Time In Therapeutic Range Research Articles

Appropriate Use of Anticoagulants among Nonvalvular Atrial Fibrillation Patients at a University Hospital in Thailand

OBJECTIVE: Warfarin is primarily used for stroke prevention in atrial fibrillation (AF) patients in Thailand. Novel oral anticoagulants (NOACs) are used less commonly due to their high cost. This study aimed to evaluate the appropriate use of anticoagulants and clinical outcomes among nonvalvular AF (NVAF) patients. METHODS: This retrospective study collected data from the electronic medical records of patients who were diagnosed with NVAF between January 2014 and December 2019 at the Faculty of Medicine, Vajira Hospital. Baseline characteristics, prescribed indication, types and doses of anticoagulant, and ischemic and hemorrhagic outcomes were recorded and analyzed. RESULTS: We analyzed 783 patients with NVAF in this study. Of these, 539 (68.90%) were treated with oral anticoagulants (OAC), including 344 patients (43.90%) with warfarin therapy and 195 (24.90%) with NOACs. Meanwhile, 492 (73.10%) patients with CHA2DS2VASC score ≥ 2 received OAC therapy that was suitable for their indication. Of the 344 patients who received warfarin, 112 patients (32.60%) had an optimal time in therapeutic range (TTR) level of ≥ 65%. Of the 195 NOAC patients, only 98 (50.30%) received appropriate doses of NOACs. There was no statistically significant difference in the overall incidence rates of ischemic stroke/systemic embolism, bleeding, cardiovascular death, and all-cause death between the warfarin and NOACS groups. Appropriate TTR levels in the warfarin group was associated with significantly lower incidence rates of cardiovascular death (hazard ratio: 0.14; 95% CI: 0.02–0.79; p = 0.02) and all-cause death (hazard ratio: 0.36; 95% CI: 0.12–0.87; p = 0.01), than inappropriate TTR levels. CONCLUSION: Most NVAF patients received oral anticoagulants with the appropriate indication. Warfarin is the most prescribed oral anticoagulant for patients with NVAF. About half of the patients received inappropriate doses of oral anticoagulants that potentially adversely affected the study outcomes of cardiovascular and all-cause deaths.

Effectiveness and Safety of the Coadministration of Rifampin and Warfarin versus Direct Oral Anticoagulants: A Cohort Study.

Pharmacokinetic studies have shown that rifampin reduces the levels of oral anticoagulants during the initiation of coadministration, raising concerns about an increased thrombotic risk, but there are limited comparative clinical outcomes between rifampin and warfarin compared with direct oral anticoagulants (DOACs). This study aimed to evaluate the effectiveness and safety of concurrent use of rifampin and warfarin versus DOACs, with assessments of outcome-associated factors and oral anticoagulant (OAC) management quality. A total of 142 patients given rifampin plus warfarin (n = 56) or DOACs (n = 86) for over 7 days were included, and their clinical data and outcomes were compared. The median Charlson Comorbidity Index and HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly) score of the two groups were 2 and 3, respectively. The incidence rate of composite ischemic or thromboembolic events was 2.16 and 1.44 per 10,000 patient-days in the warfarin and DOAC groups, respectively, with an adjusted hazard ratio (HR) of 0.41 (95% confidence interval [CI] 0.02-7.34). The incidence rate of composite major bleeding or clinically relevant nonmajor bleeding events was 1.58 and 1.52 per 10,000 patient-days in the warfarin and DOAC groups, respectively, with an adjusted HR of 1.12 (95% CI 0.32-4.45). The risk of composite bleeding events increased with a higher HAS-BLED score (HR: 1.62, 95% CI: 1.02-2.63). Moreover, 34.3% of warfarin users maintained a percent time in therapeutic range of above 50%. Furthermore, 77.9% of DOAC users received appropriate dosing. No significant differences were observed in terms of the incidence of thrombotic or bleeding events between the two groups during coadministration. In addition, a higher HAS-BLED score was associated with a greater risk of bleeding events regardless of the class of OACs used. Finally, close monitoring of bleeding events should be considered.

Platelet Function Testing to Guide Cangrelor Dosing in Patients with Temporary Mechanical Circulatory Support or as a Bridge to Procedure.

Cangrelor is a rapid-acting, intravenous P2Y12 inhibitor that can be used in patients after percutaneous coronary intervention who require mechanical circulatory support or as a bridge to procedure. We retrospectively reviewed adult patients who received platelet function testing (PFT) with the VerifyNow P2Y12 assay while on cangrelor from March 2021 through November 2022. All patients were initiated on 0.75 mcg/kg/min of cangrelor with P2Y12 reaction unit (PRU) values collected 12-24 h after initiation. Cangrelor doses were adjusted per protocol to maintain PRU values of 85-208. A total of 42 patients were included. Thirty-eight patients (90.5%) required temporary mechanical circulatory support while on cangrelor, and 4 patients (9.5%) received cangrelor as a bridge to procedure. The median cangrelor maintenance dose was 0.5 (interquartile range [IQR]: 0.375-0.75) mcg/kg/min, and the median time in therapeutic range with a PRU value between 85 and 208 was 66.6% (IQR: 39.6%-100%). No patients experienced stent thrombosis. A composite major adverse cardiovascular event occurred in 4 patients (9.5%), and major bleeding occurred in 16 patients (38.1%). Compared to empiric cangrelor dosing of 0.75 mcg/kg/min, PFT-guided cangrelor dose adjustment was associated with a median drug cost savings of $1605.60 (IQR: $0-4281.56). Utilizing PFT with cangrelor may allow for lower, individualized dosing while preventing stent thrombosis.

Outcomes of Patients with a Mechanical Heart Valve and Poor Anticoagulation Control on Warfarin.

Patients with a mechanical heart valve (MHV) require oral anticoagulation. Poor anticoagulation control is thought to be associated with adverse outcomes, but data are limited. To assess the risks of clinical outcomes in patients with a MHV and poor anticoagulation control on warfarin. We conducted a retrospective study of consecutive patients undergoing MHV implantation at a tertiary care center (2010-2019). Primary outcome was a composite of ischemic stroke, systemic embolism, or prosthetic valve thrombosis. Major bleeding and death were key secondary outcomes. We constructed multivariable regression models to assess the association between time in therapeutic range (TTR) on warfarin beyond 90 days after surgery with outcomes. We included 671 patients with a MHV (80.6% in aortic, 14.6% in mitral position; mean age 61 years, 30.3% female). Median follow-up was 4.9 years, mean TTR was 62.5% (14.5% TTR <40%, 24.6% TTR 40-60%, and 61.0% TTR >60%). Overall rates of the primary outcome, major bleeding, and death were 0.73, 1.41, and 1.44 per 100 patient-years. Corresponding rates for patients with TTR <40% were 1.31, 2.77, and 3.22 per 100 patient-years. In adjusted analyses, every 10% decrement in TTR was associated with a 31% increase in hazard for the primary outcome (hazard ratio [HR]: 1.31, 95% confidence interval [CI]: 1.13-1.52), 34% increase in major bleeding (HR: 1.34, 95% CI: 1.17-1.52), and 32% increase in death (HR: 1.32, 95% CI: 1.11-1.57). In contemporary patients with a MHV, poor anticoagulation control on warfarin was associated with increased risks of thrombotic events, bleeding, and death.

Living on Oral Anticoagulants: Duke Anticoagulation Satisfaction Scale Results.

Direct oral anticoagulants (DOACs) are widely used in patients with atrial fibrillation and venous thromboembolism. The lack of the need for laboratory monitoring and a better safety than vitamin K antagonists (VKAs) has probably changed the quality of life of patients on these oral anticoagulants. This was a real-life prospective observational cohort study. The aim was to evaluate if a long-term treatment with DOACs could offer a better quality of life than VKAs. Moreover, age, gender, education level, time in therapeutic range for VKAs, taking medication once or twice a day for DOACs, the total daily number of medications and thrombotic and bleeding complications were considered as variables probably associated with the quality of life of these patients. Between January and December 2021, the Duke Anticoagulation Satisfaction Scale (DASS) 25-items was administered as an interview to patients on either VKAs or DOACs therapy. During the follow-up period, all of the patients were closely monitored to evaluate possible bleeding and thrombotic events. The analysis included 300 outpatients treated with VKAs and 254 treated with DOACs. In general, the quality of life was better in patients taking DOACs (DASS total score: DOACs = 44.7, 42.9-46.5 vs. VKAs = 51, 49.2-52.8, p < 0.0001) as the daily-life limitations, hassles and burdens and the psychological impact were less important than in patients on VKAs therapy. VKAs negatively influence the daily-life of the patients in terms of both less satisfaction and time-consuming tasks. DOACs confer a better quality of life even if some concerns emerge from not knowing how their therapy is working.

Clinical value of a tool for managing oral anticoagulation in nonvalvular atrial fibrillation in primary health care. Randomized clinical trial

Introduction and objectivesThe management of atrial fibrillation is complex and requires improvement at strategic points, such as in the control of patients treated with vitamin K antagonists. The aim of this study was to evaluate the impact on health outcomes of a nonvalvular atrial fibrillation decision support tool based on visualization of the time in therapeutic range in primary care. MethodsThe present randomized clinical trial was conducted in 2018 with a 1-year follow-up in 325 primary care centers in Catalonia. In the intervention centers, the decision support tool was installed to control the time in therapeutic range of patients treated with vitamin K antagonists. The tool was not visualized in the control group. ResultsIn total, 44 556 patients were studied. The intervention protected against admission for stroke (adjusted odds ratio [OR], 0.70; 95% confidence interval [95%CI], 0.55-0.88). The number needed to treat was 3502 (95%CI, 3305-3725) while the number of admissions for stroke avoided was 12.63 (95%CI, 11.88-13.38). The intervention also protected against mortality (adjusted OR, 0.78; 95%CI, 0.67-0.90), with a number needed to treat of 13 687 (95%CI, 10 789-18 714) and number of deaths avoided of 3.23 (95%CI, 2.36-4.10). ConclusionsThe decision support tool was associated with slight reductions in the numbers of admissions for ischemic stroke and mortality. Although the follow-up time was short and the effect of the intervention was small, the results are valuable and could improve implementation of the tool.This clinical trial was registered with ClinicalTrials.gov (NCT03367325).

Anti-Xa Assay Monitoring Improves the Precision of Anticoagulation in Venovenous Extracorporeal Membrane Oxygenation.

Unfractionated heparin (UFH) is the most used anticoagulant in patients receiving veno-venous extracorporeal membrane oxygenation (VV-ECMO). Its therapeutic levels are monitored using activated partial thromboplastin time ratio (aPTTr) or antifactor Xa (anti-Xa) assay. This was a retrospective, single-center, cohort study where all adult patients with viral etiology respiratory failure requiring VV-ECMO from January 2, 2015 to January 31, 2022 were included. Anticoagulation was monitored using aPTTr (until November 1, 2019) or anti-Xa assay (after November 1, 2019). We compared the accuracy and precision of anticoagulation monitoring tests using time in therapeutic range (TTR) and variance growth rate (VGR), respectively, and their impact on bleeding and thrombotic events (BTEs). A total of 254 patients, 74 in aPTTr and 180 in anti-Xa monitoring groups, were included with a total of 4,992 ECMO-person days. Accuracy was comparable: mean TTR of 47% in aPTTr and 51% in anti-Xa groups ( p = 0.28). Antifactor Xa monitoring group demonstrated improved precision with a lower variance (median VGR 0.21 vs. 1.61 in aPTTr, p < 0.05). Secondary outcome of less heparin prescription changes (adjusted rate ratio [RR] = 1.01, p = 0.01), fewer blood transfusions (adjusted RR = 0.78, p < 0.05), and ECMO circuit changes (adjusted RR = 0.68, p < 0.05) were seen with anti-Xa monitoring.

Quality of Oral Anticoagulation with Vitamin K Antagonists and Direct Oral Anticoagulants in ‘real-World’ Patients: Lessons from a Five Years Audit Study

Background: Even with the introduction of direct oral anticoagulants (DOACs), anticoagulation clinics (ACs) stand with a key role in monitoring. Indeed, routine evaluation by health care professionals is recommended as it is with vitamin K antagonists (VKA) with adjustments in practices of anticoagulation management services. Quality of oral anticoagulation (QOA) is associated to better clinical outcomes in those patients with indications for such therapy. It is well established that patients receiving VKA therapy, maintenance of an international normalized ratio (INR) in the therapeutic range is essential for treatment efficacy and safety. It has been reported that ACs should aim for a time in therapeutic range (TTR) between 70-80% to optimize benefit and minimize the risk of adverse events. So far, QOA for DOACs is not fully established. Aim: Since few clinical data are available considering the new era of ACs, this study aims to describe actual trends and QOA of an AC at a large academic medical hospital. Methodology: We retrospectively analyzed 23275 appointments of 5 consecutive years (May 2018 to May 2023), corresponding to 930 patients that are regularly followed up at an outpatient AC of a central hospital under anticoagulation for at least 8 weeks. TTR (≥70%) determined by Rosendaal method was used for patients under AVK and for those individuals in DOACs, QOA was considered the presence of therapeutic plasma levels of the drugs after the European Heart Rhythm Association 2021 in, at least, one determination. Patients were divided according to target INR in 3 groups: Group 1 with target INR 2-3, including 809 patients mean age 65±18 years (mean±SD), majority (36.6%) with atrial fibrillation (AF); Group 2 with target INR 2.5-3.5, including 92 patients with mean age 70±11 years, majority (85.9%) with mechanical heart valves; Group 3 with target INR 3-4, including 29 patients with mean age 63±15 years, majority (55.5%) with antiphospholipid syndrome. Seventy patients were under DOACs (apixaban in 74.3%), with mean age of 71±17 years, majority (62.9%) with non-valvular AF, were included in Group 1 and all individuals were under direct inhibitors of factor Xa. Descriptive statistics (mean, standard deviation, minimum, maximum, chi-square), inferential statistics (t-test, A-Nova and effect sizes) tests were performed. Results: The 930 patient population, 52.2% female, mean age of 65±18 years and 87% in Group 1, showed a mortality of 17%. The mean recall interval between appointments was superior to 90 days in 94% of the population. The individuals who died in comparison with the survivors showed higher frequency of AF (54.1%) [ χ 2= 47.099; p&amp;lt;.001; φ=.225], were from Group 1 (93%) [ χ 2= 6.641; p=.036; φ=.085], male (59.2%) [ χ 2= 10.103; p=.001; φ=-.104] and older [76±12 vs .63±18 years (p&amp;lt;.001), respectively]. No differences were noticed in mortality between AVK and DOACs [ χ 2= 1.828; p=.401; φ=-.044], even DOAC patients being older than AVK patients (71±17 vs 65±17; p=.005), respectively. QOA associated with mortality being the individuals who died with higher frequency of no QOA (21.9% vs 13.9%) [ χ 2= 8.126; p=.004; φ=-.101] respectively. The individuals on AVK from Group 1 corresponding to 86% of total population showed a mean TTR of 76%, patients from Group 2 had a TTR of 72% and patients in Group 3 had TTR of 55%. From the individuals under DOACs, only 30% had at least one determination of plasma levels of the drug and all but one showed therapeutic levels. Comparatively with our previous studies related to the periods of 2006-2012 and 2012-2018, we noticed a significant decrease in patient population / appointments size (2087/ 61988) (1587/ 37931),(p &amp;lt;.001) with an increase of TTR in Group 1 (1927/1430 patients) (83% /72%) and Group 2 (120/125 patients) (74% / 69%) but a TTR decrease in Group 3 (40 / 32 patients) (54% / 60%) (p &amp;lt;.001). respectively. Mortality in the 2012- 2018 period was 18%. Conclusions and Discussion: The trends of decreasing the number of anticoagulated patients at our AC with an overall good quality of monitoring but with a low percentage of individuals under DOACs suggests that the majority of anticoagulated population is on these drugs without routine follow up in opposition to the recent recommendations. Our study underlines the importance of the quality of anticoagulation monitoring on mortality that was no different from the previous years before SARS-CoV- 2 pandemic nor between AVK and DOACs.

Impact of Quality and Type of Anticoagulant Treatment, and Inflammatory Biomarkers on Quality of Life and Psychological Morbidity in Patients with Atrial Fibrillation: An Exploratory Study

Background: Owing to increasing worldwide life expectancy, the step rise in the prevalence of atrial fibrillation (AF) represents an urgent public health issue. Indeed, AF can severely affect a patient's quality of life (QoL) since it is associated with serious outcomes, such as stroke, cardiac failure, and cognitive impairment/dementia, resulting in increased morbidity and mortality and a burden for health-care systems. Anticoagulation therapy prevents stroke in individuals with AF, whether with vitamin K antagonists (VKA) or direct oral anticoagulants (DOACs). So far, effective AF management is missing since its etiology is unraveled. Within the research project [Cognitive Decline Risk Profiles and Quality of Life in Atrial Fibrillation: A Longitudinal Study- 2022.072(057-DEFI/058-CE)] a pilot study was conducted to assess a dynamic cohort of AF outpatients who attended the anticoagulation clinic at Santo António University Hospital Center, a Portuguese university public hospital. In this study, QoL, distress and cognitive impairment in patients with AF was assessed considering quality and type of anticoagulant treatment. Methods: With a cross-sectional design, quality of anticoagulation therapy was measured calculating Time in Therapeutic Range (TTR) using Rosendaal method for patients under VKA (TTR&amp;gt;70% as good control); for those patients under DOAC, the presence of plasma therapeutic levels of this drug, taking into account the time of blood sampling, meant an anticoagulant treatment of quality. QoL and distress were assessed by the Atrial Fibrillation Effect on Quality-of-life Questionnaire (AFEQT) and the Depression, Anxiety and Stress Scale (DASS-21), respectively. Cognitive impairment was assessed by the Montreal Cognitive Assessment (MoCA) scale. Data on sociodemographic, clinic [medical history including quality and type of anticoagulation therapy, stroke(CHA2DS2-VASc) and bleeding(HAS-BLED) risk scores, duration of illness) and inflammatory biomarkers were also collected. Results: A total of 62 AF patients were included (mean age 74.4±10.2 years, 59.7% women) with a mean CHA2DS2-VASc of 4.3±1.6 and HAS-BLED of 2.6±1.2. Fifty patients (80.6%) were on VKA and twelve (19.4%) on DOACs (all in apixaban). Those individuals under VKA showed a mean TTR score of 77.1 ± 14.7% (67.4% with a good control) and 11 patients in apixaban presented DOAC therapeutic plasma level. Participants had an illness duration average of 16.02 years±10.62. The mean scores of AFEQT was 2.65 ± .93 showing a good QoL and for MoCA was 21.66 ± 3.90 indicating mild cognitive impairment. Regarding anxiety, depression, and stress (DASS-21) the mean scores were 4.27 ± 4.08, 6.52 ± 4.92 and 7.37 ± 5.37, respectively showing non-clinical psychological morbidity. Patients with higher plasmatic levels of C Reactive Protein (CRP) reported more depression (r= .482; p= .005) and those with a longer illness duration presented a higher level of cognitive impairment, (r= -.398; p= .001). No other associations were found between inflammatory biomarkers and psychological variables. There were significant differences according to sex, age, and illness duration, with women reporting lower QoL (p = .002), higher depression (p = .004), higher stress (p = .005) and older patients (p = .017) as well as patients under VKA and longer disease duration reporting better TTR. (p = .007). No differences were found on patients' QoL (p = .342), anxiety (p = .370), depression (p = .167) and stress (p = .117), cognitive impairment, (p = .084) between good and non-good quality of anticoagulant treatment and between VKA versus DOAC therapy (p = .444). Conclusion: The majority of the patients showed good quality of anticoagulation and QoL, but they revealed mild cognitive impairment. Patients' QoL, distress and cognitive impairment were independent of quality and type of anticoagulation treatment. Older AF patients, particularly those with longer diagnosis, should be assessed for cognitive function on a regular basis, preventing dementia and economic burden. The association of depression with higher levels of CRP in AF patients underlines the nature of these two inflammatory conditions that coexisting associate to worse outcomes. Future studies should assess cognitive function over time to unravel the pathophysiology of cognitive decline and the effect of AF treatments on cognition to optimize and personalize AF therapy.

Comparing follow-up of patients with vitamin K antagonists in a health center: pre- and post- COVID-19 pandemic

Introduction and objectives: During the COVID-19 pandemic, the follow-up of patients treated with vitamin K antagonists (VKAs) may have been affected. This study aims to compare how these patients were monitored preand post-COVID-19 pandemic and understand the impact of non-face-to-face appointments on their follow-up. Methods: We conducted a retrospective cohort study in a Portuguese Health Center. The study included patients treated with VKAs and followed at the Health Center for international normalized ratio (INR) monitoring between March 2019 and March 2021. Data collected: sex, age, type of VKA; INR; date of INR assessment, type of appointment (face-to-face or phone/e-mail). Rosendaal’s method was used to calculate pre-COVID-19 and post-COVID-19 time in therapeutic range (TTR). Good TTR control was defined if values ≥ 70%. Results: 44 patients were included. The mean TTR in the pre-COVID-19 period was 64.55% (95% CI: 58.10 - 71.00%). The post-COVID-19 mean was slightly higher (+ 2.26%), 66.81% (95% CI: 59.66 - 73.97%), but the difference was not statistically significant (p = 0.576). The use of non-face-to-face appointments did not contribute to worsening post-pandemic TTR, showing no lower follow-up than during pre-pandemic period in which all contacts were face-to-face [CI (95%) -0.397 - 0.196 for a reference range -0.489 - 0.693]. Conclusions: The TTR value in both periods was similar and lower than the value defined for effective hypocoagulation. The use of non-face-to-face consultation in the post-COVID-19 period does not seem to have influenced the quality of hypocoagulation.

Evaluating time in therapeutic range in post-acute myocardial infarction patients with left ventricular thrombus treated with vitamin K antagonist

Abstract Background The standard of care for the treatment of post-acute myocardial infarction (AMI) patients with left ventricular (LV) thrombus is oral anticoagulation with vitamin K antagonist (VKA). Due to the narrow therapeutic range of VKA, patients require frequent monitoring. Adequacy of anticoagulation can be assessed by time in therapeutic range (TTR). This study aimed to evaluate the clinical characteristics and outcomes of post-AMI patients with LV thrombus treated with VKA, stratified by anticoagulation adequacy in terms of TTR ≥70% vs. TTR &amp;lt;70%. Methods Among 3000 consecutive echocardiogram results containing the keyword "thrombus" from December 2013 to August 2017, we identified 87 post-AMI patients complicated by LV thrombus and treated with VKA oral anticoagulation. Demographics, treatment including TTR, and outcome measures were analysed. Results The cohort was followed up for a median of 4.3 years (IQR 3.6 – 5.3). Patients with and without adequate anticoagulation had no significant differences in terms of age (p = 0.859), gender (p = 0.438), co-morbidities, LV ejection fraction (p = 0.638). A majority of post-AMI patients with LV thrombus treated with VKA had inadequate anticoagulation, as only 25.3% (n = 22) had TTR ≥70%. SAMe-TT2R2 score, a clinical predictor score for adequacy of anticoagulation, was high in the study cohort (median 4, IQR 3 – 5), with no significant difference between the two groups (p = 0.907). On multivariable analysis, TTR &amp;lt;70% was significantly associated with higher incidence of combined outcomes (presence of bleeding, stroke, or mortality) (HR 2.91 [95% CI 1.01 – 8.39], p = 0.048). Patients with TTR &amp;lt;70% had a higher cumulative incidence of bleeding events while on anticoagulation (p = 0.036), and a higher cumulative incidence of overall stroke on Kaplan-Meier analysis, but did not achieve statistical significance (p = 0.077). Patients with TTR &amp;lt;70% had a significantly higher cumulative incidence of combined outcomes (both while on anticoagulation and overall) compared to those with TTR ≥70% (p = 0.026, p = 0.017). Conclusion LV thrombus patients treated with inadequate VKA anticoagulation of TTR &amp;lt;70% had overall poorer outcomes compared to TTR ≥70%. Further studies are needed to evaluate anticoagulation adequacy in this population.

Quality of anticoagulation and outcomes after mechanical aortic valve replacement in patients with atrial fibrillation: a nationwide cohort study

Abstract Background Mechanical aortic valve replacement (AVR) remains predominant treatment approach for younger patients in need of aortic valve operation. However, little is known about the success of the required Vitamin K Antagonist (VKA) treatment and its relation to adverse events. Purpose We assessed the quality of VKA treatment prior to ischemic events and major bleeding episodes after mechanical AVR in AF patients. Methods The registry-based FinACAF study combining data from several Finnish health care registers covers all patients diagnosed with atrial fibrillation (AF) during 2007–2018 in Finland. In the present study, we included patients undergoing mechanical AVR before or after the AF diagnosis. Hazard ratios (HR) of first-ever ischemic stroke, any bleeding, intracranial bleeding, and myocardial infarction (MI) after AVR were estimated with Fine-Gray model adjusted for known bleeding and stroke risk factors. Results We identified 1086 patients (27.1% female, median age 62.8 (IQR 56.2–68.3) years) with mechanical AVR and AF diagnosis, either before (58.8%) or after (41.2%) the operation, and without prior bleeding episode, ischemic stroke, or MI. Cumulative incidence estimates at 10 years after AVR were 12.8% for ischemic stroke, 27.9% for significant bleeding, 5.8% for intracranial hemorrhage (ICH), and 7.2% for MI. International Normalized Ratio (INR) was &amp;lt;2.0 during 27.9–33.9% of ischemic events and lower mean Time in Therapeutic Range (TTR) with INR target ≥2.0 was associated with subsequent higher stroke occurrence (standardized adjusted HR 1.23 (1.03–1.49) for lower TTR, p=0.030, Figure 1). INR was &amp;gt;3.5 during 23.4–24.3% of major bleeding events and lower mean TTR (INR target 2.0–3.5) was associated with subsequent bleeding episode (adjusted HR 1.20 (1.03–1.41), p=0.021, Figure 2). Mortality was high (10-year estimated survival 71.1%), and lower mean TTR (INR target 2.0–3.5) was associated with higher mortality (adjusted HR 1.56 (1.39–1.72), p&amp;lt;0.001). Conclusions Adverse events after mechanical AVR are frequent in AF patients and mortality is high. Suboptimal mean TTR appears to identify the patients at high risk for both bleeding episodes and ischemic stroke.Figure 1.Figure 2.

Short versus long-term anticoagulation for left ventricular thrombosis resolution during vitamin k antagonist therapy

Abstract Background The optimal duration of anticoagulant therapy to achieve thrombus resolution and prevent cardioembolic events in left ventricular thrombosis (LVT) has not yet been established. Purpose The purpose of our study is to evaluate the incidence of LVT resolution at 3 versus 12 months of vitamin K antagonists (VKAs) therapy. Methods Consecutive patients diagnosed with LVT and treated with VKAs for at least 12 months at 5 anticoagulant outpatient clinics in Italy were retrospectively included. The primary effectiveness outcome was on-treatment thrombus resolution while the secondary was objectively documented on-treatment acute ischemic stroke, peripheral embolism, and myocardial infarction at 12-months follow-up. Safety outcomes were on-treatment major and clinically relevant non-major bleedings at 12-months follow-up as defined by the ISTH criteria. Cumulative incidences of thrombus resolution with 95% confidence intervals (CIs) were calculated while other outcomes were descriptively reported. Multivariable Cox hazards models were calculated using age, sex, reduced left ventricular ejection fraction (EF &amp;lt; 35%), VKAs monotherapy, and time in therapeutic range (TTR) below 60% as covariates for thrombus persistence at 12-months of follow-up. Results Out of 95 patients, 87 were finally included (Table) and 8 excluded due to the lack of relevant data. Median age was 67 years and 75.9% were men. A total of 64.4% of patients had acute myocardial infarction as risk factor for LVT development while 21.8% and 5.7% of patients had dilated and primary hypertrophic cardiomyopathy, respectively. A reduced EF and atrial fibrillation were present in 77.0% and 19.5% of patients, respectively. All but one patient received warfarin with a median TTR of 54%, and 35.5% of patients did not receive concomitant antiplatelet therapy. All included patients received VKAs for at least 12-months. The 3 and 12 month cumulative incidences (Figure) of thrombus resolution were 34.5% (95% CI, 24.7%-44.5%) and 68.3% (95% CI, 57.2%-77.1%), respectively. At multivariable Cox regression analysis, the presence of a reduced EF appeared to be associated with a higher risk of thrombus persistence at 12-months follow-up (Hazard Ratio 3.09; 95% CI 1.27-7.55; p=0.013). During 12-months follow-up, two patients (2.3%) had acute ischemic stroke at 4 and 7 months from the start of VKAs therapy. Three patients (3.4%) had a major and 5 (5.7%) a clinically relevant non-major bleeding that occurred within the first three months of VKAs. Conclusions A 12-month course of anticoagulant therapy with VKA appeared to be effective and safe in patients with LVT and appeared to be associated with a higher cumulative incidence of LVT resolution than a 3-month course. A reduced left ventricular EF was associated with a higher risk of LVT persistence. Whether anticoagulant agents with improved ease-of-use and safety profile are effective in this setting remains undefined.Baseline patients' characteristicsCumulative incidences of LVT resolution

Patients with AF and dementia are undertreated for their AF and cardiovascular comorbidities: results from the GARFIELD-AF registry

Abstract Background Oral anticoagulation (OAC) is key in preventing stroke in patients with atrial fibrillation (AF). However, patients with AF and dementia pose practical therapeutic challenges, such as compliance and haemorrhagic complications, resulting in possible underuse of cardiovascular (CV) treatment. Purpose The aim of this study is two-fold: a) to determine whether AF patients with dementia are undertreated for stroke prevention with OAC and for their CV comorbidities and b) to assess the risks and benefits of OAC in AF patients with dementia. Methods Analyses were conducted in newly diagnosed AF patients enrolled in GARFIELD-AF, the largest multinational prospective AF registry. Medical history of dementia was recorded at enrolment. Guideline-directed medical therapy (GDMT), defined according to ESC guidelines, was explored for coronary artery disease (CAD), diabetes, heart failure (HF), hypertension, and peripheral vascular disease (PVD). Propensity score weighting was applied to obtain estimates of OAC effect on all-cause mortality and stroke within two-year follow-up. Major bleeding occurrence is simply reported due to the low number of events. Results The study comprised 764 (1.5%) AF patients with dementia and 50,966 (98.5%) without dementia. Patients with dementia were more often female (58% vs 44%), older (median age 82 vs 71) and had higher prevalence of comorbidities, resulting in higher CHA2DS2-VASc (excl. sex; median 5.0 vs 3.0) and HAS-BLED score (median 2.0 vs 1.0) compared to patients without dementia. The proportion anticoagulated was lower among those with dementia (60% vs 70%), with fewer patients receiving VKA (27% vs 42%) (Fig. 1). Despite the increase in NOAC use among patients with dementia (17% in 2010-2013 vs 48% in 2015-2016), 35% remained non-anticoagulated in 2015-2016. Appropriate GDMT was lower among patients with dementia for the five considered comorbidities combined (35% vs 45%), with substantial differences observed for HF (35% vs 50%), CAD (27% vs 39%) and PVD (36% vs 48%) compared to patients without dementia. In patients with dementia, OAC usage was associated with lower all-cause mortality (HR 0.69; 95% CI 0.48-1.00). In contrast to patients without dementia, no evidence of a stroke risk reduction with OAC was observed among patients with dementia (HR 1.10; 95% CI 0.50-2.43) (Fig. 2). This finding might be explained by the higher proportion of patients with dementia receiving a reduced NOAC dose (73% vs 39% of NOAC receivers) and their lower VKA quality control (37% vs 46%, defined as time in therapeutic range &amp;gt;65%). Seven (1.6%) and eight (2.7%) major bleeding events occurred among patients with dementia who were on or not on OAC, respectively. Conclusions Despite their high risk of stroke, patients with AF and dementia are often undertreated for their AF and CV comorbidities. Our results support the use of OAC and should help inform treatment decisions in this vulnerable population.

Risk factors for serious adverse events related to vitamin K antagonists in children with congenital or acquired heart disease: a prospective cohort study

ObjectivesTo assess the occurrence of thrombosis and major bleeding in children with congenital or acquired heart disease (CAHD) treated with VKA and to identify risk factors for these serious adverse events (SAE). Study designAll children enrolled in our VKA dedicated educational program between 2008 and 2022 were prospectively included. The time in therapeutic range (TTR) was calculated to evaluate the stability of anticoagulation. Statistical analysis included Cox proportional hazard models. ResultsWe included 405 patients. Median follow-up was 18.7 (9.3–49.4) months. The median TTR was 83.1 % (74.4 %–95.3 %). No deaths occurred because of bleeding or thrombotic events. The incidences of thrombotic and major bleeding events were 0.9 % (CI95 % [0.1–1.8]) and 2.3 % (CI95 % [0.9–3.8]) per patient year, respectively. At 1 and 5 years, 98.3 % (CI95 % [96.2 %–99.2 %]) and 88.7 % (CI95 % [81.9 % 93.1 %]) of patients were free of any SAE, respectively. Although the mechanical mitral valve (MMV) was associated to major bleeding events (HR = 3.1 CI95 % [1.2–8.2], p = 0.02) in univariate analysis, only recurrent minor bleeding events (HR = 4.3 CI95 % [1.6–11.7], p < 0.01) and global TTR under 70 % (HR = 4.7 CI95 % [1.5–15.1], p < 0.01) were independent risk factors in multivariable analysis. In multivariable analysis, giant coronary aneurysms after Kawasaki disease (HR = 7.8 [1.9–32.0], p = 0.005) was the only risk factor for thrombotic events. ConclusionOverall, VKA therapy appears to be safe in children with CAHD. Suboptimal TTR, regardless of the indication for VKA initiation, was associated with bleeding events.

Abstract 15632: Warfarin Dose Management Using Offline Deep Reinforcement Learning

Introduction: Warfarin is a commonly prescribed anticoagulant for treating atrial fibrillation, mechanical valves, and venous thromboembolism. Warfarin dose management remains challenging due to dosing variability between patients and warfarin’s narrow therapeutic window. Time in therapeutic range (TTR) is critical to warfarin’s safety and efficacy, but TTR typically remains low (40-50%) in community practices. Specialized anticoagulation clinics and protocolized approaches can increase TTR but have great administrative burdens and health care costs. Aim: To develop standardized optimal warfarin dose decision support using a machine learning model based on time series anticoagulation data and patient demographic characteristics Methods: The dataset included 12,497 warfarin patients monitored in the anticoagulation tracker of electronic medical records across the Mayo Clinic Enterprise. The dataset contained time series anticoagulation data (warfarin dose, INR, INR target range) and patient demographic characteristics. We implemented an offline deep reinforcement learning model (DRL) to predict the cumulative warfarin dose for the days until the next INR test based on a patient’s historical anticoagulation data. Prior approaches utilized traditional supervised learning methods such as regression or Long Short Term Memory (LSTM) neural networks to approximate a function mimicking the behavior of the training data. On the other hand, DRL learned an optimal dosing policy through continuous interaction and feedback from the training data. The key advantage of DRL is the model can learn to behave differently (and potentially better) for suboptimal clinical states in the data such as overdosing or underdosing. To evaluate the DRL model we compared the predicted warfarin doses with the physician-prescribed doses Results: DRL model’s prediction accuracy was 96.96%, outperforming our implementation of a baseline LSTM model with a prediction accuracy of 70.58%. Further evaluation of the DRL model indicated that the model correctly adjusted the warfarin dose at time steps when patients had out-of-range INRs. Conclusions: Offline deep reinforcement learning demonstrates potential in supporting warfarin dose management to maximize TTR.

Abstract 14451: Switching From Warfarin to Direct Oral Anticoagulants (DOACs) in Medicine Clinic at a Safety Net Hospital in New York City: A Quality Improvement Project

Introduction: Many patients are still using warfarin for thromboembolic prevention, even though Direct-Acting Oral Anticoagulants (DOACs) have replaced it in most indications to decrease the need for frequent dose adjustments and minimize drug interactions. Methods: This study is a clinic patient-based observational quality improvement project to review warfarin use in adult patients following at the anticoagulation clinic at Metropolitan Hospital. Electronic medical records were screened, and TTR was calculated over 3 months. STATA was used for statistical analysis, including Histograms, Skewness-Kurtosis tests for normality, student-T tests for continuous variables, and χ2 tests for categorical variables. The P-value of less than 0.05 was considered statically significant. Results: A total of 45 patients were included; the mean age was 61, of whom 23 (51.1%) were males. The comorbidities observed were hypertension (HTN), diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), and obesity. The time in therapeutic range (TTR) was less than 65% in 22 patients (48.9%). Warfarin was indicated in 28 patients (62.2%) and not indicated in 17 patients (37.8%), out of which 6 patients (36.3%) agreed to switch to direct oral anticoagulants (DOACs) (Figure 1). Conclusions: Our project revealed a significant number of patients are still using warfarin despite being suitable for DOACs. 60% prefer warfarin due to perceived safety with frequent clinic visits. Socioeconomic status affects the transition. The PINNACLE Study identified practice and provider variations, Practices with high-volume clinics, more electrophysiologists, and those located in the western region are more likely to switch to DOACs. Based on our findings, we recommend the following: - Physicians should engage in shared decision-making with patients on warfarin use. - Physicians may need to discuss the available DOACs options with insurance companies due to coverage limitations.

Abstract 12981: Digital Health for the Management of Oral Anticoagulation Therapy: A Systematic Review and Meta-Analysis

Background: Direct oral anticoagulants (DOACs) have progressively replaced vitamin K antagonists (VKAs). However, in certain conditions, especially antiphospholipid syndrome, mechanical heart valves and rheumatic mitral stenosis, VKAs remain the only drugs with established safety and efficacy. In low-income contexts, they are frequently the preferred option due to the high costs of DOACs. Its management is often challenging, and different digital health strategies have been implemented to support it. Aims: To systematically review the evidence on the impact of digital health strategies to support anticoagulation management compared to usual care on thromboembolic and bleeding events. Methods: Randomized controlled trials were searched in 5 databases from inception to September 2021. Two independent reviewers performed study selection, data extraction, and quality assessment using the Cochrane risk of bias tool (RoB2). Total thromboembolic events, major bleeding, mortality, and time in therapeutic range were assessed. Results were pooled using random effect models. Results: In total, 25 randomized controlled trials were included (25,746 patients) and classified as moderate to high risk of bias. Telemedicine resulted in a trend of reduced risk of thromboembolic events (13 studies, relative risk [RR] 0.75, 95% CI 0.53-1.07; I2=42%), comparable rates of major bleeding (11 studies, RR 0.94, 95% CI 0.82-1.07; I2=0%) and mortality (12 studies, RR 0.96, 95% CI 0.78-1.20; I2=11%), and an improved time in therapeutic range (16 studies, mean difference 3.38, 95% CI 1.12-5.65; I2=90%). In the subgroup of multitasking intervention, telemedicine resulted in an important reduction of thromboembolic events (RR 0.20, 95% CI 0.08-0.48). Conclusions: Digital health strategies resulted in similar rates of major bleeding and mortality, a trend for fewer thromboembolic events and better anticoagulation quality compared to standard care. Given the potential benefits of digital health-based care, such as greater access to remote populations, these findings may encourage further implementation of these strategies for anticoagulation management, particularly as part of multifaceted interventions for integrated care of chronic diseases.

Antiphospholipid Antibody Syndrome (APS) Pediatric Patient Outcomes on Warfarin

Background: Antiphospholipid antibody syndrome (APS) is an acquired thromboembolism (TE) risk factor and places patients at very high risk of recurrent TE. APS diagnosis requires venous (deep vein thrombosis (DVT) or pulmonary embolism (PE)) or arterial thromboembolism and laboratory diagnosis including persistently positive lupus anticoagulant (LA) or elevated anticardiolipin (aCL) and/or beta 2 glycoprotein I (B2GPI) antibodies tested 12 weeks apart. Vitamin K antagonist (warfarin) is the standard of care anticoagulant to reduce risk of TE recurrence in APS patients. Warfarin is dosed based on the International Normalized Ratio (INR) with established therapeutic ranges for optimal efficacy and safety. The reported time in therapeutic range (TTR) varies greatly across specialties with an average TTR of 50-55%. However, it is often difficult to maintain target INR in APS. Furthermore, there is limited data evaluating pediatric patients with APS and their TTR on warfarin and outcomes. Aim: To evaluate the relationship of APS status to TTR and outcomes of patients &amp;lt; 21 years of age with APS who are on warfarin anticoagulation. Methods: This was a single center analysis of APS patients between July 2019 and May 2022 who were enrolled in a multi-center prospective study of pediatric patients on warfarin therapy, eKITE (electronic KidClot Thrombophilia Education). The study included an online learning series regarding warfarin management. Home INR meters and test strips were provided to all patients to perform INR testing. INR values were reported by patients and recorded. Demographic and clinical data was extracted from the electronic medical record, target INR was set by the treating provider, and TTR was calculated as a surrogate for safe, effective warfarin management. Results: Nine patients (n=9) with APS were identified for this analysis, mean age 16.7 years (range 12-19 years). Demographic and laboratory findings are summarized in Table 1. Most patients had secondary APS due to systemic lupus erythematous (SLE) 78% (n=7) and 22% (n=2) had other primary diagnoses. APS antibody status included single positive in 67% (n=6), double positive in 22% (n=2), and triple positive in 11% (n=1). More specifically, APS criteria were met by persistently elevated LA in 78% (n=7), aCL IgM in 22% (n=2) with overall mean aCL IgM of 34.4 MPL^ (range 9.9-127.9), B2GPI IgG in 11% (n=1) with overall mean B2GPI IgG SGU* of 13.1 (range 0.9-63.3), and B2GPI IgM in 22% (n=2) with overall B2GPI IgM mean of 32.5 SGU (range 3.3-190.9). At time of presentation 67% (n=6) of patients had DVT, 44% (n=4) had PE, 11% (n=1) had arterial TE, and 22% (n=2) presented with DVT &amp; PE. Mean TTR for all patients was 56%. TTR for single positive APS was 66%, double positive APS 39%, and triple positive APS 33%. TTR for secondary APS (SLE) and non-SLE diagnoses was 53% and 68% respectively. Mean dose changes were 11 (range 0-48) with one single positive LA patient requiring 48 dose changes, and two patients with single positive LA not requiring any dose changes. Two patients (22%) developed recurrent clot. One triple positive APS patient developed two DVTs and one non-SLE patient developed recurrent arterial TE. Three patients (33%) had minor bleeding events including mild epistaxis and hematemesis not requiring intervention. One patient (11%) had a major bleeding event, hemoperitoneum from pseudoaneurysm extravasation, while resuming warfarin during post-operative period, and required takeback surgery with sub-therapeutic INR 1.5 at the time of event. Conclusion: The mean TTR for pediatric patients with APS is similar to what is reported in other populations despite the challenge of managing warfarin in this group where the INR may be affected by primary disease modifying medications or disease flares. The risk of recurrent TE remains high in APS patients. Home INR monitors are a safe and effective strategy in managing warfarin anticoagulation in APS patients, reducing time and laboratory monitoring burden for frequent dose changes, which ultimately improves quality of life.Optimizing TTR is important to decrease risk of recurrent TE or bleeding in these high risk APS patients.

Apixaban Vs Vitamin K Antagonist As Anticoagulant Therapy in Patients with End-Stage Kidney Disease on Hemodialysis and with Atrial Fibrillation

BACKGROUND Evidence of net safety and benefit of anticoagulation for stroke prevention in patients with end-stage kidney disease (ESKD) on hemodialysis and with atrial fibrillation (AF) is lacking because patients with advanced CKD and those with end-stage kidney disease (ESKD) have been excluded from randomized clinical trials of stroke prevention in AF. In Europe, apixaban is not approved for the indication of prevention of stroke and systemic embolism in adult patients with ESKD on hemodialysis and AF. AIM To assess the effectiveness and safety according to Apixaban or VKA treatment. The effectiveness outcome was defined by ischemic stroke, all-cause death and myocardial infarction. The safety outcome was defined by a first event of major bleeding, clinically relevant nonmajor bleeding, or all-cause death. METHODS Unicenter, observational and retrospective study. Data was collected between January 2018 and July 2022. We included adult patients with ESKD on hemodialysis and AF and a CHA2DS2-VASc score ≥2 treated with low dose of Apixaban (2.5 mg twice daily) or VKA from the beginning of treatment. Patients in the VKA group received Acenocoumarol. Demographic, laboratory data and clinical presentation of AF were collected. Patients had a minimum follow-up (FU) of 6 months. Apixaban plasma drug concentrations were measured during the FU (week 1 and month 3). Blood samples were draw just before the next dose (Ctrough) and at 2-3 hours (Cpeak) after of drug intake using the Technoclone anti-Xa assay from Technoclone (Vienna-Austria). Bleeding events were classified according to ISTH criteria. RESULTS A total of 302 patients with NVAF and ESKD on hemodialysis were included. Among all patients, 192 (63.5%) were treated with Apixaban and 110 VKA. Mean FU was 14.8 and 12.5 months (DOAC vs VKA; p:0.53). Demographic characteristics are summarised in table 1. In Apixaban group, 100% of patients received reduce-dose, according to the care protocol established in our center and showed predictable pharmacokinetic, Ctrough (94.5- 180 μg/L) and Cmax (150-419 μg/L). In VKA group, Time in therapeutic range (international normalized ratio, 2.0-3.0) for Acenocumarol treated patients was 42% (interquartile range, 19%-60%). Stroke or systemic embolism occurred in three patients in the Apixaban group (1.04 %/year) and seven patients in the VKA group (7.2 %/year) [DOAC vs LMWH; p&amp;lt;0.05]. The apixaban group experienced fewer overall bleeding events than the VKA group (17.3% vs 39.7%; P = .01); this significant difference persisted in adjusted analysis (OR = 0.13; 95% CI = 0.04-0.42; P = .001). Major bleeding events were less frequent in the apixaban group compared with patients on VKA (4.7% vs 25%; P = .01). There were no significant differences regarding in all-cause mortality, 18.8% versus 21.5% respectively. CONCLUSIONS Compared to VKA, our findings suggest that low dose of apixaban is a safe and effective alternative in patients with AF and ESKD on hemodialysisis and low dose of apixaban showed predictable pharmacokinetic.