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

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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Rivaroxaban versus Warfarin for Prevention of Thromboembolism in Bangladeshi Patients with Non-Valvular Atrial Fibrillation

University Heart Journal ◽

10.3329/uhj.v16i2.49666 ◽

2020 ◽

Vol 16 (2) ◽

pp. 99-105

Author(s):

Golam Sodruddin ◽

Md Mukhlesur Rahman ◽

SM Ahsan Habib ◽

MSI Tipu Chowdhury ◽

Adnan Bashar ◽

...

Keyword(s):

Atrial Fibrillation ◽

Factor Xa ◽

Haemorrhagic Stroke ◽

Similar Efficacy ◽

Minor Bleeding ◽

Systemic Embolism ◽

Nonvalvular Atrial Fibrillation ◽

Safety Outcome ◽

Warfarin Group ◽

Bangladeshi Population

Background: The use of Warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulant effects than Warfarin. Methods: In this Open comparison trial, the researchers compared Rivaroxaban (at a daily dose of 20 mg or 15 mg daily in patient with a creatinine clearance of 30-49 ml/min ) with dose adjusted Warfarin (target INR 2.0 to3.0) in 2,846 patients with nonvalvular atrial fibrillation and CHA2DS2-VASc Score 2 or more. The primary efficacy outcome was stroke or systemic embolism and primary safety outcome was major or minor bleeding. This research was designed to determine whether Rivaroxaban have more efficacy and safety than Warfarin for the primary outcomes. Results: Total follow-up period was 6 months. Risk factors and co-morbidities were similar in both groups. Baseline investigations were also similar. Age and sex of both groups were matched. The rate of ischaemic stroke was 1.8% in Rivaroxaban group, as compared with 2.18% in the Warfarin group (p 0.479, nonsignificant). The rate of haemorrhagic stroke was 0.53% in Rivaroxaban group, as compared with 1.36 % in the Warfarin group (p 0.026, significant). Systemic embolism was 0.08% in Rivaroxaban group, as compared with 0.15 % in the Warfarin group (p 0.561, non-significant). The rate of major bleeding was 0.4% in Rivaroxaban group and 0.53 % in the Warfarin group (p 0.361, non-significant). The rate of minor bleeding was 2.10% in Rivaroxaban group, as compared with 2.33% in the Warfarin group (p 0.681, non-significant). Conclusions: Rivaroxaban have similar efficacy and better safety profile than Warfarin in patients with nonvalvular atrial fibrillation in Bangladeshi population. University Heart Journal Vol. 16, No. 2, Jul 2020; 99-105

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TO KNOW ABOUT THE CARDIOVASCULAR COMPLICATIONS IN WITH NON VALVULAR ATRIAL FIBRILLATION PATIENTS ON LONG TERM FOLLOW UP

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v5i1.1844 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Satyendra Sharma ◽

Keshrimal Kalwadiya

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Cardiovascular Complications ◽

Minor Bleeding ◽

Medical Sciences ◽

Nonvalvular Atrial Fibrillation ◽

Long Term Follow Up ◽

Bleeding Episodes

Background & Method: This was an observational study of patients with nonvalvular atrial fibrillation conducted at Amaltas Institute of Medical Sciences, Dewas. All 50 patients presenting to the outpatient/inpatient services of Department of Medicine and Cardiology with a diagnosis of non valvular atrial fibrillation, either chronic or paroxysmal. Result: During the course of study, 2 patients (2%) developed ischemic stroke, 12 (12%) patients were hospitalized for heart failure, 12 (12%) patients died and minor bleeding occurred in 3 (3%) patients while no patient had any major bleeding. Conclusion: No major bleeding complication occurred during study period. However, three episodes of minor bleeding occurred giving an event rate 2% per year. All the minor bleeding episodes occurred in patients taking combined warfarin and antiplatelet. Keywords: cardiovascular, non valvular atrial & fibrillation

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Oral Anticoagulation In Patients with Atrial Fibrillation. Long-Term Follow-up

Blood ◽

10.1182/blood.v116.21.4392.4392 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4392-4392

Author(s):

Cecilia Claudia Colorio ◽

Dolores Patricia Puente ◽

Andrea Silvia Rossi ◽

Gonzalo Pombo ◽

Eduardo Guevara ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Oral Anticoagulation ◽

Conflicts Of Interest ◽

Entire Group ◽

Minor Bleeding ◽

Chads2 Score ◽

Long Term Follow Up ◽

Cardiac Rhythm Disorder

Abstract Abstract 4392 Atrial fibrillation (AF) is the most common cardiac rhythm disorder and an independent risk factor for stroke. It′s prevalence in AF pts without oral anticoagulation (OA) is 1 to 12%. OA is recommended in all valvular AF pts and in non valvular AF pts associated with other risk factors for stroke (CHADS2 score >1). Objective: to evaluate characteristics, evolution and incidence of thrombosis and bleeding in pts with AF under OA for at least 3 months. Methods: we retrospectively analyzed 850 pts between Jan 2003 and Jan 2010. Results: the mean follow-up was 25 months (range 3–169). The features of the entire group are listed in the table below: Minor bleeding was observed in 32.7% of the entire group (278/850) and major bleeding in 2.7% (23/850). Most of the major bleedings occurred at the gastrointestinal tract, and 53% of those pts presented INR <2 (8/15). Fatal bleeding (located at CNS) developed in 0.2% (2/850). Ten pts developed thrombosis during the follow-up period (1.17%); 50% of them with INR < 2. Conclusion: 45% of the pts were older than 74 years and most of them disclosed valvular AF. Minor bleeding was 15.4%/year, major bleeding: 1%/year, and thrombosis: 0.42%/year, according to the current literature. Disclosures: No relevant conflicts of interest to declare.

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Dabigatran and warfarin in nonvalvular atrial fibrillation or atrial flutter in outpatient clinic practice in Brazil

Arquivos de Neuro-Psiquiatria ◽

10.1590/0004-282x20190005 ◽

2019 ◽

Vol 77 (2) ◽

pp. 80-83 ◽

Cited By ~ 1

Author(s):

Jean Michell Correia Monteiro ◽

Daniel Lordelo San-Martin ◽

Beatriz Carneiro Gondim Silva ◽

Ian Felipe Barbosa Souza ◽

Jamary Oliveira Filho ◽

...

Keyword(s):

Atrial Fibrillation ◽

Atrial Flutter ◽

Major Bleeding ◽

Thromboembolic Event ◽

Minor Bleeding ◽

Nonvalvular Atrial Fibrillation ◽

Warfarin Group ◽

Clinic Practice ◽

Prior Stroke

ABSTRACT Objectives: To compare warfarin and dabigatran for thromboembolic event prevention in patients with nonvalvular atrial fibrillation or atrial flutter. Methods: This was a retrospective cohort of participants with nonvalvular atrial fibrillation or atrial flutter using either warfarin or dabigatran in a reference center in Brazil. Results: There were 112 patients (mean age 65.5 years), with 55.3% using warfarin. The median duration of follow-up was 1.9 years for warfarin and 1.6 years for dabigatran (p = 0.167). Warfarin patients had a higher median of medical appointments per year (8.3 [6.8-10.4] vs 3.1 [2.3-4.2], p < 0.001) and the frequency of minor bleeding was more than four times higher (17.7% vs 4.0%, p = 0.035). Among patients with prior stroke, those using warfarin had 2.6 times more medical appointments for person-years of follow-up (8.5 vs 3.3). There was no major bleeding or embolic event during follow-up period. Conclusion: The dabigatran group had a lower frequency of minor bleeding and number of medical appointments than the warfarin group, without more embolic events or major bleeding.

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Patient characteristics and stroke and bleeding events in nonvalvular atrial fibrillation patients treated with apixaban and vitamin K antagonists: a Spanish real-world study

Journal of Comparative Effectiveness Research ◽

10.2217/cer-2019-0079 ◽

2019 ◽

Vol 8 (14) ◽

pp. 1201-1212 ◽

Cited By ~ 2

Author(s):

Sreeram V Ramagopalan ◽

Antoni Sicras-Mainar ◽

Carlos Polanco-Sanchez ◽

Robert Carroll ◽

Jaime F de Bobadilla

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Medical Records ◽

Vitamin K Antagonists ◽

Patient Characteristics ◽

Minor Bleeding ◽

Thromboembolic Events ◽

Systemic Embolism ◽

Bleeding Events ◽

Nonvalvular Atrial Fibrillation

Aim: To compare the risk of stroke, systemic thromboembolism and bleeding, in patients initiating apixaban or acenocoumarol for the treatment of nonvalvular atrial fibrillation. Methods: An observational, retrospective study was performed using medical records of patients who initiated apixaban or acenocoumarol between 2015 and 2017. Propensity score matching was used to match patients; stroke, systemic thromboembolism, major and minor bleeding events were compared between the matched patients. Results: Patients who were prescribed apixaban had a lower rate of systemic embolism/stroke (hazard ratio [HR] = 0.54; 95% CI: 0.38–0.78; p = 0.001), minor bleeding (HR = 0.64; 95% CI: 0.52–0.79; p < 0.001) and major bleeding (HR = 0.51; 95% CI: 0.37–0.72; p < 0.001). Conclusion: Patients prescribed apixaban for the treatment of nonvalvular atrial fibrillation had lower rates of thromboembolic events and minor/major bleeding than patients on acenocoumarol.

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All-Cause, Stroke/Systemic Embolism–, and Major Bleeding-Related Health-Care Costs Among Elderly Patients With Nonvalvular Atrial Fibrillation Treated With Oral Anticoagulants

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029617750269 ◽

2018 ◽

Vol 24 (4) ◽

pp. 602-611 ◽

Cited By ~ 5

Author(s):

Steve Deitelzweig ◽

Xuemei Luo ◽

Kiran Gupta ◽

Jeffrey Trocio ◽

Jack Mardekian ◽

...

Keyword(s):

Atrial Fibrillation ◽

Health Care ◽

Elderly Patients ◽

Health Care Costs ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Systemic Embolism ◽

Nonvalvular Atrial Fibrillation ◽

Care Costs

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Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease

Heart ◽

10.1136/heartjnl-2017-312272 ◽

2018 ◽

Vol 104 (15) ◽

pp. 1292-1299 ◽

Cited By ~ 6

Author(s):

Dragos Vinereanu ◽

Alice Wang ◽

Hillary Mulder ◽

Renato D Lopes ◽

Petr Jansky ◽

...

Keyword(s):

Atrial Fibrillation ◽

Clinical Trial ◽

Major Bleeding ◽

Treatment Effect ◽

P Value ◽

Efficacy And Safety ◽

Systemic Embolism ◽

Clinical Trial Registration ◽

Safety Outcomes ◽

Anticoagulated Patients

ObjectiveTo assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.MethodsThere were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model.ResultsPatients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory.ConclusionsIn anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.Clinical trial registrationARISTOTLE clinical trial number NCT00412984.

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Early Initiation of Direct Oral Anticoagulants After Onset of Stroke and Short- and Long-Term Outcomes of Patients With Nonvalvular Atrial Fibrillation

Stroke ◽

10.1161/strokeaha.119.028118 ◽

2020 ◽

Vol 51 (3) ◽

pp. 883-891 ◽

Cited By ~ 2

Author(s):

Tadataka Mizoguchi ◽

Kanta Tanaka ◽

Kazunori Toyoda ◽

Sohei Yoshimura ◽

Ryo Itabashi ◽

...

Keyword(s):

Atrial Fibrillation ◽

Ischemic Stroke ◽

Major Bleeding ◽

Oral Anticoagulants ◽

Direct Oral Anticoagulants ◽

Hazard Ratio ◽

Interquartile Range ◽

Systemic Embolism ◽

Nonvalvular Atrial Fibrillation ◽

Ischemic Attack

Background and Purpose— We aimed to compare outcomes of ischemic stroke patients with nonvalvular atrial fibrillation between earlier and later initiation of direct oral anticoagulants (DOACs) after stroke onset. Methods— From data for 1192 nonvalvular atrial fibrillation patients with acute ischemic stroke or transient ischemic attack in a prospective, multicenter, observational study, patients who started DOACs during acute hospitalization were included and divided into 2 groups according to a median day of DOAC initiation after onset. Outcomes included stroke or systemic embolism, major bleeding, and death at 3 months, as well as those at 2 years. Results— DOACs were initiated during acute hospitalization in 499 patients in median 4 (interquartile range, 2–7) days after onset. Thus, 223 patients (median age, 74 [interquartile range, 68–81] years; 78 women) were assigned to the early group (≤3 days) and 276 patients (median age, 75 [interquartile range, 69–82] years; 101 women) to the late (≥4 days) group. The early group had lower baseline National Institutes of Health Stroke Scale score and smaller infarcts than the late group. The rate at which DOAC administration persisted at 2 years was 85.2% overall, excluding patients who died or were lost to follow-up. Multivariable Cox shared frailty models showed comparable hazards between the groups at 2 years for stroke or systemic embolism (hazard ratio, 0.86 [95% CI, 0.47–1.57]), major bleeding (hazard ratio, 1.39 [95% CI, 0.42–4.60]), and death (hazard ratio, 0.61 [95% CI, 0.28–1.33]). Outcome risks at 3 months also did not significantly differ between the groups. Conclusions— Risks for events including stroke or systemic embolism, major bleeding, and death were comparable whether DOACs were started within 3 days or from 4 days or more after the onset of nonvalvular atrial fibrillation–associated ischemic stroke or transient ischemic attack. Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01581502.

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Approved Uses of Dabigatran Etexilate as an Anticoagulant

Journal of Pharmacy Technology ◽

10.1177/875512251102700604 ◽

2011 ◽

Vol 27 (6) ◽

pp. 258-265

Author(s):

Joshua B Darnell ◽

Erika L Kleppinger

Keyword(s):

Atrial Fibrillation ◽

Data Extraction ◽

Dabigatran Etexilate ◽

Anticoagulation Therapy ◽

Minor Bleeding ◽

Systemic Embolism ◽

Nonvalvular Atrial Fibrillation ◽

Phase 3 ◽

Study Selection ◽

Life Threatening

Objective: To review, analyze, and critique dabigatran etexilate's approved uses as an anticoagulant. Data Sources: Literature searches were performed via MEDLINE, International Pharmaceutical Abstracts, and Google Scholar through February 2011, using the term dabigatran. Additional data were obtained from tertiary sources and prescribing information. Study Selection and Data Extraction: All published Phase 3 anticoagulation trials investigating dabigatran for currently approved indications were selected. Information from other anticoagulation trials investigating dabigatran was used for critiquing Phase 3 studies. Data Synthesis: Dabigatran etexilate has been evaluated in multiple clinical trials as an alternative to enoxaparin for prevention of venous thromboembolism in total hip and knee replacement surgeries. It has also been evaluated as an alternative to warfarin in stroke and systemic embolism prevention in patients with atrial fibrillation. Results have generally been positive, with few exceptions. The standard adult dose of dabigatran 150 mg twice daily, approved for use in the US for stroke prevention in nonvalvular atrial fibrillation, was found to be superior to warfarin in regard to occurrence rates of stroke or systemic embolism and hemorrhagic stroke. The occurrence rates of intracranial bleeding, life-threatening bleeding, and major or minor bleeding were lower with dabigatran 150 mg twice daily than with warfarin; however, the occurrence of gastrointestinal bleeding was significantly higher. Conclusions: With its numerous benefits, and despite its drawbacks, dabigatran remains a promising option for oral anticoagulation therapy.

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Evaluation of Apixaban for the Treatment of Nonvalvular Atrial Fibrillation With Regard to Dosing and Safety in a Community Hospital

Journal of Pharmacy Technology ◽

10.1177/8755122517706423 ◽

2017 ◽

Vol 33 (4) ◽

pp. 140-145 ◽

Cited By ~ 2

Author(s):

Katie B. Tellor ◽

Michelle Wang ◽

Melissa S. Green ◽

Anastasia L. Armbruster

Keyword(s):

Atrial Fibrillation ◽

Community Hospital ◽

Factor Xa ◽

Retrospective Chart Review ◽

Prescribing Patterns ◽

Minor Bleeding ◽

Nonvalvular Atrial Fibrillation ◽

Hospital Design ◽

Patient Demographics ◽

Dosing Regimens

Background: Apixaban, a direct factor Xa inhibitor, is approved by the US Food and Drug Administration (FDA) for prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. Apixaban’s compelling safety and efficacy data, combined with minimal laboratory monitoring, make it an attractive anticoagulant. Objectives: To characterize and evaluate the dosing and safety of apixaban for the treatment of nonvalvular atrial fibrillation at a community hospital. Design/Patients: A retrospective chart review evaluated patients ≥18 years of age who received at least 2 consecutive doses of apixaban from January 1, 2013 to June 30, 2016. Patients with multiple admissions were evaluated for each hospitalization. Patients were excluded if height, weight, or serum creatinine was not documented during hospital admission. Patients who received apixaban for the treatment or prophylaxis of venous thromboembolism were excluded. Prescribing patterns were characterized based on FDA-approved dosing regimens and patient demographics. Safety outcomes included incidences of major, clinically relevant nonmajor, and minor bleeding. Results: Of the 707 patients evaluated, 82% received an FDA-approved apixaban regimen. Of the 127 patients (18%) who received an unapproved regimen, 5.5% (7 patients) received an unapproved frequency and 94.5% (120 patients) received an unapproved dose. The majority (98 patients, 81.7%) were underdosed. Composite bleeding rates were 2.7%, with 1.8% major bleeds, 0.7% clinically relevant nonmajor bleeds, and 0.1% minor bleeds. Conclusions: The use of apixaban must be monitored in order to ensure FDA-approved dosing regimens are being prescribed and patients are not being underdosed.

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