D. A. Napalkov ◽  
V. V. Fomin
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Anticoagulant Therapy ◽  
Patient Monitoring ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Laboratory Methods ◽  
Increased Risk ◽  
Hemorrhagic Events ◽  
Clinically Significant

Atrial fibrillation (AF) is one of the most common arrhythmias in patients ≥75 years of age. The increased risk of thrombosis due to age and the large number of concomitant diseases makes it evident that anticoagulant therapy is necessary. However, the same factors increase the risk of hemorrhagic complications, which are among the most dangerous side effects of anticoagulant therapy. That is why it is very important to identify patients with the highest probability of bleeding, whether large or small clinically significant and minor. The purpose of our study was to study the prognostic value of laboratory methods of examination with regard to the development of hemorrhagic events in elderly patients with AF taking direct oral anticoagulants (DOAC). The study enrolled 102 patients ≥75 years of age with AF of non-valve etiology taking dabigatran, apixaban, rivaroxaban at full or reduced doses. Anticoagulants were administered by outpatient and inpatient physicians. Both previous experience with DOAC prior to inclusion in the trial (if DOAC was previously prescribed) and prospective patient monitoring after inclusion in the trial were analyzed. The minimum analyzed period of DOAC intake was 18 months. Patients who underwent (n = 19) and did not undergo (n = 83) hemorrhagic events (all events were considered small by ISTH criteria) did not differ in any of the laboratory indicators potentially considered as predictors of hemorrhagic events.

scholarly journals The Nephrological Aspects of the Use of Rivaroxaban and Other Direct Peroral Anticoagulants in Non-Valvular Atrial Fibrillation

Kardiologiia ◽  
2019 ◽  
Vol 59 (6) ◽  
pp. 60-69
Author(s):  
M. M. Batiushin
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Adverse Outcomes ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Increased Risk

Chronic kidney disease (CKD) is a powerful cardiovascular risk factor, its presence is accompanied by an increased risk of hospitalization for exacerbation of chronic heart failure (CHF), adverse outcomes in myocardial infarction, and cardiovascular mortality. Among the adverse events, an increased risk of atrial fibrillation (AF) should be noted. This article contains discussion of current approaches to the treatment of AF in patients with different stages of CKD, data on benefits of certain direct oral anticoagulants, as well as comparative characteristics of therapy with direct oral anticoagulants and warfarin. Pharmacokinetics and pharmacodynamics of direct oral anticoagulants, which determine the features of therapy in CKD, are also considered.

scholarly journals Safety of Using Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Chronic Kidney Disease

2019 ◽  
Vol 15 (4) ◽  
pp. 530-537 ◽  
Author(s):  
V. I. Petrov ◽  
O. V. Shatalova ◽  
A. S. Gerasimenko ◽  
V. S. Gorbatenko
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Renal Pathology ◽  
Rapid Progression ◽  
Thromboembolic Complications ◽  
Randomized Studies ◽  
Increased Risk

The purpose of this review is to examine the possibilities and prospects for the use of direct oral anticoagulants for the prevention of thromboembolic complications in patients with atrial fibrillation and chronic kidney disease. Chronic kidney disease is an independent risk factor for cardiovascular complications. Atrial fibrillation is associated with a higher risk of developing chronic kidney disease and more rapid progression of existing renal pathology. The presence of chronic kidney disease in atrial fibrillation on the one hand leads to an increased risk of thromboembolism, and on the other to an increased risk of bleeding when using anticoagulants. The standard for the prevention of thromboembolic complications in atrial fibrillation, including those with concomitant renal pathology, was considered warfarin for many years. However, modern studies have shown that the use of warfarin may enhance vascular calcification in patients with chronic kidney disease, which in turn may lead to an increased risk of ischemic strokes.Analyzing clinical recommendations, randomized studies, meta-analyzes and a systematic review on the use of anticoagulants in patients with atrial fibrillation and renal pathology, revealed the advantage of using direct oral anticoagulants over warfarin at stage 1-3 of chronic kidney disease. Data on the use of direct oral anticoagulants with a more pronounced renal dysfunction and in patients on dialysis is limited due to the lack of a sufficient number of large randomized studies. Due to the presence of renal clearance in all oral anticoagulants, their pharmacokinetics changes to some extent with a decrease in the glomerular filtration rate, which requires dose adjustment of drugs depending on creatinine clearance. Therefore, the use of anticoagulants for the prevention of thromboembolic complications during atrial fibrillation requires special attention in patients with chronic kidney disease.

The Impact of Body Weight and Renal Function on the Risk of Bleeding With Direct Oral Anticoagulants in Atrial Fibrillation

2021 ◽  
pp. 106002802199520
Author(s):  
Hannah Whittemore ◽  
Andrew K. Posen ◽  
Erika L. Hellenbart ◽  
Vicki Groo ◽  
Eric Wenzler ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Renal Function ◽  
Body Weight ◽  
Renal Dysfunction ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Events ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
The Impact

Background: Atrial fibrillation (AF) increases the risk of stroke and direct oral anticoagulants (DOACs) are first-line agents for prevention. Gaps in the literature cause reluctance in prescribing DOACs for patients with renal dysfunction and/or extremes in body weight. Objective: To evaluate the impact body weight and renal function have on major and clinically relevant nonmajor (CRNM) bleeding events and ischemic strokes in AF patients receiving a DOAC. Methods: This retrospective cohort study included adults with nonvalvular atrial fibrillation (NVAF) or atrial flutter (AFL) receiving a DOAC ≥12 months. The primary outcome was a composite of major and CRNM bleeding events. Secondary outcomes included ischemic stroke and risk factors for bleeding events. Results: Of the 233 patients analyzed, 25 patients experienced a bleeding event. Patients who bled weighed 10 kg less ( P = 0.043) than those who did not and had a higher HASBLED score ( P = 0.003). Multivariate logistic regression identified weight ( P = 0.048), serum creatinine (SCr; P = 0.027), and HASBLED score ( P = 0.024) as the significant predictors for experiencing a bleed. Three patients experienced a stroke. Conclusion and Relevance: This study demonstrates an association between higher baseline SCr, elevated HASBLED score, and lower weight, with an increased risk of bleeding in patients with NVAF or AFL receiving a DOAC. These findings add to prescribing considerations when initiating DOACs. Closer monitoring is advised for patients with significant renal dysfunction and/or low body weight, even with renal dose adjustments.

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