scholarly journals Influence of ABCB1 Gene Polymorphism on Rivaroxaban Blood Concentration and Hemorrhagic Events in Patients With Atrial Fibrillation

2021 ◽  
Vol 12 ◽  
Author(s):  
Yan Wang ◽  
Min Chen ◽  
Hui Chen ◽  
Fang Wang
Keyword(s):  
Atrial Fibrillation ◽  
Blood Concentration ◽  
Plasma Concentrations ◽  
Multiple Comparisons ◽  
Bleeding Events ◽  
Abcb1 Gene ◽  
Management Protocol ◽  
Significant Difference ◽  
Hemorrhagic Events ◽  
Trough Concentrations

Background and Objectives: Genetic data on the pharmacokinetics of rivaroxaban and identification of factors that affect its biotransformation, distribution, and excretion will allow for generation of algorithms for personalized use of this drug in patients with atrial fibrillation (AF). Here we tested the effects of ABCB1 (ATP-binding cassette subfamily B member 1) polymorphisms on the valley rivaroxaban blood concentration and on the frequency of hemorrhagic events in patients with AF and propose a personal anticoagulation therapy management protocol.Patients and Methods: This is a retrospective study. We enrolled Mongolian descent patients who met the criteria from May 2018 to August 2019 in Beijing and Fujian. Clinical data on gender, height, weight, liver and kidney functions, drug trough concentration, and drug dosage were collected; we recorded the bleeding events until 6 months after initiating the medication. ABCB1 single nucleotide polymorphisms including rs1128503, rs1045642, and rs4148738 were identified. After reaching the steady state of plasma concentration, the peripheral blood was collected to detect the trough rivaroxaban plasma concentrations before the next medication.Results: We included 155 patients in this study including 81 men and 74 women, with an average age of 71.98 ± 10.72 years. The distribution of ABCB1 genotypes conformed to the Hardy–Weinberg equilibrium. Multiple comparisons between wild (TT) and mutant (CT and CC) genotypes at the rs1045642 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, p = 0.586; TT vs. CC, p = 0.802; and CT vs. CC, p = 0.702). Multiple comparison between wild (TT) and mutant (CC) genotypes at the rs1128503 locus revealed a significant difference of rivaroxaban trough concentrations (TT vs. CC, p = 0.0421). But wild (TT) vs mutant (CT) genotypes and mutant CT vs mutant CC genotypes at the rs1128503 locus showed no significant differences of rivaroxaban trough concentrations (TT vs. CT, p = 0.0651; TT vs. CT, p = 0.6127). Multiple comparisons between wild (GG) and mutant (AG and AA) genotypes at the rs4148738 locus showed no significant differences of rivaroxaban trough concentrations (GG vs. AG, p = 0.341; GG vs. AA, p = 0.612; AG vs. AA, p = 0.649). There was no significant correlation between ABCB1 gene variation loci rs1045642, rs1128503, rs4148738 and bleeding events.Conclusion: rs1128503 locus variations are correlated with the serum concentration of rivaroxaban in patients of Mongolian descent. But no significant correlation between rs1128503 locus variations and bleeding events were obtained.

scholarly journals The Elevation of LIVER Enzymes in Patients with Atrial Fibrillation and COVID-19 Is a Marker of Bad Evolution and Mortality

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Juan Jose Cerezo Manchado ◽  
Pável E Olivera ◽  
María Dolores Lopez Abellan ◽  
Desiree Campoy Castaño ◽  
César A Velasquez ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Board Of Directors ◽  
Liver Enzymes ◽  
Predictor Variable ◽  
Bleeding Events ◽  
Advisory Committees ◽  
Significant Difference ◽  
Hemorrhagic Events ◽  
The Impact

Introduction: The COVID-19 pandemic reflects liver damage. A study carried out in China (Guan WJ et al. N Engl J Med. 2020) reported that in more than 21% of cases there was an elevation of liver enzymes (ELE), with only 2.1% of them having previous liver disease. ELE is frequent in anticoagulated patients and is associated with an increased cardiovascular risk and bleeding complications2,3. It is necessary to evaluate the impact of ELE in patients with atrial fibrillation (AF) and COVID-19 Methods: Multicenter, retrospective and observational study that consecutively included patients admitted with COVID-19 during the months of March and April 2020. The patients were followed were followed up until 30 days after discharge or death. termino en inglés ¿??Anticoagulation was chosen at the clinical discretion. The main variables investigated were the value of liver enzymes (AST, ALT, GGT) at admission, during the first week (peak value) and at hospital discharge. Patients who achieved a 3-fold higher level of ELE(> 120UI) were described as high-risk transaminasemia (HRT). The number of bleedings, thromboembolic events, as well as all-cause mortality were evaluated. Statistical analysis was performed with SPSS 21.0 (SPSS Inc., Chicago, IL). Results: A total of 235 patients were included. The mean age was 79 years [standard deviation (SD) 7.9. years]. The demographic characteristics of the patients with and without HRT are summarized in Table 1. The median follow-up was 59 days (SD 29 days). In AF patients, ELE values rose significantly on admission with respect to discharge p <0.05. No significant difference in the value of ELE was found between those who received LMWH versus ACODS. In patients with AF, there were 30 admissions to intensive care, these had higher ELE values at admission and at discharge, awith ALT at admission and ALT, AST and GGT at discharge being significant, p <0.05. They also presented 24 (10%) bleeding events, which had a significantly higher AST level in the first week (42-60UI). There were 45 (19.1%) patients who died during de follow-up, ELE values were significantly higher on admission. Finally, if we analyze the events in the 48 HRTpatients (21%) compared to the non-TAR 187 patients (79%), they had significantly more hemorrhagic events, and death from all causes, p <0.05, events was resume in Table 2. If we perform a logistic regresión for TAR as a predictor variable of bleddings events, TAR was a risk marker ,independly OR 3,6(1,39-9,33), table 3 Conclusion: In our cohort, AF patients who suffered events had a higher ELE than those who did not suffer significantly. Furthermore, the patients classified as HRT presented an increase in mortality, bleedings events compared to non-HRT (Table 2 and 3). No significant differences were observed in the elevation of the ELE according to the antithrombotic treatment, the patients treated with DOACs did not experience a significant increase in the ELE during the follow-up. Disclosures Olivera: Daiichi Sankyo:Consultancy, Speakers Bureau;BAYER:Consultancy;Boehringer Ingelheim:Consultancy, Speakers Bureau;Pfizer:Consultancy, Speakers Bureau.Campoy Castaño:Boehringer Ingelheim:Consultancy;Daiichi Sankyo:Speakers Bureau.Sierra:Astellas:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Abbvie:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Jazz Pharmaceuticals:Research Funding;Pfizer:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Daiichi Sankyo:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead-Kite:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

P1860Unfractionated heparin dose and complication rate in catheter ablation of atrial fibrillation, a comparison between uninterrupted therapy with phenprocoumon and direct oral anticoagulants

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
N Poci ◽  
D Gjermeni ◽  
V Kuehlkamp
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Events ◽  
Anticoagulation Management ◽  
Significant Difference ◽  
The Mean ◽  
Initial Bolus

Abstract Background Catheter ablation of atrial fibrillation is known for the combining risks of thromboembolism (TE) and major bleedings. This urges a better understanding and optimization of the intraprocedural anticoagulation management. Differences in unfractionated heparin (UFH) requirements and anticoagulation time (ACT) levels between patients on different uninterrupted oral anticoagulation (OAC) agents have been studied. However, the clinical relevance, in terms of periprocedural TE and bleeding events, of UFH administration according to ACT monitoring among patients on different OAC agents, needs to be addressed. Objective To evaluate how the ACT monitoring and differences in intraprocedural UFH requirements among different anticoagulant agents, may translate to clinical outcome, in terms of periprocedural incidence of thromboembolic and bleeding events. Methods We retrospectively studied 1571 cases who underwent catheter ablation for atrial fibrillation between January 2011 and May 2017. Cases were on an uninterrupted oral OAC therapy of Vitamin K Antagonists (VKA)(713), Rivaroxaban (RG)(385), Dabigatran (DG)(260), Apixaban (AG)(192) and Edoxaban (EG)(21). First ACT measurements after the initial bolus of UFH (1ehz748.0610U), mean ACT measurements, total UFH doses/kg (Body Weight)/min (duration of procedure) and incidence of major periprocedural events were compared among the above OAC groups. Results The mean ACT (sec) was significantly lower in the AG and greater in the VKA (313,7±47 vs 340,5±49, p<0,001). Significantly lower UFH doses (U/kg/min) were required to reach the target ACT in VKA compared to RG, DG, AG and EG (0,69±0,4 vs 1,41±0,76; 1,42±0,7; 1,63±0,8; 1,37±0,4 respectively, p<0,001) The proportion of patients who achieved a target ACT value within 30 minutes after the fixed first UFH Bolus of 10 000 U was significantly lower in DG and AG compared to VKA, EG and RG group (51,5% and 49% vs 53%, 71,4%, and 61,8% respectively p=0,005). The incidence of periprocedural TE events and bleedings showed no significant difference among OAC groups. However, the 22 patients with a periprocedural TE event had significantly lower UFH doses (U)/ Duration of catheter ablation (min) compared to the ones without periprocedural TE (62,71±44,5 vs 94,4±66,4, p=0,026), despite equivalent mean ACT values between these two groups. Patients with a periprocedural TE had also a significantly older Age (69,6±10 vs 64±10 p=0,01, higher CHADSVASC Score (3,64±1,76 vs 2,63±1,7 p=0,006), longer duration of procedure (188,9±79,1 vs 144,9±57 p=0,0001) and higher pre-Ablation INR values (2,2±0,6 vs 1,7±0,6 p=0,002). Conclusions The average UFH doses required to reach the target ACT were lower in VKA than in NOAC- groups. The incidence of periprocedural TE events and bleedings was equivalent among OAC groups. Patients with TE showed a lower UFH requirement compared to no-TE group, with both groups having mean ACT ≥300 sec.

P4742Evaluation of the HAS-BLED, ATRIA and ORBIT bleeding risk scores in newly diagnosed non-valvular atrial fibrillation

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
L Bergamaschi ◽  
A Stefanizzi ◽  
M Coriano ◽  
P Paolisso ◽  
I Magnani ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Independent Predictor ◽  
Bleeding Risk ◽  
Risk Scores ◽  
Newly Diagnosed ◽  
Bleeding Events ◽  
Hemorrhagic Events ◽  
Major Bleeding Events

Abstract Background Several risk scores have been proposed to assess the bleeding risk in patients with Atrial Fibrillation. Purpose To compare the efficacy of HAS-BLED, ATRIA and ORBIT scores to predict major bleedings in newly diagnosed non-valvular AF (NV-AF) treated with vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Methods We analyzed all consecutive patients with AF at our outpatient clinic from January to December 2017. Only those with new diagnosed NV-AF starting new anticoagulant therapy were enrolled. Major hemorrhagic events were defined according to the ISTH definition in non-surgical patients. Results Out of the 820 patients admitted with AF, 305 were newly diagnosed with NV-AF starting oral anticoagulation. Overall, 51.3% were male with a mean age of 72.6±13.7 years. Thirty-six patients (11.8%) started VKAs whereas 269 (88.2%) patients were treated with NOACs. The median follow-up time was 10.4±3.4 months. During follow-up, 123 (32.2%) bleeding events were recorded, 21 (17,1%) in the VKA group and 102 (82,9%) in the NOAC group. Eleven (2.9%) major bleeding events occurred: 5 (45.5%) in the VKA group and 6 (54.5%) in the NOAC group. Overall, patients with major hemorrhagic events showed a mean value of the scores significantly higher when compared to patients without such bleeding complications (HASBLED 3.4 vs 2.4 p=0.007; ATRIA 5.6 vs 2.4 p<0.001; ORBIT 3.6 vs 1.8 p<0,001). Conversely, when analyzing the VKA subgroup, only the ATRIA score was significantly higher in patients with major adverse events (7.4 vs 3.5 p<0.001; HAS-BLED: 4.4 vs 3.6 p=0.27; ORBIT 4.4 vs 2.9 p=0.13). An ATRIA score ≥4 identified patients at high risk of bleeding (29.4% vs. 0% events. respectively, p=0.04). In the NOAC group, patients with major bleeding events had higher mean values of ATRIA (4.0 vs 2.3 p=0.02) and ORBIT (2.8 vs 1.6 p=0,04) but not the HAS-BLED (2.5 vs 2.3 p=0.57) scores. Similarly, patients on NOACs with an ATRIA score ≥4 had higher rates of major bleedings (8.1% vs. 1.6% p=0,02). Comparing the single elements of the ATRIA score, only glomerular filtration rate <30 ml/min/1.73 mq was associated with major bleedings in the VKA group (p<0.001) whereas, in the NOAC group, anemia was strongly associated with bleeding events (p=0,02). In fact, multivariate analysis in the NOAC group showed that hemoglobin level at admission was an independent predictor for major bleeding events (OR 0.41, 95% CI 0.23–0.75, P=0.003). Conversely, in the VKA group, baseline creatinine level was an independent predictor for these events (OR 12.76, 95% CI 1.6–101.7, P=0.016). Conclusions The ATRIA score showed the best efficacy in predicting major bleeding events. Hemoglobin and creatinine levels at admission were independent predictors for major hemorrhagic events in the NOAC and in the VKA groups, respectively. The latter finding might be helpful in stratifying the hemorrhagic risk at the beginning of treatment.

scholarly journals Safety of dabigatran in patients with atrial fibrillation and chronic kidney disease: pharmacokinetic and pharmacogenetic aspects

2020 ◽  
pp. 65-73
Author(s):  
A. I. Skripka ◽  
P. O. Bochkov ◽  
K. A. Akmalova ◽  
R. V. Shevchenko ◽  
P. M. Krupenin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Nucleotide Polymorphisms ◽  
Bleeding Events ◽  
Day Range ◽  
High Interindividual Variability ◽  
Trough Concentrations ◽  
Moderate Chronic Kidney Disease ◽  
D Values

Background: despite well-studied safety profile of dabigatran its interactions with genetic polymorphism parameters are poorly understood, especially in patients with moderate chronic kidney disease (CKD). This study was aimed to evaluate relationships between CES1 and ABCB1 polymorphism, dabigatran trough plasma concentration (DTPC) and bleeding events in patients with AF and CKD.Methods: patients with atrial fibrillation (AF) and stage 3 CKD treated with dabigatran 110mg or 150 mg have been included in the study. Real-time PCR was used to evaluate single nucleotide polymorphisms (SNPs) of the ABCB1 gene (rs1045642, rs4148738) and CES1 gene (rs2244613). A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index.Results: a total of 60 patients, aged 51–89 years (median age 76 years) were evaluated. Compared with patients given 150 mg twice a day, those given 110 mg twice a day were older (79 vs 67.5, p < 0.0001) and had lower creatinine clearance (CrCl) (50.5 vs 60.5 mL/min/1.73 m2, p = 0.015). We found C/D values to have high interindividual variability (mean 365.9 ± 290.4 μg/ml: mg/day, range 23.64-1452.73). Individuals with CKD 3B had higher concentration of dabigatran compared with those with 3A stage (488.7 ± 232.3 vs 332 ± 297.8 μg/ml : mg/day, p = 0.02). Consequently, there also was negative correlation of C/D with CrCl (r = -0.4, p = 0.0015). Evaluated SNPs (rs1045642, rs4148738, and rs2244613) did not affect C/D values (H test p > 0.05).Conclusions: C/D values were significantly higher in patients with CKD 3B stage and those treated with dabigatran 110 mg. There was no influence of aforementioned SNPs on dabigatran trough concentrations and clinical outcomes.

scholarly journals Atrial Fibrillation Ablation without Interruption of Anticoagulation

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Pasquale Santangeli ◽  
Luigi Di Biase ◽  
Javier E. Sanchez ◽  
Rodney Horton ◽  
Andrea Natale
Keyword(s):  
Atrial Fibrillation ◽  
Radiofrequency Catheter Ablation ◽  
Minor Bleeding ◽  
Thromboembolic Events ◽  
Increased Risk ◽  
Significant Difference ◽  
Hemorrhagic Events ◽  
Ischemic Attack ◽  
Periprocedural Stroke ◽  
Pulmonary Vein Antrum Isolation

Atrial fibrillation (AF) can be cured by pulmonary vein antrum isolation (PVAI) in a substantial proportion of patients. The high efficacy of PVAI is partially undermined by a small but concrete periprocedural risk of complications, such as thromboembolic events and bleeding. A correct management of anticoagulation is essential to prevent such complications. Performing PVAI without interruption of oral anticoagulation has been demonstrated feasible by our group in previous studies. Recently, we reported that continuation of therapeutic warfarin during radiofrequency catheter ablation consistently reduces the risk of periprocedural stroke/transient ischemic attack without increasing the risk of hemorrhagic events. Of note, interrupting warfarin anticoagulation may actually increase the risk of stroke even when bridged with heparin. The latter strategy is also associated with an increased risk of minor bleeding. With regard to major bleeding, we found no significant difference between patients with a therapeutic INR and those who were bridged with heparin. Therefore, continuation of therapeutic warfarin during ablation of AF appears to be the best anticoagulation strategy. In this paper we summarize our experience with AF ablation without interruption of anticoagulation.

scholarly journals P1307HEMORRHAGIC VERSUS ISCHEMIC RISK IN PATIENTS WITH ATRIAL FIBRILLATION ON HEMODIALYSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Mariana Sousa ◽  
Pedro Bravo ◽  
Cristina Santos ◽  
Aura Ramos
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Risk Factor ◽  
Oral Anticoagulation ◽  
Thromboembolic Event ◽  
Previous Stroke ◽  
Significant Difference ◽  
Hemorrhagic Events ◽  
Ischaemic Attack ◽  
Ischemic Attack

Abstract Background and Aims Patients with renal replacement therapy and atrial fibrillation (AF) have a particularly high risk of both stroke and bleeding, but no high-quality evidence-based recommendations exist to properly manage these patients. Therefore, we aim to evaluate the ischaemic versus the haemorrhagic risk in a hemodialysis (HD) population. Method We selected patients that started hemodialysis in our hospital between 2011 and 2015. Only incident patients that were on regular hemodialysis treatment for more than 3 months were considered. Both patients that already had AF before HD, or developed AF during the follow-up, were included. At the time of AF diagnosis or beginning of HD, the risk factors were analyzed based on CHA2 DS2 -VASC and HAS-BLED scores. The outcomes were hemorrhagic events (only the events that needed hospitalization were taken into account), ischaemic events (i.e. that result from embolic arterial ischaemia) and death related to any of these events. Results From 302 incident patients on hemodialysis, 46 (15.23 %) were included. Mainly man (65%), with a mean age of 75 ± 10 years old. Most of the patients (63%) already had AF when they started hemodialysis. There was no significant difference between the incidence of ischaemic and haemorrhagic events (p=0.219). Three patients died of an ischemic event and two of haemorrhagic shock.Twenty one patients (45.6%) started oral anticoagulation. No difference was found between the proportion of haemorrhagic events between patients with oral anticoagulation and patients with no anticoagulation (p=0.157). Similarly, oral anticoagulation was not associated with any effect on the incidence of ischaemic events (p=0.366). The results after adjustment for the risk factors included in the HAS-BLED and CHA2 DS2-VASC scores were the same. Previous stroke, transient ischaemic attack or thromboembolic event significantly increased the risk of an ischaemic event, when adjusted to oral anticoagulation, age, diabetes, vascular disease and hypertension (OR 6.78, C.I 95% 1.236-37.278, p=0.028). This risk factor was not associated with an increase of haemorrhagic events. No other risk factor included in the scores was associated with any significant effect in the outcomes. Conclusion As we know, AF increases the risk of ischaemic events in general population. However, in hemodialysis patients, we didn’t observe any difference between the incidence of ischaemic and haemorrhagic events. Therefore, the benefit of oral anticoagulation in such patients remains questionable. It is worth noting that patients with previous stroke, transient ischemic attack or thromboembolic event seem to have higher risk of new ischaemic events. In these patients, there may be some advantage in oral anticoagulation. Since this is a single center, retrospective, observational study, these results should be interpreted with caution.

scholarly journals Laboratory Assessment of the Anticoagulant Activity of Apixaban in Patients With Nonvalvular Atrial Fibrillation

2018 ◽  
Vol 24 (9_suppl) ◽  
pp. 194S-201S ◽  
Author(s):  
Elias Kyriakou ◽  
Konstantinos Katogiannis ◽  
Ignatios Ikonomidis ◽  
George Giallouros ◽  
Georgios K. Nikolopoulos ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Thrombin Generation ◽  
Anticoagulant Activity ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Plasma Concentrations ◽  
Nonvalvular Atrial Fibrillation ◽  
Laboratory Assessment ◽  
Thrombin Generation Assay ◽  
Significant Difference

Our aim is to determine the most appropriate laboratory tests, besides anti-factor Xa (anti-FXa) chromogenic assays, to estimate the degree of anticoagulation with apixaban and compare it with that of rivaroxaban in real-world patients. Twenty patients with nonvalvular atrial fibrillation treated with apixaban 5 mg twice daily and 20 patients on rivaroxaban 20 mg once daily were studied. Conventional coagulation tests, thrombin generation assay (TGA), and thromboelastometry (nonactivated TEM [NATEM] assay) were performed in the 40 patients and 20 controls. The anti-FXa chromogenic assays were used to measure apixaban and rivaroxaban plasma levels. The NATEM measurements showed no significant difference between the 2 groups of patients. Concerning TGA, endogenous thrombin potential (ETP) was significantly decreased in patients on rivaroxaban as compared to those treated with apixaban ( P < .003). A statistically significant, strong inverse correlation between apixaban plasma concentrations and ETP ( P < .001) was observed. Apixaban significantly reduces ETP compared to controls, but to a lesser extent than rivaroxaban. Thrombin generation assay might provide additional information on apixaban exposure, which is required in order to individualize treatment especially for patients with a high bleeding risk. Our findings have to be further investigated in studies with larger sample sizes, in the entire range of apixaban exposure, with other direct oral anticoagulants, and in relation to clinical outcomes.

scholarly journals Clinical Safety Outcomes in Patients With Nonvalvular Atrial Fibrillation on Rivaroxaban and Diltiazem

2018 ◽  
Vol 53 (1) ◽  
pp. 21-27 ◽  
Author(s):  
Jenna W. Bartlett ◽  
Elizabeth Renner ◽  
Erin Mouland ◽  
Geoffrey D. Barnes ◽  
Liane Kuo ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Bleeding Event ◽  
Cytochrome P450 Enzyme ◽  
Bleeding Events ◽  
Nonvalvular Atrial Fibrillation ◽  
Retrospective Case ◽  
Clinical Safety ◽  
Glycoprotein P ◽  
Significant Difference ◽  
P450 Enzyme

Background: It is unknown whether diltiazem, a moderate cytochrome P450 enzyme (CYP3A4) and P-glycoprotein (P-gp) inhibitor, increases the incidence of bleeding events in combination with rivaroxaban, a CYP3A4 and P-gp substrate. Objective: To assess major and clinically relevant nonmajor (CRNM) bleeding outcomes in patients with nonvalvular atrial fibrillation (NVAF) on rivaroxaban with concomitant diltiazem in a real-world setting. Methods: This retrospective case-cohort study included adult patients with NVAF prescribed both rivaroxaban and diltiazem for at least 30 days. Patients were matched 1:1 by age and baseline creatinine clearance (CrCl) to control patients taking rivaroxaban alone. The primary outcome was the composite of major and CRNM bleeding. Additional outcomes included bleeding events resulting in discontinuation of rivaroxaban, time to first bleeding event, and type of first bleed. Results: A total of 143 cases and 143 controls were included. The mean age was 69 years and median baseline CrCl was 87 mL/min. Median follow-up time was 12.4 months for cases and 16.5 months for controls. There was no significant difference in proportion of patients experiencing a major and/or CRNM bleeding event between cases and controls: 23.1% versus 28.0%, respectively; 9 cases and 8 controls permanently discontinued rivaroxaban because of bleeding. Gastrointestinal/rectal bleeding and hematuria were the most frequently reported bleeding events in both groups. Conclusion and Relevance: This is the first study to assess major and CRNM bleeding outcomes in patients with NVAF on rivaroxaban and diltiazem. Diltiazem use was not associated with an increased rate of bleeding events.

scholarly journals Interindividual Variability of Apixaban Plasma Concentrations: Influence of Clinical and Genetic Factors in a Real-Life Cohort of Atrial Fibrillation Patients

Genes ◽  
2020 ◽  
Vol 11 (4) ◽  
pp. 438
Author(s):  
Adela-Nicoleta Roşian ◽  
Ştefan Horia Roşian ◽  
Bela Kiss ◽  
Maria Georgia Ştefan ◽  
Adrian Pavel Trifa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Plasma Level ◽  
Peak Plasma ◽  
Plasma Concentrations ◽  
Real Life ◽  
Pharmacokinetic Parameters ◽  
Liquid Chromatography Tandem Mass ◽  
Trough Concentrations ◽  
Abcb1 Genotype

(1) Background: Prescribing apixaban for stroke prevention has significantly increased in patients with non-valvular atrial fibrillation (NVAF). The ABCB1 genotype can influence apixaban absorption and bioavailability. The aim of the present study was to assess the factors that influence apixaban’s plasma level and to establish if a certain relationship has clinical relevance. (2) Methods: Fifty-three NVAF patients were treated with 5 mg apixaban twice/day (70.0 years, range: 65–77, 60.4% men). Trough and peak plasma concentrations of apixaban were determined by liquid chromatography-tandem mass-spectrometry (LC-MS/MS), and ABCB1 genotyping was performed. (3) Results: Apixaban plasma concentrations varied considerably. They were higher in women than in men (311.2 ng/dL vs. 252.2 ng/dL; p = 0.05) and were lower in patients with heart failure (149.4 ng/dL vs. 304.5 ng/dL; p < 0.01). Creatinine clearance was inversely correlated with the apixaban plasma level (Spearman correlation: r = −0.365; p = 0.007 for trough concentrations). No statistically significant differences between the genotypic groups of ABCB1 rs1045642 and ABCB1 rs4148738 were found in the trough or peak apixaban plasma concentrations. (4) Conclusions: Pharmacokinetic parameters are influenced by several clinical factors of which renal function is the major determinant. Plasma concentrations measured in women had higher values than those measured in men, and heart failure was associated with decreased plasma levels of apixaban.

scholarly journals Bleeding Complications in Atrial Fibrillation Patients on Anticoagulant Therapy

2019 ◽  
Vol 70 (5) ◽  
pp. 1582-1585 ◽  
Author(s):  
Ionela Silivastru (Cozlea) ◽  
Gabriela Keresztesi ◽  
Arthur Atilla Keresztesi ◽  
Daniel Laurentiu Cozlea ◽  
Carmen Caldararu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Gastrointestinal Bleeding ◽  
Vitamin K ◽  
Oral Anticoagulant ◽  
Bleeding Event ◽  
Bleeding Complications ◽  
Anticoagulant Treatment ◽  
Bleeding Events ◽  
Oral Anticoagulant Treatment ◽  
Significant Difference

The risk of bleeding in atrial fibrillation patients on direct oral anticoagulant treatment increases with age; particularly dabigatran is associated with a higher risk of gastrointestinal bleeding in elderly patients, low body mass ([48 kg) and women due to the induced dyspepsia. We aimed to evaluate the safety of direct oral anticoagulants (DOAC) dabigatran, rivaroxaban and apixaban by comparing each agent with a widely used vitamin K antagonist (VKA)-acenocoumarol in terms of bleeding event rates. A retrospective study regarding bleeding events in atrial fibrillation patients treated with oral anticoagulation (OAC) was performed. Haematuria, epistaxis and haemoptysis were considered minor events and intracranial bleeding, gastrointestinal bleeding (superior or inferior), blood transfusion after haemorrhagic events linked to OAC treatment were considered to be major events. A number of 219 atrial fibrillation patients were included using electronic medical records: 118 patients treated with DOAC s (82 using dabigatran, 28 on rivaroxaban regimen and 8 cases treated with apixaban) and 101 cases had vitamin K antagonists treatment (acenocumarol). A total of 75 bleeding events were encountered (70 minor and 5 major). A higher number of events were encountered in patients treated with DOAC s, but with no statistically significant difference compared to acenocumarol. The associated risk factors did not play a decisive role in bleeding events in the two treatment groups. No statistical significant difference was noted between the occurrence of haemorrhagic events and the class of oral anticoagulant treatment used (DOAC vs. VKA).

Sign in / Sign up

Export Citation Format

Share Document