Study Objective
Observational studies assessing direct oral anticoagulant (DOACs) dosage in atrial fibrillation (AF) reported that a lower proportion of patients received high‐dose DOACs compared to ...those in randomized controlled trials (RCTs). Effectiveness and safety of high‐dose DOACs relative to apixaban in a real‐world AF population need to be addressed. The aim is to assess comparative effectiveness and safety of high‐dose rivaroxaban relative to apixaban.
Design
We conducted a cohort study.
Setting
We built a cohort of patients hospitalized and discharged in community with a primary or secondary AF diagnosis from 2011‐2017 using Quebec administrative databases (Med‐Echo and RAMQ).
Patients
Cohort entry was defined as the first OAC claim in new users of high‐dose rivaroxaban and apixaban, with no OAC claims in the prior year.
Intervention
To compare effectiveness and safety of high‐dose rivaroxaban to apixaban.
Measurement
We ascertained patient demographics, comorbidities, CHA2DS2‐VASc and HASBLED scores and Charlson score within 3 years prior to cohort entry. Primary effectiveness and safety were a composite of ischemic stroke/systemic thrombosis, death, myocardial infarction, and of intracranial bleeding (ICH), extracranial major bleeding, in the first year following drug initiation. We conducted propensity score matching and estimated hazard ratios (HRs) for outcomes using Cox proportional hazard models. All the analyses were conducted to account for competing risks.
Main results
The cohort consisted of 4,632 and 6,771 patients received high‐dose rivaroxaban and apixaban, respectively. High‐dose rivaroxaban users were younger with a mean age of 73.2 years, presented less associated comorbidities and had lower CHA2DS2‐VASc scores compared to apixaban. High‐dose rivaroxaban at the intention to treat was associated with a higher risk of stroke/SE/death (HR 1.21, 95% CI 1.04‐1.40) and worse composite effectiveness (HR 1.21: 1.05‐1.40); under treatment exposure, those values were at HR (1.66: 1.21‐2.29) and HR (1.58:1.19‐2.10), respectively. And, rivaroxaban presented a less favorable safety profile relative to apixaban.
Conclusion
In this study, composite effectiveness and safety varied between rivaroxaban and apixaban. High‐dose apixaban was observed to have a better effectiveness and safety.
Background Direct oral anticoagulants (DOACs) may cause false results of activated protein C resistance (APC-R) ratio. DOAC-Remove, a new reagent based on activated carbon, has been designed to ...eliminate the interference of DOACs on coagulation assays. The aim of the study was to investigate whether the use of DOAC-Remove enables to determine APC-R in patients treated with DOACs. Methods We assessed 74 venous thromboembolism (VTE) patients, including 25 on rivaroxaban, 25 on apixaban and 24 taking dabigatran. APC-R was determined using the Russell Viper Venom Time (RVVT)-based clotting test. APC-R and DOAC concentrations were tested at baseline and following DOAC-Remove. Thrombophilia, including factor V Leiden (FVL) mutation was tested. Results FVL mutation was found in 20 (27%) patients. The APC-R ratio at baseline was measurable in 43 patients (58.1%), including 20 (80%) on rivaroxaban, 19 (76%) on apixaban and four (16.7%) on dabigatran. In patients with measurable APC-R at baseline, the ratio >2.9 was found in 23 patients (53.5%). In 16 (37.2%) subjects APC-R ratio <1.8 suggested FVL mutation which was genetically confirmed. Four (9.3%) FVL carriers on dabigatran showed negative/equivocal APC-R results. In 11 (14.9%) patients taking rivaroxaban or apixaban, in whom blood was collected 2-5 h since the last dose, we observed unmeasurable APC-R. DOAC-Remove almost completely eliminated all plasma DOACs. After addition of DOAC-Remove all APC-R ratios were measurable. In four FVL carriers on dabigatran with false negative APC-R, DOAC-Remove resulted in APC-R ratios <1.8. Conclusions DOAC-Remove effectively reduces DOACs concentration in plasma, which enables FVL testing using APC-R.
The aim of this study was to compare the safety of tooth extraction in patients receiving direct oral anticoagulants (DOACs) or warfarin without cessation of their antithrombotic treatment. This ...prospective observational study included 367 patients undergoing tooth extraction (119 receiving DOACs and 248 receiving warfarin). All extractions in DOAC patients were performed 6–7h after taking DOACs in consideration of the half-life in blood under continued antithrombotic treatment. To examine the potential postoperative bleeding risk related to the time of extraction and the drug concentration of blood, activated partial thromboplastin time (APTT) in dabigatran and prothrombin time (PT) in rivaroxaban were measured three times after administration. A total of 390 tooth extractions were performed: 128 in the DOAC patients and 262 in warfarin patients. Postoperative bleeding occurred in four extractions (3.1%) in the DOAC group and in 23 (8.8%) in the warfarin group. There was no statistically significant difference between the two groups (odds ratio: 2.362, 95% confidence interval (CI) 0.819–6.815, p=0.112). APTT and PT prolongation in almost all cases decreased with time after taking the medicine. Our findings suggest that interruption of DOAC therapy is not necessary for tooth extraction if the procedure is performed at least 6h after the last dose.
Over the past 20 years, there has been a shift from vitamin K antagonists to direct oral anticoagulants (DOACs), which include the thrombin inhibitor dabigatran and the factor Xa inhibitors apixaban, ...edoxaban, and rivaroxaban. Although DOACs are associated with less serious bleeding than vitamin K antagonists, bleeding still occurs with DOACs, particularly in the elderly and in those with comorbidities. Reversal of the anticoagulant effects of the DOACs may be needed in patients with serious bleeding and in those requiring urgent surgery or intervention. Reversal can be effected with specific agents, such as idarucizumab for dabigatran and andexanet alfa for apixaban, edoxaban, and rivaroxaban, or with non-specific agents, such as prothrombin complex concentrates, activated prothrombin complex concentrate, and recombinant activated factor VII. This paper (i) provides an update on when and how to reverse the DOACs, (ii) describes new reversal agents under development, and (iii) provides a strategic framework for the reversal of the factor XI inhibitors currently under investigation in phase three clinical trials.
Background: Apixaban is a direct oral anticoagulant (DOAC) for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (NVAF). Other DOACs require renal dose ...adjustments based solely on creatinine clearance. Apixaban differs in that its dose adjustments are more complex, potentially leading to prescribing errors. Objective: To determine if adherence to Food and Drug Administration (FDA)-approved dosing for apixaban is maintained in hospitalized patients with NVAF. Methods: Patients ≥18 years old with NVAF who received apixaban during admission to 1 of 3 hospitals were evaluated. The primary outcome was to determine if providers order apixaban in accordance with FDA-approved dosages. Secondary outcomes included determining if pharmacist review increased the number of orders in accordance with FDA-approved dosing, which of the 3 criteria (age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL) were met in patients receiving off-label dosing, and the rationale for off-label prescribing. Results: A total of 556 patients met inclusion criteria. Apixaban was dosed according to FDA labeling by providers in 83.4% (n = 464) of orders. After pharmacist review, 87.0% (n = 484) of orders were at the approved dose, 12.2% (n = 68) were underdosed, and 0.7% (n = 4) were overdosed. Most patients who were underdosed met only 1 dose reduction criterion—most commonly age ≥80 years (56.0%). Reasons for off-label dosing included home dose continuation (39.0%), history of or perceived bleeding risk (30.5%), or unspecified/other (30.5%). Conclusions: The majority of apixaban orders for NVAF were based on FDA-approved dosages after provider entry and pharmacist review.
Direct oral anticoagulants (DOACs) are increasingly used in the treatment and prophylaxis of thromboembolism because of several advantages over vitamin K antagonists, including no need for laboratory ...monitoring. However, it has become increasingly important in certain clinical scenarios to know either actual DOAC concentration (quantitative) or presence of DOAC (qualitative). These clinical conditions include patients presenting with major bleeding or requiring urgent surgery who may need a reversal or hemostatic agent, extremes of body weight, failed therapy, etc. Prothrombin time and activated partial thromboplastin time are variably affected by factor Xa inhibitors (FXaIs) and direct thrombin inhibitor (DTI), respectively, depending on reagents' sensitivity, and hence, they cannot be relied on confidently. Thrombin time is highly sensitive to very low amounts of DTI; thus, normal value rules out a clinically significant amount. Liquid chromatography mass spectrometry accurately measures DOAC levels but is clinically impractical. Dilute thrombin time and ecarin-based assays using appropriate calibrators/controls provide an accurate DTI level. Anti-Xa assay using corresponding FXaI calibrators/controls provides accurate drug levels. However, these assays are not readily available in the United States compared with some other parts of the world. Heparin assays using anti-Xa activity often have a linear relationship with calibrated FXaI assays, especially at the lower end of on-therapy levels, and they may provide rapid assessment of drug activity for clinical decision making. Currently, there is very limited knowledge of DOAC effect on viscoelastic measurements. Although there is uniformity in expression of DOAC concentrations in nanograms per milliliter, a universal FXaI DOAC assay is urgently needed.
Background:
Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia type. Patients with AF are often administered anticoagulants to reduce the risk of ischemic stroke due to an irregular ...heartbeat. We evaluated the efficacy and safety of edoxaban
versus
warfarin in patients with nonvalvular AF by conducting an updated meta-analysis of real-world studies.
Methods:
In this comprehensive meta-analysis, we searched two databases, PubMed and EMBASE, and included retrospective cohort observational studies that compared edoxaban with warfarin in patients with nonvalvular AF from 1 January 2009, to 30 September 2023. The effectiveness and safety outcomes were ischemic stroke and major bleeding, respectively. In the final analysis, six retrospective observational studies involving 87,236 patients treated with warfarin and 40,933 patients treated with edoxaban were included. To analyze the data, we used a random-effects model to calculate the hazard ratio (HR).
Results:
Patients treated with edoxaban had a significantly lower risk of ischemic stroke hazard ratio (HR) = 0.66; 95% confidence interval (CI) = 0.61–0.70;
p
< 0.0001 and major bleeding (HR = 0.58; 95% CI = 0.49–0.69;
p
< 0.0001) than those treated with warfarin. The sensitivity analysis results for ischemic stroke and major bleeding were as follows: HR = 0.66; 95% CI = 0.61–0.70;
p
< 0.0001 and HR = 0.58; 95% CI = 0.49–0.69;
p
< 0.0001, respectively.
Conclusion:
Our findings revealed that edoxaban performed better than warfarin against major bleeding and ischemic stroke.
Cancer patients are at an increased risk of developing atrial fibrillation (AF) and thrombosis. However, the management of anticoagulation in patients with both diseases may be challenging, and data ...on these patients are lacking. We summarize the current evidence on the incidence and prevalence of cancer in AF and vice versa and provide some practical considerations on the management of oral anticoagulation in specific clinical situations. Low-molecular weight heparins are not approved for thromboprophylaxis in AF, and management of warfarin can be difficult. The use of direct oral anticoagulants may be particularly attractive for their rapid onset/offset action and lower bleeding risk.
Patient's adherence to oral anticoagulant therapy is essential to prevent and treat thrombotic events.
To assess the patients' adherence Morisky Medication Adherence Scale 8-items was used. The ...target population included 785 consecutive outpatients, of whom 384 were on Vitamin K Antagonists and 401 on Direct Oral Anticoagulants. Moreover, we evaluate which variable among age, gender, having experienced a thrombotic episode, time in the therapeutic range for patients on Vitamin K Antagonists, being naive and once versus twice daily drug assumption for patients on Direct Oral Anticoagulants, could affect adherence to therapy.
Morisky Medication Adherence Scale 8-items score was 8 in both groups. The intentional non-adherence obtained the lowest score while the unintentional non-adherence is the most frequent problem in patients treated with either Vitamin K Antagonists or Direct Oral Anticoagulants. Age > 75 years, male gender, having experienced a thrombotic episode, being naive and assuming Direct Oral Anticoagulants twice a day were significantly associated with a higher risk to forget assuming the oral anticoagulant, to have more difficulty in remembering to take it or to bring it in case of travel or leaving home. A low percentage of time in therapeutic range was associated with a not regularly assumption of the anticoagulants.
Patients treated with Vitamin K Antagonists or Direct Oral Anticoagulants show a good adherence and persistence to their oral anticoagulant therapy. Several factors have been identified to affect patients' adherence and deserve a careful attention by the doctors at the Anticoagulation Clinic.
•Adherence to both oral anticoagulants VKAs and DOACs is good in patients followed-up in an Anticoagulation Clinic.•There was no difference in the adherence to therapy between patients treated with AVKs and those treated with DOACs.•The non-intentional non-adherence is the most frequent problem in patients treated with either VKAs or DOACs.•Aging, male gender, time in range <70% and a previous thrombotic event may affect adherence of patients on VKAs.•Aging, being naïve and twice daily drug assumption may affect adherence to therapy of patients on DOACs.
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