Risultati per: Associazione FANS e Warfarin

Annals of Internal Medicine, Volume 175, Issue 11, Page 1627-1628, November 2022.

Circulation, Volume 146, Issue Suppl_1, Page A13427-A13427, November 8, 2022. Introduction:Direct Oral Anticoagulants (DOACs) have overtaken warfarin in the treatment of non-valvular Atrial Fibrillation (AF) and venous thromboembolism (VTE). However, there is very limited data that explores the safety of DOACs for patients that are morbidly obese (BMI >40).Methods:In this multi-center retrospective study, we sought to use the Michigan Anticoagulation Quality Improvement registry (MAQI) to see how treatment of non-valvular AF or VTE with DOAC vs. warfarin affects bleeding in morbidly obese patients. Specifically, we compared average major, clinically relevant non-major (CRNM), and minor bleeding events per 100 patient years that were adjusted for statistically significant baseline characteristics (p40 included in the registry between June 2015 and September 2019. 434 patients were treated with DOACs, while 594 patients were treated with warfarin. Baseline characteristics between the two groups included age (61.5 vs 57.8, p

Circulation, Volume 146, Issue Suppl_1, Page A13987-A13987, November 8, 2022. Background:Several studies have shown the cost-effectiveness of direct oral anticoagulants (DOACs), compared with warfarin, to prevent atrial fibrillation (AF) related complications. However, few have reported cost-effectiveness of DOACs in AF patients with intermediate stroke risk. Thus, we investigated the cost-effectiveness of DOACs vs. warfarin in non-valvular AF patients with intermediate stroke risk using national representative data.Methods:We identified 7,954 newly diagnosed non-valvular AF patients (≥18 years) with intermediate stroke risk (CHA2DS2-VASc score: 1 for men and 2 for women) using the national healthcare utilization data from August 1, 2016, to July 31, 2019. Annual incidence rate of AF-related composite outcomes (heat failure, myocardial infarction, ischemic stroke, intracerebral hemorrhage, and gastrointestinal bleeding) was estimated. Cost-effectiveness was estimated using a Markov chain model with the transition probability of 1 year. The willingness-to-pay (WTP) was set at $32,000 per quality-adjusted life-year (QALY) gained.Results:The total cost of warfarin, rivaroxaban, apixaban, dabigatran and edoxaban was $2,874, $5,761, $5,151, $5,761 and $5,851, respectively. The QALYs gained were 10.83, 10.95, 11.10, 10.49 and 10.99 years, respectively. The incremental cost-effectiveness ratio of rivaroxaban, apixaban, dabigatran and edoxaban was $29,743.99, $8,426.71, -$8,483.04 and $18,483.55, respectively. The WTP was set at $32,000. DOACs (except dabigatran) were more cost-effective compared with warfarin because they did not exceed the WTP in the base-case analysis.Conclusion:Our findings showed that DOACs were more cost-effective than warfarin in non-valvular AF patients with intermediate stroke risk.Figure 1. Cost-effectiveness acceptability curve of Warfarin vs. DOACs in AF patients with intermediate stroke risk.

Circulation, Volume 146, Issue Suppl_1, Page A12863-A12863, November 8, 2022. Introduction:Left ventricular thrombus (LVT) is common post-STEMI, with an incidence of as high as 26% in patients with anterior MI. AHA guidelines recommend systemic anticoagulation with warfarin for patients with LVT. However, the efficacy of direct oral anticoagulants (DOACs) compared to warfarin in the treatment of LVT is unknown.Hypothesis:Rates of embolic events and bleeding will be similar in LVT patients treated with DOACs compared to warfarin.Methods:Retrospective single institution study of all patients with LVT diagnosed between 2010 and 2021 and treated with an anticoagulant. The primary outcome was embolic events (stroke, TIA, and other systemic embolism). Secondary outcomes were all bleeding events, major and minor bleeding per International Society on Thrombosis and Haemostasis criteria, and all adverse outcomes. p

Circulation, Volume 146, Issue Suppl_1, Page A10926-A10926, November 8, 2022. Introduction:Many prediction algorithms for warfarin maintenance dose (WD) were constructed based on the clinical and genetic information of the patients without extracorporeal circulation devices (ECDs). However, it is unclear whether might be useful for the patients with ECD, such as left ventricular assist devices (LVAD), who still require warfarin.Hypothesis:The WD algorithms constructed using non-ECD patients could be useful for LVAD patients.Methods:An observational study, the Human Genome Research Ethics Committee of OU approved (#756), was conducted at the Osaka University (OU) Hospital on 108 LVAD patients receiving warfarin therapy. Genetic polymorphisms of CYP2C9*1, *3, and VKORC1-1639G >A were tested using TaqMan genotyping assay kits. WD was defined as the administered dose during the periods when the PT-INR value was within its target range. We investigated the difference between the actual warfarin dose (AWD) and the calculated warfarin dose (CWD) using an algorithm proposed by the International Warfarin Pharmacogenetics Consortium (IWPC), which we verified with 125 Japanese non-ECD patients previously (Eur J Clin Pharmacol, 75:901).Results:The percentage of patients whose difference between CWD and AWD was within 20% of AWD showed no significant difference between the LVAD and the non-ECD (%; I, LVAD, 41.7, non-ECD, 49.6, p=0.23). The root mean squared percentage error (RMSPE) to the AWD was similar between the groups (%; LVAD, 42, non-ECD, 37). As the algorithm requires if amiodarone is concomitant with warfarin, we probed the effect of the amiodarone dose on the CWD. Interestingly, RMSPE of the LVAD with ≥ 200 mg/day of amiodarone (≥ 200A) was higher compared to those with < 200 mg/day (

Circulation, Volume 146, Issue Suppl_1, Page A13168-A13168, November 8, 2022. Introduction:In the AUGUSTUS trial, patients randomized to apixaban had lower rates of major or clinically relevant non-major (CRNM) bleeding, lower rates of death or hospitalization, and similar rates of death or ischemic events compared with warfarin. Patients randomized to aspirin (ASA) had higher rates of bleeding with similar rates of death or hospitalization, and death or ischemic event. The impact of warfarin time-in-therapeutic-range (TTR) on these outcomes is not known; however, it is plausible that sites achieving better TTR might have better outcomes with warfarin use.Methods:Using average site TTR, we assessed the hazard of bleeding, ischemic events, and death/hospitalization across quartiles of site-based TTR. These analyses were performed for both randomized strategies: apixaban vs warfarin and ASA vs placebo.Results:This analysis included data from 4420 patients at 399 sites. Site TTR was separated into quartiles of TTR (Q1: 0-49%, Q2: 42-55%, Q3: 56-69%, Q4: 70-100%). Sites with higher TTR tended to have fewer female patients (32.4% Q1 vs 25.4% Q4), more White patients (88.5% Q1 vs 97.1% Q4), and more patients previously prescribed oral anticoagulants (44.5% Q1 vs 52.5% Q4). There was no significant interaction between site TTR quartile and the hazard ratio (HR) for bleeding, death or hospitalization, or death or ischemic event with apixaban vs warfarin, or on the HR for bleeding, or death or hospitalization with ASA vs placebo (Figure). There was a borderline significant interaction (p

Circulation, Volume 146, Issue Suppl_1, Page A9301-A9301, November 8, 2022. Introduction:The effectiveness and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients with stage III chronic kidney disease (CKD) is still questioned. This study assessed the comparative effectiveness and safety of DOACs vs warfarin in stage III CKD AF patients.Methods:A cohort of patients with inpatient or outpatient coding for AF who were newly prescribed an oral anticoagulant (OAC) was created using Quebec provincial administrative databases from 2011-2017. The primary effectiveness outcome was a composite of ischemic stroke, systemic embolism and death and the primary safety outcome was a composite of intracranial, gastrointestinal and major bleeding from other sites in the first year after OAC initiation. Treatment groups were compared using inverse-probability-of-treatment-weighting Cox proportional-hazards models at under-treatment analysis.Results:14,200 qualifying patients filled a claim for a new OAC prescription; 7,592 for warfarin 1,110 for rivaroxaban 20 mg, 2,084 for apixaban 5 mg and 1,674 for apixaban 2.5 mg. Rivaroxaban 20 mg was associated with a similar composite effectiveness (hazard ratio [HR] 0.84; 95% confidence intervals [CI] 0.62-1.12) and composite safety risk (HR 1.09; 95% CI 0.74-1.62) compared to warfarin (Figure 1). Apixaban 5 mg was associated with a lower composite effectiveness (HR 0.68; 95% CI 0.53-0.86), but similar composite safety risk (HR 0.89; 95% CI 0.64-1.22), whereas apixaban 2.5 mg was associated with a similar composite effectiveness (HR 0.97; 95% CI 0.78-1.21), but lower composite safety risk (HR 0.56; 95% CI 0.37-0.85).Conclusions:In comparison to warfarin, rivaroxaban and apixaban appear to be effective and safe in stage III CKD patients with AF.

Circulation, Volume 146, Issue Suppl_1, Page A14883-A14883, November 8, 2022. Introduction:Postprocedural anticoagulation is indicated for at least 45 days in patients who undergo percutaneous left atrial appendage occlusion with the Watchman device. The relative efficacy and safety of non-vitamin K oral anticoagulants (NOACs) to warfarin for postprocedure anticoagulation in this setting is not well known.Methods:We conducted a systematic review and meta-analysis to compare NOACs with warfarin in patients who underwent left atrial appendage occlusion with Watchman. PubMed, Cochrane, and EMBASE were systematically searched. We included randomized and observational studies with at least 45 days of follow-up following Watchman implantation comparing anticoagulation with NOACs vs. warfarin for thrombotic and hemorrhagic outcomes.Results:We included 11 studies with 2,325 patients who underwent Watchman device implantation and were anticoagulated with NOACs (n=1,194; 51.35%) or warfarin (n=1,131; 48.65%). NOACs were associated with a lower incidence of major bleeding (OR 0.49; 95% CI 0.28-0.89; p=0.02; Fig. 1A) and device-related thrombosis (OR 0.44; 95% CI 0.21-0.93; p=0.03; Fig. 1B). There was no significant difference between NOACs and warfarin with regards to stroke or transient ischemic attack (OR 0.43; 95% CI 0.15-1.28; p=0.13; Fig. 2).Conclusions:In this meta-analysis, NOACs were associated with lower risks of device-related thrombosis and major bleeding relative to warfarin in patients who undergo Watchman implantation.

Circulation, Volume 146, Issue Suppl_1, Page A12361-A12361, November 8, 2022. Introduction:The efficacy and safety of non-vitamin K oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) at the extremes of body mass index (BMI) and body weight (BW) remains uncertain, leading to concerns regarding use in these populations across clinical practice guidelines.Methods:This analysis of the COMBINE-AF database pools individual patient-level data from the 4 pivotal RCTs of NOAC vs. warfarin in AF: RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48. Pts randomized to low-dose NOACs not globally approved for clinical use were excluded. The primary efficacy and safety outcome was stroke/systemic embolic event (S/SEE) and major bleeding, respectively, with intracranial hemorrhage (ICH) being a secondary outcome. Outcomes were assessed across BMI and BW using a Cox model stratified by trial, with interaction testing for NOAC vs. warfarin. Restricted cubic splines were used to display the hazard ratio of NOAC vs. warfarin for each outcome across BMI.Results:For 58,464 pts, the median BMI was 28 (25th-75th%ile: 25-32) kg/m2,with the top 5% (n=2,924) having a BMI ≥ 40 kg/m2. For patients randomized to warfarin, the risk of each outcome was lower with increasing BMI (HR per 5 kg/m2increase: S/SEE 0.79 [95% CI 0.75-0.84]; major bleeding 0.91 [95% CI 0.87-0.95]; ICH 0.72 [95% CI 0.66-0.80]; p

Introduction
Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of prior pulmonary thromboembolism (PE), caused by incomplete clot dissolution after PE. In patients with CTEPH, lifelong anticoagulation is mandatory to prevent recurrence of PE and secondary in situ thrombus formation. Warfarin, a vitamin K antagonist, is commonly used for anticoagulation in CTEPH based on historical experience and evidence. The anticoagulant activity of warfarin is affected by food and drug interactions, requiring regular monitoring of prothrombin time. The lability of anticoagulant effect often results in haemorrhagic and thromboembolic complications. Thus, lifelong warfarin is a handicap in terms of safety and convenience. Currently, the use of direct oral anticoagulants (DOACs) in CTEPH has increased with the advent of four DOACs. The safety of DOACs is superior to warfarin, with less intracranial bleeding in patients with non-valvular atrial fibrillation and venous thromboembolism. Edoxaban, the latest DOAC, also has proven efficacy and safety for those diseases in two large clinical trials; the ENGAGE-AF trial and HOKUSAI-VTE trial. The present trial seeks to evaluate whether edoxaban is non-inferior to warfarin in preventing worsening of CTEPH.

Methods and analysis
The KABUKI trial (is an investigator-initiated, multicentre, phase 3, randomised, single-blind, parallel-group, warfarin-controlled, non-inferiority trial to evaluate the efficacy and safety of edoxaban versus warfarin (vitamin K Antagonist) in subjects with chronic thromBoembolic pUlmonary hypertension taking warfarin (vitamin K antagonIst) at baseline) is designed to prove the non-inferiority of edoxaban to warfarin in terms of efficacy and safety in patients with CTEPH.

Ethics and dissemination
This study is approved by the Institutional Review Board of each participating institution. The findings will be published in a peer-reviewed journal, including positive, negative and inconclusive results.

Trial registration number
NCT04730037.

Protocol version
This paper was written per the study protocol V.4.0, dated 29 January 2021.

Objectives
To investigate effects of appropriately and inappropriately dosed apixaban/rivaroxaban versus warfarin on effectiveness and safety outcomes in patients with non-valvular atrial fibrillation (NVAF).

Design
Cohort study with nested case–control analyses using primary care electronic health records (IQVIA Medical Research Data UK database).

Setting
UK primary care.

Participants
Patients aged ≥18 years with NVAF newly prescribed apixaban (N=14 701), rivaroxaban (N=14 288) or warfarin (N=16 175) between 1 January 2012 and 30 June 2018, and followed up to 31 December 2018.

Primary and secondary outcome measures
Incident cases of ischaemic stroke/systemic embolism (IS/SE) and intracranial bleeding (ICB). Cases were matched to controls on age, sex and OAC naïve status. Using logistic regression, adjusted ORs with 95% CIs were calculated for the outcomes comparing apixaban/rivaroxaban use (appropriate or inappropriate dosing based on the product label criteria) and warfarin.

Results
For IS/SE, ORs (95% CIs) for apixaban versus warfarin were 1.19 (0.92–1.52) for appropriate dose and 1.01 (0.67–1.51) for inappropriate dose; for rivaroxaban versus warfarin, estimates were 1.07 (0.83–1.37) for appropriate dose and 1.21 (0.78–1.88) for inappropriate dose. For ICB, ORs (95% CIs) for apixaban versus warfarin were 0.67 (0.44–1.00) for appropriate dose and 0.45 (0.21–0.95) for inappropriate dose; for rivaroxaban versus warfarin, estimates were 0.81 (0.55–1.20) for appropriate dose and 1.14 (0.56–2.31) for inappropriate dose.

Conclusions
Dosing appropriateness in NVAF was not associated with a significant difference in IS/SE risk or increase in ICB risk versus warfarin. These findings may reflect residual confounding and biases that were difficult to control, as also seen in other observational studies. They should, therefore, be interpreted with caution, and prescribers should adhere to the dosing instructions in the respective Summary of Product Characteristics. Further studies on this topic from real-world populations are needed.

Stroke, Ahead of Print. Background:A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort.Methods:This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups.Results:Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140–720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51–1.73];P=0.84), death (aHR, 0.78 [95% CI, 0.22–2.76];P=0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48–1.73];P=0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15–0.82];P=0.02).Conclusions:In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

Stroke, Volume 53, Issue Suppl_1, Page A104-A104, February 1, 2022. Background:Direct oral anticoagulants (DOACs) are superior to warfarin in preventing ischemic stroke from nonvalvular atrial fibrillation (AF). Transitioning from a DOAC to warfarin is rarely medically indicated. The frequency and determinants of switching from DOAC to warfarin, including the potential influence of cost, are not known.Objective:Examine the impact of financial assistance available through Medicaid prescription coverage or low-income subsidy programs on likelihood of switching to warfarin after initiating a DOAC.Methods:We identified patients in the Medicare 5% sample who initiated a DOAC from 2015 to 2017. Patients were eligible if they were age 65 or older, had AF diagnosis, had no oral anticoagulant use during the prior 12 months, and were enrolled in a Medicare Prescription Plan for at least 12 months prior to first oral anticoagulant. Patients who switched to warfarin after an initial DOAC were identified, and their characteristics were evaluated in bivariable and multivariable analyses using Cox regression to adjust for potential confounders and censor for death or end of the observation period.Results:Of 27,151 eligible patients,16,599 (61%), 8,930 (33%), and 1,622 (6%) initiated apixaban, rivaroxaban, and dabigatran, respectively. 30% (8,110) initiated a low dose DOAC. A total of 1,481 (5.5%) switched to warfarin sometime during the follow-up period. The median time to first warfarin dose among patients who switched was 153 days. Overall, 14% of patients were eligible for Medicaid prescription coverage and an additional 8.8% were eligible for other drug subsidies; these patients were significantly less likely to switch to warfarin, compared to other patients (3.4%, 4.1%, 5.8% of patients with Medicaid coverage, other drug subsidies, or neither). After risk adjustment, the relative hazard of switching to warfarin was 0.57 (95% confidence interval (CI): 0.47-0.68) and 0.69 (95% CI: 0.56-0.85), for patients with Medicaid coverage or drug subsidy, respectively, compared to other patients.Conclusions:The financial burden of DOACs may contribute to patients switching to warfarin, despite guideline recommendations. Financial assistance may facilitate evidenced-based best practices in stroke prevention.