low-dose apixaban criteria

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The primary safety endpoint was major bleeding. Clarithromycin (500 mg, twice a day), an inhibitor of P-gp and a strong inhibitor of CYP3A4, led to a 1.6-fold and 1.3-fold increase in mean apixaban AUC and Cmax respectively. Increasing age may increase haemorrhagic risk (see section 5.2). In the apixaban vs warfarin study the incidence of ISTH major gastrointestinal bleeds (including upper GI, lower GI, and rectal bleeding) with apixaban was 0.76%/year. 4. Apixaban also demonstrates anti-Factor Xa activity as evident by reduction in Factor Xa enzyme activity in multiple commercial anti-Factor Xa kits, however results differ across kits. The use of apixaban may be associated with an increased risk of occult or overt bleeding from any tissue or organ, which may result in posthaemorrhagic anaemia. Common adverse reactions were haemorrhage, contusion, epistaxis, and haematoma (see Table 2 for adverse reaction profile and frequencies by indication). Date of first authorisation: 01 January 2021, Bristol-Myers Squibb House, Uxbridge Business Park, Sanderson Road, Uxbridge, Middlesex, UB8 1DH, UK. anti-Factor Xa activity max (IU/mL), Apix. Apixaban should be used with caution when coadministered with SSRIs/SNRIs, NSAIDs, ASA and/or P2Y12 inhibitors because these medicinal products typically increase the bleeding risk (see section 4.4). The program was designed to demonstrate the efficacy and safety of apixaban for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) and one or more additional risk factors, such as: prior stroke or transient ischaemic attack (TIA), symptomatic heart failure (NYHA Class II). As a precautionary measure, it is preferable to avoid the use of apixaban during pregnancy. For VKA, additional analyses using subgroups by TTR showed that the highest rate of bleeding was associated with the lowest quartile of TTR. HHS Vulnerability Disclosure, Help Patients can continue apixaban use while undergoing catheter ablation (see sections 4.3, 4.4 and 4.5). The PK/PD relationship observed in patients was consistent with that established in healthy subjects. J Am Coll Cardiol. Bookshelf Both employed the same dose-reduction criteria for apixaban. Concomitant use of ASA increased the risk of ISTH (International Society on Thrombosis and Hemostasis) major or CRNM (Clinically Relevant Non-Major) bleeding in apixaban-treated subjects from 16.4% per year to 33.1% per year (see section 5.1). Patients were randomised up to 14 days after the ACS and/or PCI to either apixaban 5 mg twice daily (2.5 mg twice daily if two or more of the dose-reduction criteria were met; 4.2% received lower dose) or VKA and to either ASA (81 mg once daily) or placebo. 7. TCTMD All rights reserved. Reversal of apixaban pharmacodynamic effects, as demonstrated by changes in the thrombin generation assay, was evident at the end of infusion and reached baseline values within 4 hours after the start of a 4-factor PCC 30 minute infusion in healthy subjects. In the AMPLIFY study a total of 5,395 patients were randomised to treatment with apixaban 10 mg twice daily orally for 7 days followed by apixaban 5 mg twice daily orally for 6 months, or enoxaparin 1 mg/kg twice daily subcutaneously for at least 5 days (until INR 2) and warfarin (target INR range 2.0-3.0) orally for 6 months. There was no impact of impaired renal function on peak concentration of apixaban. Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. After combined administration of enoxaparin (40 mg single dose) with apixaban (5 mg single dose), an additive effect on anti-Factor Xa activity was observed. The mean age was 69.1 years, the mean CHADS2 score was 2.1 and 18.9% of patients had prior stroke or TIA. * Assessed by sequential testing strategy designed to control the overall type I error in the trial. The first dose of apixaban was given 12 to 24 hours post-surgery, whereas enoxaparin was started 9 to 15 hours prior to surgery. Reduced-dose apixaban is recommended in patients fulfilling 2 of 3 criteria: age 80 years, body weight 60 kg, and serum creatinine 1.5 mg/dL. 2016 Nov;129(11):1198-1204. doi: 10.1016/j.amjmed.2016.05.041. Apixaban is dear to me, but dearer still is warfarin. Thus, of 11,928 patients randomized to receive apixaban in the 2 trials, only 607 (5.1%) received the lower dose (1,2). Thus, Bhagirath et al. The European Medicines Agency has deferred the obligation to submit the results of studies with Eliquis in one or more subsets of the paediatric population in venous and arterial embolism and thrombosis (see section 4.2 for information on paediatric use). The overall discontinuation rate due to adverse reactions was 1.8% for apixaban and 2.6% for warfarin in the ARISTOTLE study. transesophageal echocardiography (TEE) or computed tomographic scan (CT)) prior to cardioversion should be considered, in accordance with established medical guidelines. Low body weight (< 60 kg) may increase haemorrhagic risk (see section 5.2). The initial dose should be taken 12 to 24 hours after surgery. It definitely tells you that you should not use apixaban 2.5 mg twice daily in individuals who dont have the criteria for it. Copyright 2021 Elsevier Inc. All rights reserved. ARISTOTLE data include patients who received apixaban placebo but exclude patients incorrectly dosed. If surgery or invasive procedures cannot be delayed, appropriate caution should be exercised, taking into consideration an increased risk of bleeding. After 2 days of coadministration of Eliquis with VKA therapy, an INR should be obtained prior to the next scheduled dose of Eliquis. The recommended duration of treatment is 10 to 14 days. J Am Coll Cardiol 2020;75:1145-1155. Join our newsletter! Both studies were randomised, parallel-group, double-blind, multinational trials in patients with symptomatic proximal DVT or symptomatic PE. Any unused medicinal product or waste material should be disposed of in accordance with local requirements. The rate of bleeding was similar between apixaban and the highest quartile of TTR. (6) will be welcomed by clinicians, but an important knowledge gap remains concerning the appropriateness of the unexpectedly frequent use of apixaban 2.5 mg twice daily in clinical practice. It remains possible that such patients are best treated with the lower dose of apixaban, even if they do not meet the criteria for dose reduction used in the trials. Table 5: Bleeding results from pivotal phase III studies*, * All the bleeding criteria included surgical site bleeding, 1 Includes events occurring after first dose of enoxaparin (pre-surgery), 2 Includes events occurring after first dose of apixaban (post-surgery). As a result of FXa inhibition, apixaban prolongs clotting tests such as prothrombin time (PT), INR and activated partial thromboplastin time (aPTT). The risk of these events may be increased by the post-operative use of indwelling epidural catheters or the concomitant use of medicinal products affecting haemostasis. Table 9: Bleeding events in patients with atrial fibrillation in the AVERROES study. Apixaban has not been studied in clinical studies in patients undergoing hip fracture surgery to evaluate efficacy and safety in these patients. Apixaban demonstrated a statistically superior reduction in the primary endpoint, a composite of all VTE/all cause death, and in the Major VTE endpoint, a composite of proximal DVT, non-fatal PE, and VTE-related death, compared to enoxaparin in both elective hip or knee replacement surgery (see Table 4). Table 11: Bleeding results in the AMPLIFY study. Crushed Eliquis tablets are stable in water, G5W, apple juice, and apple puree for up to 4 hours. For patients initiating treatment with apixaban, 5 mg should be given twice daily for at least 2.5 days (5 single doses) before cardioversion to ensure adequate anticoagulation (see section 5.1). (6) report pharmacokinetic, pharmacodynamic, and outcome data from the ARISTOTLE trial for 751 patients correctly allocated apixaban/placebo 2.5 mg twice daily compared with 17,322 patients correctly allocated apixaban/placebo 5 mg twice daily according to the dosing criteria detailed in the study protocol (6). In patients with creatinine clearance < 15 mL/min, or in patients undergoing dialysis, there is no clinical experience therefore apixaban is not recommended (see sections 4.2 and 5.2). It allows continued monitoring of the benefit/risk balance of the medicinal product. AVERROES was stopped early based on a recommendation by the independent Data Monitoring Committee due to clear evidence of reduction of stroke and systemic embolism with an acceptable safety profile. One of the possible reasons for the frequent use of apixaban 2.5 mg twice daily in the community might be that clinicians are increasingly anticoagulating AF patients who would not have been eligible for inclusion in the trials, and in an attempt to mitigate bleeding risk are choosing the lower dose of apixaban even when they do not meet the trial criteria for dose reduction. Apixaban has become one of the most widely used direct oral anticoagulants worldwide for stroke prevention in patients with atrial fibrillation (AF) after randomized trials demonstrated its superior efficacy and safety compared with warfarin, and its superior efficacy and similar safety compared with aspirin, for this indication (1,2). It is not recommended in patients with severe hepatic impairment (see section 5.2). Eliquis is contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk (see section 4.3). Start typing to retrieve search suggestions. Pharmacokinetic/pharmacodynamic relationship. In rat milk, a high milk to maternal plasma ratio (Cmax about 8, AUC about 30) was found, possibly due to active transport into the milk. Prevention of VTE in adult patients who have undergone elective hip or knee replacement surgery (VTEp), Prevention of stroke and systemic embolism in adult patients with NVAF, with one or more risk factors (NVAF), Treatment of DVT and PE, and prevention of recurrent DVT and PE (VTEt), Hypersensitivity, allergic oedema and Anaphylaxis, Eye haemorrhage (including conjunctival haemorrhage), Hypotension (including procedural hypotension), Respiratory, thoracic and mediastinal disorders, Liver function test abnormal, asparate aminotransferase increased, blood alkaline phosphatase increased, blood bilirubin increased, Musculoskeletal and connective tissue disorders, Abnormal vaginal haemorrhage, urogenital haemorrhage, General disorders and administration site conditions, Injury, poisoning and procedural complications, Post procedural haemorrhage (including post procedural haematoma, wound haemorrhage, vessel puncture site haematoma and catheter site haemorrhage), wound secretion, incision site haemorrhage (including incision site haematoma), operative haemorrhage, * There were no occurrences of generalised pruritus in CV185057 (long term prevention of VTE). official website and that any information you provide is encrypted In patients taking apixaban for the treatment of DVT and PE or prevention of recurrent DVT and PE, the results demonstrate a less than 2.2-fold fluctuation in peak-to-trough levels. Therefore, haemodialysis is unlikely to be an effective means of managing apixaban overdose. For the prevention of stroke and systemic embolism in patients with NVAF, patients with severe renal impairment (creatinine clearance 15-29 mL/min), and patients with serum creatinine 1.5 mg/dL (133 micromole/L) associated with age 80 years or body weight 60 kg should receive the lower dose of apixaban 2.5 mg twice daily (see section 4.2). To bookmark a medicine you must sign up and log in. Table 7: Secondary endpoints in patients with atrial fibrillation in the ARISTOTLE study. . The incidence of ISTH major gastrointestinal bleeds (including upper GI, lower GI, and rectal bleeding) was 0.76%/year with apixaban and 0.86%/year with warfarin. (6) are remarkably consistent with those reported from the AVERROES trial (Table 1). Following administration of a crushed 5 mg apixaban tablet suspended in 60 mL of G5W and delivered via a nasogastric tube, exposure was similar to exposure seen in other clinical studies involving healthy subjects receiving a single oral 5 mg apixaban tablet dose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Prevention of recurrent DVT and/or PE following completion of 6 months of treatment for DVT or PE. The dosing regimen should be reduced to a 5 mg loading dose followed by 2.5 mg twice daily if the patient meets the criteria for dose reduction (see above sections Dose reduction and Renal impairment). In patients undergoing hip replacement surgery. The absolute bioavailability of apixaban is approximately 50% for doses up to 10 mg. Apixaban is rapidly absorbed with maximum concentrations (Cmax) appearing 3 to 4 hours after tablet intake. One of the possible reasons for the frequent use of apixaban 2.5 mg twice daily in the community might be that clinicians are increasingly anticoagulating atrial fibrillation patients who would not have been eligible for inclusion in the trials, and in an attempt to mitigate bleeding risk are choosing the lower dose of apixaban even when they do not meet the trial criteria for dose reduction., Though the data from the current paper should be reassuring to clinicians who treat patients who would have been eligible for ARISTOTLTE according to the dosing criteria, we urgently need additional data on the optimal dosing of apixaban in patients with atrial fibrillation who have clinical characteristics that may place them at very high risk of drug overexposure and bleeding, and which would have excluded them from the ARISTOTLE and AVERROES trial, Eikelboom and colleagues write. By inhibiting factor Xa, apixaban prevents thrombin generation and thrombus development. Bhagirath et al. Most apixaban-treated patients received the standard dose of 5.0 mg twice daily, but those who had at least two of three characteristics expected to be associated with increased exposure to the drug (age 80 or older, weight 60 kg or less, and creatinine 1.5 mg/dL or greater) received a half dose. Specifically, in apixaban-treated patients, major or CRNM bleeding occurred in 157 (13.7%), and 84 (7.4%) patients in the ASA arm and in the placebo arm respectively. Therefore, it is not recommended in these patients. Mean half-life of apixaban decreased from 13.4 hours when apixaban was administered alone to 5.3 hours and 4.9 hours, respectively, when activated charcoal was administered 2 and 6 hours after apixaban. Santos J., Antonio N., Rocha M., Fortuna A. In the apixaban group, 342 patients received a loading dose (331 patients received the 10 mg dose and 11 patients received the 5 mg dose). If a dose is missed, the patient should take Eliquis immediately and then continue with twice daily intake as before. No dose adjustment for apixaban is required when coadministered with agents that are not strong inhibitors of both CYP3A4 and P-gp. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from apixaban therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. But the relative impact of apixaban versus warfarin did not differ by dose for stroke or systemic embolism, major bleeding, or mortality (, In an accompanying editorial, John Eikelboom, MBBS (Population Health Research Institute and McMaster University, Hamilton, Canada), and colleagues note that the lower 2.5-mg dose of apixaban is used much more widely in everyday practice than it was in ARISTOTLE and. Heart Vessels. Depending on local availability, a consultation of a coagulation expert should be considered in case of major bleedings. The mean age was 69.9 years, 94% of patients randomised had a CHA2DS2-VASc score > 2, and 47% had a HAS-BLED score > 3. Discontinuing anticoagulants, including apixaban, for active bleeding, elective surgery, or invasive procedures places patients at an increased risk of thrombosis. According to the ARISTOTLE and AVERROES trial protocols, the majority of patients received apixaban at the standard dose of 5 mg twice daily, and only those who met at least 2 of 3 criteria for dose reduction (age 80 years, body weight 60 kg, and creatinine level 1.5 mg/dl or 133 mol/l) received the lower dose of 2.5 mg twice daily. Disclaimer, National Library of Medicine Therefore, the use of apixaban is not recommended in this setting. Epub 2021 Jan 24. What are the implications of this report for clinical practice? The primary safety endpoint was major bleeding during the treatment period. The safety and efficacy of Eliquis in children and adolescents below age 18 have not been established. G Ital Cardiol (Rome). There are no data from the use of apixaban in pregnant women. The site is secure. Following surgery, other platelet aggregation inhibitors are not recommended concomitantly with apixaban (see section 4.5). This includes interventions for which the probability of clinically significant bleeding cannot be excluded or for which the risk of bleeding would be unacceptable. 2015 Feb;38(2):153-4. doi: 10.1111/pace.12570. In studies conducted in healthy subjects, as described below, apixaban did not meaningfully alter the pharmacokinetics of digoxin, naproxen, or atenolol. The mean age was 56.7 years and 91.7% of randomised patients had unprovoked VTE events. In a clinical study in atrial fibrillation patients, diminished efficacy and a higher risk of bleeding were observed with coadministration of apixaban with strong inducers of both CYP3A4 and P-gp compared with using apixaban alone. No changes were observed in the effect of naproxen on arachidonic acid-induced platelet aggregation and no clinically relevant prolongation of bleeding time was observed after concomitant administration of apixaban and naproxen. 1. Am J Med. Epub 2016 Jun 21. The incidence of ISTH major intraocular bleeding with apixaban was 0.18%/year. This analysis included only those patients who received the appropriate dose of study drug (n = 18,073). No dose adjustment for apixaban is required during concomitant therapy with such medicinal products, however in patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp apixaban should be used with caution for the prevention of VTE in elective hip or knee replacement surgery, for the prevention of stroke and systemic embolism in patients with NVAF and for the prevention of recurrent DVT and PE. Dr. Chan has reported that he has no relationships relevant to the contents of this paper to disclose. All rights reserved. "Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients: comparative effectiveness and safety evaluated using a propensity-score-matched approach". Apixaban efficacy for prevention of a recurrence of a VTE was maintained across subgroups, including age, gender, BMI, and renal function. , the latter of which compared apixaban and aspirin in A-fib patients who were unsuitable for warfarin. In the study, apixaban was statistically superior to enoxaparin/warfarin in the primary safety endpoint [Relative Risk 0.31, 95% confidence interval (0.17, 0.55), P-value <0.0001] (see Table 11). Continue typing to refine. This content is available for meeting attendees and/or Platinum Members. The two doses of apixaban also provided comparable reductions in major bleeding relative to warfarin in their respective groups, lead author Michel Zeitouni, MD (Duke Clinical Research Institute, Durham, NC), told TCTMD. Stroke 2019;50:110-118. In the ASA versus placebo comparison, the primary safety endpoint of ISTH major or CRNM bleeding at month 6 occurred in 367 (16.1%), and 204 (9.0%) patients in the ASA arm and in the placebo arm respectively (HR=1.88, 95% CI: 1.58, 2.23; two-sided p<0.0001). Coadministration of apixaban 10 mg with atenolol 100 mg did not have a clinically relevant effect on the pharmacokinetics of apixaban. Dr. Wheeler has been supported by educational grants from The Royal Australasian College of Physicians and Rotary International. Alu PVC/PVdC perforated unit dose blisters of 60x1 and 100x1 film-coated tablets. Active clinically significant bleeding. In a study comparing 8 subjects with mild hepatic impairment, Child-Pugh A score 5 (n = 6) and score 6 (n = 2), and 8 subjects with moderate hepatic impairment, Child-Pugh B score 7 (n = 6) and score 8 (n = 2), to 16 healthy control subjects, the single-dose pharmacokinetics and pharmacodynamics of apixaban 5 mg were not altered in subjects with hepatic impairment. The data reported by Zeitouni et al will be welcomed by clinicians, but an important knowledge gap remains concerning the appropriateness of the unexpectedly frequent use of apixaban 2.5 mg twice daily in clinical practice. Therefore, haemodialysis is unlikely to be an effective means of managing apixaban overdose. sharing sensitive information, make sure youre on a federal In the NVAF studies, the overall incidence of adverse reactions related to bleeding with apixaban was 24.3% in the apixaban vs warfarin study and 9.6% in the apixaban vs acetylsalicylic acid study. A clinical study enrolled patients with atrial fibrillation with ACS and/or undergoing PCI and a planned treatment period with a P2Y12 inhibitor, with or without ASA, and oral anticoagulant (either apixaban or VKA) for 6 months. Apixaban can be taken with or without food. In patients with mild or moderate renal impairment, the following recommendations apply: - for the prevention of VTE in elective hip or knee replacement surgery (VTEp), for the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt), no dose adjustment is necessary (see section 5.2). Accessibility The primary objective of AUGUSTUS was to assess safety, with a primary endpoint of ISTH major or CRNM bleeding. Alexander reports having received research grants from Bristol-Myers Squibb, Boehringer Ingelheim, AstraZeneca, CryoLife, CSL Behring, the US Food and Drug Administration, the National Institutes of Health, Sanofi, and VoluMetrix, as well as consulting fees from Pfizer, Bristol-Myers Squibb, AbbVie Pharmaceuticals, CSL Behring, Novo Nordisk, Portola Pharmaceuticals, Quantum Genomics, Teikoku Pharmaceuticals, VA Cooperative Studies, and Zafgen. There is limited experience of co-administration with other platelet aggregation inhibitors (such as GPIIb/IIIa receptor antagonists, dipyridamole, dextran or sulfinpyrazone) or thrombolytic agents. If cardioversion is required before 5 doses of apixaban can be administered, a 10 mg loading dose should be given, followed by 5 mg twice daily. government site. Coadministration of single doses of apixaban (10 mg) and naproxen (500 mg), a commonly used NSAID, did not have any effect on the naproxen AUC or Cmax. All patients received background therapy with a P2Y12 inhibitor (clopidogrel: 90.3%) prescribed per local standard of care. Pharmacokinetic or pharmacodynamic interactions were not evident when apixaban was coadministered with ASA 325 mg once a day. Eliquis should be swallowed with water, with or without food. The duration of overall therapy should be individualised after careful assessment of the treatment benefit against the risk for bleeding (see section 4.4). "Apixaban versus warfarin in patients with atrial fibrillation". To view the changes to a medicine you must sign up and log in. In the ARISTOTLE study a total of 18,201 patients were randomised to double-blind treatment with apixaban 5 mg twice daily (or 2.5 mg twice daily in selected patients [4.7%], see section 4.2) or warfarin (target INR range 2.0-3.0), patients were exposed to study active substance for a mean of 20 months. Despite the attractive results with apixaban in the randomized trials, there has been uncertainty about use of the 2.5-mg twice-daily dose of apixaban in the community. ARISTOTLE was funded by Bristol-Myers Squibb and Pfizer. "Clinical and pharmacological effects of apixaban dose adjustment in the ARISTOTLE trial". In healthy subjects, administration of activated charcoal 2 and 6 hours after ingestion of a 20 mg dose of apixaban reduced mean apixaban AUC by 50% and 27%, respectively, and had no impact on Cmax. When suggestions are available use up and down arrows to review and ENTER to select. In the absence of other criteria for dose reduction (age, body weight), no dose adjustment is necessary (see section 5.2). Granger C.B., Alexander J.H., McMurray J.J.V., "Apixaban versus warfarin in patients with atrial fibrillation", "Apixaban in patients with atrial fibrillation", "Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients: comparative effectiveness and safety evaluated using a propensity-score-matched approach", "Outcomes after use of standard- and low-dose non vitamin k antagonist oral anticoagulants in Asian patients with atrial fibrillation". Treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt). Care is to be taken if patients are treated concomitantly with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs), or non-steroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid. Indwelling epidural or intrathecal catheters must be removed at least 5 hours prior to the first dose of apixaban. The recommended dose of apixaban is 2.5 mg taken orally twice daily. In a clinical study of patients with atrial fibrillation, concomitant use of ASA increased the major bleeding risk on apixaban from 1.8% per year to 3.4% per year and increased the bleeding risk on warfarin from 2.7% per year to 4.6% per year. If neurological compromise is noted, urgent diagnosis and treatment is necessary. Unable to load your collection due to an error, Unable to load your delegates due to an error. For patients randomised to warfarin, the median percentage of time in therapeutic range (TTR) (INR 2-3) was 66%. Table 8: Key efficacy outcomes in patients with atrial fibrillation in the AVERROES study, Stroke, systemic embolism, MI, or vascular death*. The overall incidence of adverse reactions related to bleeding with apixaban was 10% in the apixaban vs enoxaparin studies. In vitro apixaban studies showed no inhibitory effect on the activity of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2D6 or CYP3A4 (IC50 > 45 M) and weak inhibitory effect on the activity of CYP2C19 (IC50 > 20 M) at concentrations that are significantly greater than peak plasma concentrations observed in patients. The apixaban clinical program was designed to demonstrate the efficacy and safety of apixaban for the prevention of VTE in a broad range of adult patients undergoing elective hip or knee replacement. 2021 Jul;36(7):1035-1046. doi: 10.1007/s00380-021-01777-3. Of those, 4.2% met dose-reduction criteria. A total of 8,464 patients were randomised in two pivotal, double-blind, multi-national studies, comparing apixaban 2.5 mg given orally twice daily (4,236 patients) or enoxaparin 40 mg once daily (4,228 patients). Statistically significant superiority was also achieved in the key secondary endpoints of both major bleeding and all-cause death (see Table 7). For patients randomised to VKA, the proportion of time in therapeutic range (TTR) (INR 2-3) was 56%, with 32% of time below TTR and 12% above TTR. In VKA-treated patients, major or CRNM bleeding occurred in 208 (18.5%), and 122 (10.8%) patients in the ASA arm and in the placebo arm respectively. "Impact of direct oral anticoagulants off-label doses on clinical outcomes of atrial fibrillation patients: a systematic review". The overall discontinuation rate due to adverse reactions was 1.5% for apixaban and 1.3% for ASA in the AVERROES study. Efficacy across subgroups, including age, gender, body mass index (BMI), renal function, extent of index PE, location of DVT thrombus, and prior parenteral heparin use was generally consistent. It gives us another platform to talk about [that question] but doesnt directly address it and shouldnt reassure people about using the lower dose in people who dont meet the criteria, he advised. Baseline characteristics and drug levels according to apixaban dosing in ARISTOTLE as presented by Zeitouni et al. Pharmacotherapeutic group: Antithrombotic agents, direct factor Xa inhibitors, ATC code: B01AF02. Alu-PVC/PVdC blisters. The relationship between apixaban plasma concentration and anti-Factor Xa activity was best described by a linear model. But the relative impact of apixaban versus warfarin did not differ by dose for stroke or systemic embolism, major bleeding, or mortality (P for interaction = NS for all).

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