scholarly journals Possibilities of Using Rivaroxaban in Elderly Patients with Atrial Fibrillation: Data from Randomized Studies and Real Clinical Practice

2018 ◽  
Vol 14 (4) ◽  
pp. 575-582
Author(s):  
N. M. Vorobyeva ◽  
O. N. Kacheva
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Elderly Patients ◽  
Major Bleeding ◽  
Age Groups ◽  
Minor Bleeding ◽  
Systemic Embolism ◽  
Risk Of Death ◽  
Coronary Syndrome ◽  
Real Clinical Practice

The possibility of rivaroxaban using in elderly patients with non-valvular atrial fibrillation is discussed in the review. The results of ROCKET-AF randomized trial, including subgroup analysis in patients older than 75 years, are presented. The problem of unreasonable prescription of low doses of anticoagulants in real clinical practice and questions of adherence of patients to anticoagulant therapy are discussed. The results of two recent studies of actual clinical practice performed in patients over the age of 80 and 85 years, respectively, are presented as well as favorable profile of the efficacy and safety of rivaroxaban in these age groups. Rivaroxaban reduced the risk of stroke/systemic embolism by 38% and ischemic stroke by 41% with a comparable risk of major bleeding in patients older than 80 years. In another study, in patients older than 85 years in the rivaroxaban group, a 11% reduction in the risk of death from all causes, a reduction in the risk of major bleeding by 10% and an acute coronary syndrome by 14%, with similar risk of stroke/systemic embolism, clinically significant minor bleeding and a combined endpoint (stroke/systemic embolism, large bleeding, death from all causes) have been found.

scholarly journals APPROACHES TO THE CHOICE OF ANTICOAGULANT THERAPY IN THE TREATMENT OF PATIENTS WITH COMBINATION OF ATRIAL FIBRILLATION WITH CORONARY HEART DISEASE OR PERIPHERAL ATHEROSCLEROSIS: POTENTIAL OF APIXABAN

2018 ◽  
Vol 14 (3) ◽  
pp. 441-450
Author(s):  
O. D. Ostroumova ◽  
A. I. Kochetkov ◽  
I. Yu. Orlova ◽  
E. A. Smolyarchuk ◽  
J. S. Pavlova
Keyword(s):  
Atrial Fibrillation ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Anticoagulant Therapy ◽  
Major Bleeding ◽  
Minor Bleeding ◽  
Low Doses ◽  
Systemic Embolism ◽  
Coronary Syndrome ◽  
Risk Of Bleeding

The choice of anticoagulant therapy in patients with atrial fibrillation (AF) and concomitant diseases – coronary heart disease (CHD), including acute coronary syndrome (ACS) in history, peripheral arterial disease (PAD), is discussed in the article. The overall mortality and incidence of myocardial infarction in patients with CHD and AF is higher than in patients with AF without CHD. Patients with AF and PAD compared to patients with AF without PAD have higher risks both stroke and systemic embolism. The prescription of triple antithrombotic therapy is necessary for patients with a combination of AF and CHD who underwent percutaneous coronary interventions (in ACS or elective surgery). The possibility of prescription and duration, the choice of specific drugs and their doses should be determined individually, based on the risks of ischemic events associated with stenting, the risk of ischemic stroke and bleeding. Use of new oral anticoagulants (NOAC) instead of vitamin K antagonists (eg, warfarin), low doses of NOAC, studied in trials and proven efficacy in the prevention of stroke/systemic embolism, the use of clopidogrel as a drug of choice from the P2Y12 inhibitor group, the use of low doses of acetylsalicylic acid (ASA), the routine administration of drugs from the proton pump inhibitor group is recommended to minimize the risk of bleeding. The data of subanalysis of the ARISTOTEL randomized clinical trial, indicating a high profile of efficacy and safety of apixaban in patients with AF, depending on the presence of CHD, PAD, concomitant use of ASA, are also presented in the article. The benefits of apixaban over warfarin for reducing the risk of stroke/systemic embolism, total mortality and the risk of bleeding in a subgroup of CHD patients are just as obvious as in the general population of the ARISTOTLE study, and in the subgroup of patients without CHD. Treatment with apixaban, both in the subgroup of patients taking ASA, and a subgroup of patients without ASA, is accompanied by a lower risk of strokes and systemic embolism and a lower incidence of major bleeding. The risk of stroke or systemic embolism was similar in patients with AF and PAD randomized to the apixaban group or to the warfarin group, as well as in patients with AF without PAD. Patients with AF and PAD who received apixaban or warfarin had a similar incidence of major bleeding or clinically significant minor bleeding.

scholarly journals Anticoagulation Challenges in Hematogeriatrics: Effectiveness and Safety of Direct Oral Anticoagulants Vs Vitamin k Antagonist in Elderly with Atrial Fibrillation

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1162-1162
Author(s):  
Desirée Campoy ◽  
Gonzalo Artaza ◽  
César A Velasquez ◽  
Tania Canals ◽  
Erik A Johansson ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Vitamin K ◽  
Major Bleeding ◽  
Frail Elderly ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Systemic Embolism ◽  
Bleeding Events

BACKGROUND Direct oral anticoagulants (DOAC) are increasingly used in patients with Non Valvular Atrial Fibrillation (NVAF) for stroke prevention. However, Follow-Up (FU) and dosing these agents in the elderly can be challenging due to different factors, such as chronic kidney disease, frailty, falls, multifactorial anemia and concomitant polypharmacy. These factors in elderly patients predisposes to both thromboembolic and bleeding events once atrial fibrillation occurs. Therefore, balancing risks and benefits of antithrombotic strategies in older populations is crucial. Despite recent increases in DOAC use in NVAF, there are still limited data regarding DOACs effectiveness and safety in frail elderly patients. AIM To assess the effectiveness and safety according to DOAC or Vitamin K Antagonist (VKA) in a cohort of elderly patients with NVAF. METHODS From April 2016 to April 2019, we consecutively included NVAF elderly patients (≥80 years-old) treated with DOAC or VKA in a prospective multicenter registry. Demographic, laboratory, frailty risk stratification and antithrombotic therapy data were collected. Patients had a minimum FU of 6 months. VKA patients had a standard FU through digital international normalized ratio (INR) control and the efficacy of therapy was determined by the time in therapeutic range (TTR) values from the preceding 6 months of treatment using Rosendaal's method. FU in DOAC patients was performed through structured and integral assessment following the Tromboc@t Working Group recommendations for management in patients receiving DOAC (Olivera et al, Med Clin 2018). Key practical management aspects are listed in the flow chart (Figure 1). Clinical Frailty Scale (CFS score) was assigned to each patient at the beginning and during the FU; patients were classified into three categories: non-frail (CFS 1-4), mild-to-moderately frail (CFS 5-6), and severely frail (CFS 7-9). RESULTS From a total of 1040 NVAF patients, 690 (63.5%) were treated with DOAC (61 dabigatran, 95 rivaroxaban, 254 edoxaban and 280 apixaban) and 350 with VKA. In the VKA group, the mean TTR was 52.8%. Demographic characteristics and CFS score are summarized in table 1. Kaplan-Meier analysis (median FU: 16.5 months) showed a significantly high incidence of stroke/systemic embolism among VKA patients vs DOAC patients (4.2 vs 0.5 events per 100 patient-years, p<0.001). Major bleeding in the DOAC group was significantly infrequent compared with VKA group (2.2 vs 8.9 events, p=0.001). In the DOAC group, 90% (n=20/22) of the major bleedings were gastrointestinal [16 rivaroxaban and 4 edoxaban]. However, in the VKA group 64% (n = 20/31) were gastrointestinal, 25.8% (n= 8/31) intracranial and 9.7% (n = 3/31) urogenital bleedings. We identified 365 very elderly patients (aged ≥ 90 years) of which 270 (39.1%) were DOAC patients and 95 (27.1%) VKA patients. In this subgroup of patients, after a multivariate regression analysis, the stroke/systemic embolism incidence was similar in both treatment groups regardless of the age, but major bleeding decreased significantly in DOAC group (adjusted HR 0.247, 95% CI 0.091-0.664). CONCLUSIONS Our data indicate that DOACs can be a good therapeutic option for stroke/systemic embolism prevention in frail elderly patients, showing low rates of stroke as well as bleeding events when a structured and integral FU is applied to anticoagulated patients. Further investigations are necessary to analyze the impact in the quality of life and net clinical benefit of anticoagulant therapy when a FU program is applied in elderly patients. Disclosures Sierra: Novartis: Honoraria, Research Funding, Speakers Bureau; Astellas: Honoraria; Pfizer: Honoraria; Daiichi-Sankyo: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Roche: Honoraria; Jazz Pharmaceuticals: Honoraria.

P4758Label adherence of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation: A nationwide study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H T Yu ◽  
P S Yang ◽  
E Jang ◽  
T H Kim ◽  
J S Uhm ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Clinical Outcomes ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Systemic Embolism ◽  
Increased Risk ◽  
All Cause Mortality

Abstract Background Dose adjustment of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in some patients with atrial fibrillation (AF), based on selected patient factors or concomitant medications. Purpose We assessed the frequency of label adherence of NOAC dosing among AF patients and the associations between off-label NOAC dosing and clinical outcomes in real-world clinical practice. Methods We evaluated 53,649 AF patients treated with a NOAC using Korean National Health Insurance Service database during the period from January 2013 to December 2016. NOAC doses were classified as either underdosed or overdosed, consistent with U.S. Food and Drug Administration labeling. Cox proportional hazards regression was performed to investigate the effectiveness and safety outcomes including stroke or systemic embolism, major bleeding, and all-cause mortality. Results Overall, 16,757 NOAC-treated patients (31.2%) were underdosed, 4,492 were overdosed (8.4%), and 32,400 (60.4%) were dosed appropriately according to drug labeling. Compared with patients with label adherence, those who were underdosed or overdosed were older (71±8 and 75±7 years of age vs. 70±9 years of age, respectively; p<0.001), more likely female (39% and 53% vs. 38%, respectively; p<0.001), and had higher CHA2DS2-VASc scores (4.6±1.7 and 5.3±1.7 vs. 4.5±1.8, respectively; p<0.001). NOAC overdosing was associated with increased risk for stroke or systemic embolism (5.76 vs. 4.03 events/100 patient-years, p<0.001), major bleeding (4.77 vs. 2.94 events/100 patient-years, p<0.001), and all-cause mortality (5.43 vs. 3.05 events/100 patient-years, p<0.001) compared with label-adherent use. Figure 1 Conclusion In routine clinical practice, a significant proportion (almost 2 in 5) of AF patients received NOAC doses inconsistent with drug labeling. NOAC overdosing is associated with increased risk for stroke or systemic embolism, major bleeding, and all-cause mortality in Asian patient with AF.

scholarly journals Effectiveness and safety of oral anticoagulants in elderly patients with atrial fibrillation

Heart ◽  
2021 ◽  
pp. heartjnl-2020-318753
Author(s):  
Ole-Christian Walter Rutherford ◽  
Christian Jonasson ◽  
Waleed Ghanima ◽  
Fabian Söderdahl ◽  
Sigrun Halvorsen
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Major Bleeding ◽  
Standard Dose ◽  
Oral Anticoagulants ◽  
Vitamin K Antagonist ◽  
Sensitivity Analyses ◽  
World Population ◽  
Systemic Embolism ◽  
Reduced Dose

ObjectivesTo assess the risk of stroke/systemic embolism (SE) and major bleeding associated with the use of oral anticoagulants in elderly patients with atrial fibrillation (AF) in a real-world population.MethodsWe identified all anticoagulant-naive initiators of warfarin, dabigatran, rivaroxaban and apixaban for the indication AF in Norway between January 2013 and December 2017. Multivariate competing risk regression was used to calculate subhazard ratios (SHRs) describing associations between non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin for risk of stroke/SE and major bleeding.ResultsAmong 30 401 patients ≥75 years identified (median age 82 years, 53% women, mean CHA2DS2-VaSc score 4.5), 3857 initiated dabigatran, 6108 rivaroxaban, 13 786 apixaban and 6650 warfarin. Reduced dose was initiated in 11 559 (49%) of the NOAC-treated patients. For stroke, the SHRs for standard dose NOAC against warfarin were 0.80 (95% CI 0.57 to 1.13) for dabigatran; 1.07 (95% CI 0.89 to 1.30) for rivaroxaban and 0.95 (95% CI 0.78 to 1.15) for apixaban. For major bleeding, the SHRs against warfarin were 0.75 (95% CI 0.52 to 1.08) for dabigatran; 0.96 (95% CI 0.78 to 1.16) for rivaroxaban and 0.74 (95% CI 0.60 to 0.91) for apixaban. Comparing reduced doses of NOACs with warfarin yielded similar results. Sensitivity analyses were in accordance with the main results.ConclusionIn this nationwide cohort study of patients ≥75 years initiating oral anticoagulation for AF, standard and reduced dose NOACs were associated with similar risks of stroke/SE as warfarin and lower or similar risks of bleeding. The NOACs seem to be a safe option also in elderly patients.

scholarly journals What is Standard Dose of Rivaroxaban in Elderly Asian Patients with Atrial Fibrillation: 20ms versus. 15mg?

2021 ◽  
Vol 27 ◽  
pp. 107602962110611
Author(s):  
Sung Soo Kim ◽  
Ki Hong Lee ◽  
Nam Sik Yoon ◽  
Hyung Wook Park ◽  
Jeong Gwan Cho
Keyword(s):  
Atrial Fibrillation ◽  
Elderly Patients ◽  
Dose Reduction ◽  
Major Bleeding ◽  
Standard Dose ◽  
Comparable Efficacy ◽  
Systemic Embolism ◽  
Off Label ◽  
Korean Patients ◽  
Asian Patients

Although there is no age criterion for rivaroxaban dose reduction, elderly patients with atrial fibrillation (AF) are often prescribed an off-label reduced dose. We aimed to evaluate whether age is a necessary criterion for rivaroxaban dose reduction in Korean patients with AF. Among 2208 patients who prescribed warfarin or rivaroxaban, 552 patients over 75 years without renal dysfunction (creatinine clearance >50 mL/min) were compared based on propensity score matching. The rivaroxaban group was further divided into a 20 mg (R20; on-label) and a 15 mg (R15; off-label). Primary net clinical benefit (NCB) was defined as the composite of stroke, systemic embolism, major bleeding, and all-cause mortality. Secondary NCB was defined as the composite of stroke, systemic embolism, and major bleeding. Patients were followed for 1 year, or until the first outcome occurrence. Both rivaroxaban groups had comparable efficacy compared with warfarin. However, both R20 (0.9% vs 7.4%, p = .014) and R15 (2.3% vs 7.4%, p = .018) had a significant reduction in major bleeding. There were no differences in efficacy or safety outcomes between R20 and R15. R20 had significantly reduced primary (hazard ratio [HR] 0.33, 95% confidence interval [CI]: 0.12–0.93) and secondary (HR 0.31, 95% CI: 0.10–0.93) NCBs compared with warfarin. However, primary and secondary NCBs were not reduced in R15. In real-world practice with elderly patients with AF, off-label rivaroxaban dose reduction to 15 mg conferred no benefits. Therefore, guideline-adherent rivaroxaban 20 mg is favorable in elderly Korean patients with AF.

scholarly journals The risk of stroke/systemic embolism and major bleeding in Asian patients with non-valvular atrial fibrillation treated with non-vitamin K oral anticoagulants compared to warfarin: Results from a real-world data analysis

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242922
Author(s):  
Oh Young Bang ◽  
Young Keun On ◽  
Myung-Yong Lee ◽  
Sung-Won Jang ◽  
Seongwook Han ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Vitamin K ◽  
Major Bleeding ◽  
Oral Anticoagulants ◽  
Systemic Embolism ◽  
Real World Data ◽  
Level Of Evidence ◽  
Warfarin Group ◽  
Asian Patients

Background Although randomized trials provide a high level of evidence regarding the efficacy of non-vitamin K oral anticoagulants (NOACs), the results of such trials may differ from those observed in day-to-day clinical practice. Aims To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) between NOAC and warfarin in clinical practice. Methods Patients with non-valvular atrial fibrillation (NVAF) who started warfarin/NOACs between January 2015 and November 2016 were retrospectively identified from Korea’s nationwide health insurance claims database. Using inpatient diagnosis and imaging records, the Cox models with inverse probability of treatment weighting using propensity scores were used to estimate hazard ratios (HRs) for NOACs relative to warfarin. Results Of the 48,389 patients, 10,548, 11,414, 17,779 and 8,648 were administered apixaban, dabigatran, rivaroxaban and warfarin, respectively. Many patients had suffered prior strokes (36.7%, 37.7%, 31.4%, and 32.2% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), exhibited high CHA2DS2-VASc (4.8, 4.6, 4.6, and 4.1 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) and HAS-BLED (3.7, 3.6, 3.6, and 3.3 in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively) scores, had received antiplatelet therapy (75.4%, 75.7%, 76.8%, and 70.1% in apixaban, dabigatran, rivaroxaban, and warfarin group, respectively), or were administered reduced doses of NOACs (49.8%, 52.9%, and 42.8% in apixaban, dabigatran, and rivaroxaban group, respectively). Apixaban, dabigatran and rivaroxaban showed a significantly lower S/SE risk [HR, 95% confidence intervals (CI): 0.62, 0.54–0.71; 0.60, 0.53–0.69; and 0.71, 0.56–0.88, respectively] than warfarin. Apixaban and dabigatran (HR, 95% CI: 0.58, 0.51–0.66 and 0.75, 0.60–0.95, respectively), but not rivaroxaban (HR, 95% CI: 0.84, 0.69–1.04), showed a significantly lower MB risk than warfarin. Conclusions Among Asian patients who were associated with higher bleeding risk, low adherence, and receiving reduced NOAC dose than that provided in randomised controlled trials, all NOACs were associated with a significantly lower S/SE risk and apixaban and dabigatran with a significantly lower MB risk than warfarin.

scholarly journals Antithrombotic Therapy in Elderly Patients with Atrial Fibrillation: The State of the Problem in the Real Clinical Practice of a Family Medicine Doctor

2021 ◽  
Vol 6 (2) ◽  
pp. 63-69
Author(s):  
Bazira Kanat кyzy ◽  
N. K. Kinderbaeva ◽  
S. O. Turdaliyev ◽  
Zh. A. Mahmudova ◽  
U. K. Kundashev ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Family Medicine ◽  
Anticoagulant Therapy ◽  
Antithrombotic Therapy ◽  
Age Groups ◽  
Target Range ◽  
Specialized Team ◽  
Real Clinical Practice

Introduction. The research aimed at studying the efficacy and safety of anticoagulant therapy in patients with atrial fibrillation (AF), especially in older age groups, is now increasingly relevant.The aim of the study is to analyze the situation with prescribing anticoagulant therapy in elderly and senile persons with atrial fibrillation in real clinical practice and to demonstrate the possibility of improving the quality of observation and management of a group of patients as part of the work of a specialized team.Materials and methods. A total of 2,770 medical records of outpatient patients with atrial fibrillation were studied for the period from 2017 to 2019. Of this number, 320 patients with AF of nonvalvular etiology were selected, the average age of which was 70.3 ± 8.15 years. There were 270 women and 50 men. An observational prospective study in 45 elderly and senile patients with AF of non-valvular etiology was carried out by a team of specialized doctors for 12 months.Results. Of the 301 patients, anticoagulant therapy was prescribed to 166 (55.1 %), of which only 17 (10.2 %) people received proper anticoagulant therapy. The excessive activity was observed in 114 (37.9 %) patients, who underwent antiplatelet therapy with aspirin, and 21 (7.0 %) patients remained without any treatment with anticoagulants nor antiplatelet agents. Although, in the case of both, prescribing aspirin and not prescribing, anticoagulants have been indicated. In the prospective part of the study (for 12 months), all 45 patients continued to take anticoagulants and were systematically monitored. The INR in the target range over 60 % of the time was achieved in 37 % of patients receiving warfarin therapy.Conclusion. In the actual clinical practice of Kyrgyzstan family medicine centers, older patients with atrial fibrillation receive inadequate antithrombotic therapy. The main drug of choice for specialists remains warfarin, a therapy that can be recognized as adequate only in a small number (16 %) of patients. The ability to improve the quality of surveillance and management of a group of patients with AF and high adherence to treatment was demonstrated by the work of a specialized team of doctors. 

Abstract 484: Real World Experience with the Use of Dabigatran

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Archana Rajdev ◽  
Jacqueline Bradley ◽  
Eric Santos ◽  
Oanal Penciu ◽  
Jonathan Alexander
Keyword(s):  
Atrial Fibrillation ◽  
Drug Interactions ◽  
Major Bleeding ◽  
Community Setting ◽  
Minor Bleeding ◽  
New Era ◽  
Coronary Syndrome ◽  
History Of ◽  
Study Population ◽  
Accompanying Symptoms

Background The RE-LY trial in 2009 ushered in a new era in anticoagulation options for stroke prevention in atrial fibrillation.We sought to determine the safety, efficacy, and tolerability of dabigatran in a community setting. Methods We retrospectively reviewed demographics, bleeding rates, stroke rates, and reasons for discontinuation in patients on dabigatran for non-valvular atrial fibrillation. Results Of the 263 patients, mean age was 73.8 years (32 to 96) and 41.06% were female. The 150 mg BID dose was used in 93.54% of patients and 75 mg BID in 6.46%. Major bleeding was noted in 4 (1.52%), minor bleeding in 25 (9.5%), and rate of discontinuation was 22.3%. Patients who experienced major bleeding were more likely to be older, male, have higher HAS-BLED scores, and a history of gastrointestinal bleeds. All these patients were managed conservatively with no mortality.Of note, three of the four patients with major bleeds were on amiodarone in addition to dabigatran 150 mg BID.Two presented with transient ischemic attacks and had elevated PTTs suggesting compliance with dabigatran. Four patients who were admitted to the hospital with pneumonia, atrial fibrillation, and COPD exacerbation had elevated troponins without accompanying symptoms of acute coronary syndrome. In patients maintained on the 75 mg BID dose, minor bleeding was noted in two, who were also on dronedarone. No strokes or intracranial bleeds were noted in patients on either dose of dabigatran Conclusions This retrospective analysis demonstrates safety and efficacy of dabigatran as an oral anticoagulant in patients with non-valvular atrial fibrillation over a two-year follow-up while describing the factors associated with increased bleeding risk.It is the first study to describe experience with use of 75 mg of dabigatran. Drug interactions are a common and avoidable reason for dabigatran-associated bleeding and were noted with both amiodarone and dronedarone in our study. There was no increased incidence of myocardial infarction noted. In our study population, dabigatran is safe, effective, and convenient when there is careful patient selection with consideration of renal function and possible drug-drug interactions

scholarly journals Apixaban-Calibrated Anti-FXa Activity in Relation to Outcome Events and Clinical Characteristics in Patients with Atrial Fibrillation: Results from the AVERROES Trial

TH Open ◽  
2017 ◽  
Vol 01 (02) ◽  
pp. e139-e145 ◽  
Author(s):  
Vinai Bhagirath ◽  
John Eikelboom ◽  
Jack Hirsh ◽  
Michiel Coppens ◽  
Jeffrey Ginsberg ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Clinical Characteristics ◽  
Factor Xa ◽  
Entire Group ◽  
Minor Bleeding ◽  
Systemic Embolism ◽  
Nonvalvular Atrial Fibrillation ◽  
Clinical Trial Registration

Background In patients with nonvalvular atrial fibrillation (AF), apixaban is given in doses of 5 or 2.5 mg twice daily, according to clinical characteristics. The usual on-treatment range of apixaban drug levels, as determined by apixaban-calibrated anti-factor Xa (anti-Xa) activity, has previously been measured in small cohorts; however, the association between anti-Xa activity and clinical outcomes and the predictors of variability in anti-Xa activity have not been well studied in the AF population. Methods and Results Anti-Xa activity was measured before taking the morning dose, 3 months after enrollment in the AVERROES study using a calibrated anti-Xa assay (Rotachrom). Patients with two of the following criteria—age >80; weight <60 kg; or creatinine >133 μg/L—received 2.5 mg twice daily (n = 145), while all others received 5 mg twice daily (n = 2,247). A total of 2,392 patients were included, with median follow-up of 1.1 years. Median apixaban anti-Xa activity was 122 ng/mL (interquartile range [IQR]: 63–198 ng/mL) for the entire group; 99 ng/mL (IQR: 60–146 ng/mL) for the 2.5-mg group; and 125 ng/mL (IQR: 64–202 ng/mL) for the 5-mg group (p = 0.003). A relationship was evident between bleeding and anti-Xa activity (p = 0.01), which was driven by minor bleeding. No relationship was evident between major bleeding or stroke/systemic embolism and anti-Xa activity. In those receiving the 5-mg dose, estimated glomerular filtration rate, sex, and age had the strongest association with anti-Xa activity. Conclusion There is considerable variability in anti-Xa activity among AF patients receiving apixaban. Rates of major bleeding and stroke/systemic embolism were low irrespective of anti-Xa activity. Clinical Trial Registration ClinicalTrials.gov NCT00496769; https://clinicaltrials.gov/ct2/show/NCT00496769.

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