Mean Time In Therapeutic Range Research Articles

A nurse-led atrial fibrillation clinic: Impact on anticoagulation therapy and clinical outcomes.

Nurses play a central role in the management of atrial fibrillation (AF) patients. An unresolved question is whether a nurse-led clinic would improve clinical outcomes. Herein, we investigated the impact of a nurse-led clinic on anticoagulation therapy and clinical outcomes in a cohort of naïve AF patients. Prospective study including AF patients starting vitamin K antagonists (VKAs) into a nurse-led AF clinic. These patients were followed in this specific AF clinic. Additionally, AF patients already taking VKAs for 6months followed according to the routine clinical practice were included as comparison group. The quality of anticoagulation was assessed at 6months. Efficacy and safety endpoints were recorded during follow-up. We included 223 patients (Nurse-led clinic: 107; Usual care: 116). The mean time in therapeutic range and the proportion of INRs within the therapeutic range were similar in both groups. During 2.06 (IQR 1.01-2.94) years of follow-up, 64 (28.7%) patients changed to direct-acting oral anticoagulants. The proportion of switchers was higher in the nurse-led clinic (37.4%) than in the usual care group (20.7%) (P=.006) and these patients spent less time to switch (2.0 [IQR 0.7-2.9] vs 6.0 [IQR 3.7-11.2] years; P<.001). Importantly, the annual rate of ischaemic stroke/TIA was significantly lower in the nurse-led clinic (0.47%/year vs 3.88%/year, P=.016), without differences in safety endpoints. A nurse-led AF clinic may offer a "patient-centered" review and holistic follow-up, and it would be associated with a reduction of ischaemic stroke/TIA, without increasing bleeding complications. Further studies should confirm these results.

Warfarin control in Hong Kong clinical practice: a single-centre observational study

Time in therapeutic range (TTR) assesses the safety and effectiveness of warfarin therapy using the international normalised ratio. This study investigated the TTR in Hong Kong patients using both European and Japanese therapeutic ranges and patients' economic and clinical outcomes. Predictors of poor warfarin control and patient knowledge concerning warfarin therapy were assessed. A 5-month observational study with retrospective and prospective components was conducted in the Prince of Wales Hospital. The study examined electronic patient records of patients who received warfarin for at least 1 year during the period from January 2010 to August 2015. Patient knowledge was assessed via phone interview using the Oral Anticoagulation Knowledge (OAK) test. In total, 259 patients were included; 174 completed the OAK test. The calculated mean TTR was 40.2±17.1% (European therapeutic range), compared with 49.1±16.1% (Japanese therapeutic range) [P<0.001]. Mean TTR was higher in patients with atrial fibrillation than in patients with prosthetic heart valve (P<0.001). The abilities of TTR to predict clinical and economic outcomes were comparable between European and Japanese therapeutic ranges. Patients with ideal TTR had fewer clinical complications and lower healthcare costs. Patients with younger age exhibited worse TTR, as did those with concurrent use of furosemide, famotidine, or simvastatin. Mean OAK test score was 54.1%. Only 24 (13.8%) patients achieved a satisfactory overall score of ≥75% in the test. Warfarin use in Hong Kong patients was poorly controlled, regardless of indication. Patient knowledge concerning warfarin use was suboptimal; thus, additional patient education is warranted regarding warfarin.

Quality of oral anticoagulation control in Chinese patients with non-valvular atrial fibrillation: a prospective controlled study

Objective The sex, age, medical history, treatment, tobacco use, race risk (SAMe-TT2R2) Score; the sex, age, medical history, treatment, tobacco use, genotype combination (SAMe-TT2G2) Score; and the so-called modified SAMe-TT2R2 scores have been proposed to predict the anticoagulation quality for patients with non-valvular atrial fibrillation (NVAF). The data from a prospective controlled study is used to validate the SAMe-TT2R2 and SAMe-TT2G2 scores in Chinese NVAF patients treated with warfarin and to evaluate the association of factors with time in therapeutic range (TTR) to predict the quality of oral anticoagulation control. Methods A total of 379 patients with NVAF under warfarin treatment for a three-month follow-up were included in this prospective, multicenter study. The quality of oral anticoagulation control was evaluated by the TTR. The TTR was dichotomized for binary logistic regression analysis, using a cutoff point for classification as an inadequate (TTR < 65.0%) control. Results The 379 NVAF patients had a mean TTR of 58.35 ± 26.33% and median SAMe-TT2R2 and SAMe-TT2G2 scores of 3 and 2, respectively. The discrimination performances of the SAMe-TT2R2 and SAMe-TT2G2 scores for inadequate anticoagulation control (TTR < 65.0%) were poor (c-index < 0.60). The gene frequency of CYP2C9*3 was 3.2% and that of VKORC1-1639 G > A was 89.3%. Genetic variation of CYP2C9*3 and VKORC1-1639 G > A did not affect TTR after initial treatment. The condition TTR < 65.0% was associated with an age below 60 without genotype-guided warfarin dose initiation and concomitant torasemide. Conclusions A warfarin-dosing algorithm used for initial treatment of patients older than 60 helps to achieve a better quality of oral anticoagulation control, whereas concomitant torasemide can produce a negative effect. These findings provide useful information for future investigations on the quality of oral anticoagulation control in Chinese anticoagulation clinical practice.

Effect of SAMe-TT2R2 score and genetic polymorphism on the quality of anticoagulation control in Qatari patients treated with warfarin

There is no strong evidence on pharmacogenetics role on the quality of INR control after the initiation phase and on the maintenance of stable INR on the long term as measured by the time in therapeutic range (TTR). The benefit of a score such as SAMe-TT2R2 is that it can preemptively guide clinicians on whether to start the patient on warfarin or direct oral anticoagulant. To determine the association between genetic variants in CYP2C9, VKORC1, and CYP4F2 and TTR. To validate SAMe-TT2R2 score predictive ability on the quality of anticoagulation in Qatari patients. This is an observational nested case–control study that was conducted on a cohort of Qatari patients treated with warfarin with previously identified genotype for the CYP2C9, VKORC1, and CYP2F4. The sample size of this cohort was 148 patients. Mean TTR was 62.7 ± 21%. TTR was not significantly different among carriers of the CYP2C9*2 &*3, VKORC1(–1639G>A) or CYP4F2*3 compared to their non-carriers alleles. None of the factors in the SAMe-TT2R2 score had a significant effect on the TTR except for the female gender where TTR was significantly lower in females (n = 89) compared to males (n = 59) (59.6 ± 21% vs. 67.2 ± 20%, p = 0.03). Furthermore, patients with SAMe-TT2R2 score of zero had significantly better TTR compared to those with higher scores (76.5 ± 17% vs. 61.8 ± 21%, p = 0.04). Logistic regression analysis showed that high SAMe-TT2R2 score was the only statistically significant predicting factor of poor INR control (odds ratio (OR) 5.7, 95% confidence interval (CI) 1.1–28.3, p = 0.034). Genetic variants have no contribution to the quality of INR control. SAMe-TT2R2 score was predictive for the poor quality of anticoagulation in a cohort of Qatari patients.

Comparing therapy outcomes of patients before and after enrolling in an anticoagulation self‐testing program

AbstractPurposePatients managed by the Froedtert &amp; the Medical College of Wisconsin (F&amp;MCW) Anticoagulation Clinics (ACC) have three monitoring options: face‐to‐face management, telephone management, or self‐testing management with limited clinician interaction only when International Normalized Ratios (INRs) are out of range or when clinically appropriate. To investigate if F&amp;MCW ACC's current method of less frequent interaction for self‐testing is safe and effective, the purpose of this study was to determine if patients taking warfarin who were previously managed either face‐to‐face or via telephone call in the F&amp;MCW ACC can be as effectively managed while self‐testing at home.MethodsThis pre‐post study analyzed data from face‐to‐face or telephone call anticoagulation management 6 months before and after each patient's self‐testing teach‐visit date. The primary outcome was the patients' time in therapeutic range (TTR) for INR values before and after enrolling in the self‐testing program. Secondary outcomes were the number of major bleeding and thromboembolic events and the number of INRs greater than 5.0 before and after transitioning to INR self‐testing. Patients served as their own control group for all outcomes of this study.ResultsThe mean (standard deviation [SD]) TTR for subjects 6 months before and after transitioning to self‐testing was 69.9% (20.9) and 73.2% (18.0), respectively, demonstrating a statistically significant increase in TTR of 3.3% (25.4) with self‐testing (P = .047). Thirty‐six critical values occurred in the 6 months before self‐testing and 24 occurred in the 6 months after transitioning to self‐testing (P = .23). Additionally, four major bleeding and thromboembolic events occurred in four different patients in the 6 months after transitioning to self‐testing (P = .13).ConclusionsF&amp;MCW ACC's model for self‐testing management of every 2‐week self‐tests and limited clinician interaction demonstrates statistically significant improvements in TTR after patients transitioned to self‐testing. There was no statistically significant increase in adverse events following this transition.

Effect of CYP3A Genetic Variants on Different Measures of Tacrolimus Variability in Heart Transplant Recipients

CYP3A genetic variants are associated with tacrolimus (TAC) dose requirements and levels. However, the contribution of CYP3A genetics to variability in TAC levels is unclear. We sought to determine the relationship between CYP3A genetic variants and three measures of TAC variability, i.e., coefficient of variation (CV) of dose-adjusted trough levels (C0/D), time in therapeutic range (TTR), and TTR via the Rosendaal method (Rosendaal TTR), in adult heart transplant (HTx) recipients. This was a retrospective study of 69 HTx recipients during the first-year post-HTx. Patients were grouped as CYP3A5 expressors (CYP3A5*1/*1 or *1/*3) or non-expressors (CYP3A5*3/*3) and CYP3A4 non-carriers (CYP3A4*1/*1) or carriers (CYP3A4*1/*22 or *22/*22). Combined CYP3A phenotypes included extensive (EM, CYP3A5*1 carrier + CYP3A4*1/*1) vs intermediate (IM, CYP3A5*3/*3 + CYP3A4*1/*1) vs poor (PM, CYP3A5*3/*3 + CYP3A4*22 carrier) metabolizers. TAC data were extracted from medical records. The primary outcome was TTR. Secondary outcomes were CV of C0/D and Rosendaal TTR. Data were analyzed using generalized linear models. The study consisted of 80% men and 78% Caucasians (mean age at HTx=50 ± 13 years). Mean TTR, CV, and Rosendaal TTR were 30.9 ± 13.6%, 42.5 ± 21.0%, and 37.4 ± 19.8%, respectively. TAC-CYP3A variability data are shown in the table. TAC TTR was significantly lower in CYP3A5 expressors vs non-expressors, 24.0% (95% CI=18.0 to 30.1) vs 33.3% (95% CI=29.7 to 37.0), p=0.010. Similar findings were observed for combined CYP3A phenotype, with differences largely driven by CYP3A5 genotype. Neither CYP3A5 nor CYP3A4 genetics were significantly associated with CV or Rosendaal TTR. Of the three measures of variability evaluated in our cohort, CYP3A5 genetics was only associated with TAC TTR. These findings suggest that different measures of TAC variability may elicit different findings in pharmacogenomic association studies of HTx recipients.

The SAMe-TT2R2 score as an indicator of warfarin control for patients with deep vein thrombosis in Queensland, Australia.

Oral anticoagulation options for patients with venous thromboembolism (VTE) include vitamin K antagonists like warfarin. Good warfarin control is linked to outcomes of therapy, and the SAMe-TT2R2 model has been reported to predict control in atrial fibrillation patients with scores ≥ 2 linked to poor control. There has been limited and conflicting data in VTE populations, therefore this study aimed at determining the predictive ability of this model in Australian patients with deep vein thrombosis. Retrospective data of patients receiving warfarin care at a private pathology clinic in Queensland was collected. The time in therapeutic range (TTR) and SAMe-TT2R2 score was calculated for individual patients. Mean TTR and patients with TTR ≥ 65% were used for analysis and comparison across patients categorised as a score of 0-1 and ≥ 2. Of the 533 patients, the majority had a SAMe-TT2R2 score of 0-1. No significant difference was found in mean TTR between patients with a score of 0-1 and ≥ 2 but there was a significantly higher percentage of patients with a TTR ≥ 65% between groups (93.8% vs. 69.2%, p < 0.0001, respectively). The SAMe-TT2R2 score may assist in identifying patients with VTE likely to achieve good control (TTR ≥ 65%), but further investigation is required to determine the most suitable model for predicting warfarin control in this population.

Anticoagulation Therapy in Patients with Non-valvular Atrial Fibrillation in a Private Setting in Brazil: A Real-World Study.

ResumoFundamento:A segurança e a eficácia da varfarina dependem da qualidade do controle da anticoagulação. Estudos observacionais associam controle deficiente com aumento de morbidade, mortalidade e custos com saúde.Objetivos:Desenvolver um perfil de pacientes com fibrilação atrial não valvar (FANV) tratados com varfarina em ambiente ambulatorial e hospitalar privado brasileiro, avaliar a qualidade do controle da anticoagulação e sua associação com resultados clínicos e econômicos.Métodos:Este estudo retrospectivo, por meio de um conjunto de dados de seguros privados de saúde no Brasil, identificou pacientes com FANV tratados com varfarina entre 01 de maio de 2014 a 30 de abril de 2016, descreveu seu manejo da anticoagulação e quantificou os custos relacionados à doença. Foram recuperados dados demográficos, histórico clínico, medicação concomitante e tempo na faixa terapêutica (TTR) dos valores da razão normalizada internacional (RNI). Os pacientes foram agrupados em quartis de TTR, com um bom controle sendo definido como TTR ≥65% (método de Rosendaal). Sangramentos maiores e custos médicos diretos por todas as causas foram calculados e comparados entre subgrupos de controle bons e ruins. Valores de p < 0,05 foram considerados estatisticamente significantes.Resultados:A análise incluiu 1220 pacientes (mediana de seguimento: 1,5 anos; IIQ: 0,5–2,0). Em média, cada paciente recebeu 0,95 medidas mensais de RNI (RNI média: 2,60 ± 0,88, com 26,1% dos valores < 2 e 24,8% > 3), (mediana de TTR: 58%; IIQ: 47-68%), (TTR médio: 56,6% ± 18,9%). Apenas 31% dos pacientes estavam bem controlados (TTR médio: 78% ± 10%), com 1,6% apresentando grandes sangramentos na mediana do seguimento e custos médicos diretos por membro por ano (PMPY) de R$25.352 (± R$37.762). Pacientes com controle abaixo do ideal (69%) foram associados a 3,3 vezes mais sangramentos graves (5,3% vs. 1,6%; p <0,01) e custos 40% maiores (R$35.384 vs. R$25.352; p < 0,01).Conclusões:Mais de 60% dos pacientes estavam abaixo da meta desejada e os custos associados foram significativamente maiores nesta população.

Evaluation of the Validity of SAMe-TT2R2 Score in a Cohort of Venous Thromboembolism Patients Treated With Warfarin.

Low SAMe-TT2R2 score of <2 was validated as a predictor of optimum anticoagulation control, reflected by mean time in therapeutic range (TTR) above 65% to 70%, among warfarin-treated atrial fibrillation patients. This study aimed to validate the ability of SAMe-TT2R2 score and its individual components in predicting anticoagulation control (mean TTR and clinical events) among a cohort of venous thromboembolism (VTE) patients in Qatar. A total of 295 patients were retrospectively evaluated. There was a trend toward statistical significance in mean TTR between low (<2) and high (≥ 2) SAMe-TT2R2 score groups (P = .05), a difference that was not sustained when a cutoff of 3 was used (ie, a score of 3 or more). Patients with poor INR control (TTR <70%) were numerically less likely to have SAMe-TT2R2 score of <2 compared with those with good INR control, though the difference was not statistically significant (16.7% vs 83.3%, respectively, P = .4). No thromboembolic events were reported, and no association was found between the score and risk of bleeding. Non-Caucasian origin was the only significant predictor of good anticoagulation in the studied cohort. In conclusion, SAMe-TT2R2 score could not predict quality of anticoagulation control in a cohort of VTE patients treated with warfarin in Qatar. Contribution of other clinical factors and whether a different scoring may yield better prediction of anticoagulation control remains to be tested.

SAMe-TT2R2 in tunisian population: Results from the NATURE AF registry

Identifying patients who are likely to achieve and maintain a therapeutic international normalized ratio when prescribed a vitamin K antagonist (VKA) for stroke prevention in atrial fibrillation (AF) is challenging. The SAMe-TT 2 R 2 score was developed on the basis of common clinical factors that can highlight patients who may be unable to achieve and maintain good anticoagulation control. Our objective was to validate this score in a nationwide cohort of non-valvular AF patients. We studied a cohort of consecutive Tunisian patients with non-valvular AF who had oral anticoagulation. The baseline and 6-months SAMe-TT2R2 score was calculated. We included 915 patients, of whom 440 (48.1%) were male. Their median age was 65 years, median Cardiac failure or dysfunction, Hypertension, Age over 75 years [Doubled], Diabetes, Stroke [Doubled] - Vascular disease, Age between 65–74 and Sex category [Female] (CHA2DS2-VASc) score was 2 (0–9), and median Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score was 1 (0–5). The median SAME-TT2R2 score was 2 (0–8). At 12 months, the mean ± standard deviation time in therapeutic range was 48.9% ± 28.7% overall, and 110 patients (12.0%) had a time in therapeutic range value > 65%. Patients with a SAME-TT2R2 score 0 to 1 had a mean time in therapeutic range of 49.3% ± 30.4%, whereas patients with a SAME-TT2R2 score ≥ 2 had a mean time in therapeutic range of 48.7% ± 28.0% ( P 0.871). The odds ratio for having a low time in therapeutic range value was 1 (95% confidence interval, 0.9–1.0; P 0.871) for those patients with a SAME-TT2R2 score ≥ 2. In a “real-world” cohort of patients with atrial fibrillation and oral anticoagulation with VKA, there was no clinical value evidence of the SAME-TT2R2 score for the identification of patients who would have poor-quality anticoagulation.

Effect of multidose drug dispensing on the time in therapeutic range in patients using vitamin‐K antagonists: A randomized controlled trial

BackgroundA high number of vitamin K antagonist (VKA) users have a low proportion of time in therapeutic range (TTR) resulting in a high number of bleeding and thromboembolism events. ObjectiveCan the quality of anticoagulation be improved by dispensing VKAs via multidose drug dispensing (MDD). MethodA randomized controlled trial in the Netherlands. Patients who used VKAs, ≥65 years of age with a TTR <65% were eligible for inclusion. All oral drugs were dispensed via MDD. In MDD systems, all oral chronic medication intended for one dosing moment is packed in plastic disposable pouches. Controls received VKAs by manual dispensing. The difference in TTR between the 6 months after‐ and 6 months before the index date. A mixed‐effects model with the intervention, TTR before the index date, MDD system at baseline as covariates, and pharmacy as random effect. A per‐protocol analysis was performed with all patients who completed the study as intended. ResultsOne hundred and seventy‐nine patients were included. Mean age was 80.0 (SD 6.9) years. Mean TTR during the study was 79.2 ± 18.0% in the intervention group and 72.5 ± 20.1% in the control group. The intervention resulted in a 5.6% (95% CI: 0.1‐11.1) increase in TTR compared to the control group. Per‐protocol analysis resulted in an 8.3% (95% CI: 0.99‐15.61) increase in TTR compared to the control group. No differences in reduction were observed between the intervention and control group. ConclusionThe quality of anticoagulation can be improved with the use of MDD systems.

Health-related quality of life correlates with time in therapeutic range in children under anticoagulants with INR self-monitoring

In paediatrics, managing oral anticoagulant therapy with vitamin K antagonists (VKA) remains challenging. This study aimed to assess the correlation between time in therapeutic range (TTR) and quality of life (QoL) in children participating in a non-selective INR self-monitoring VKA-educational program. Children aged from 2 to 18 years under VKA therapy were eligible for this prospective multicentre study. Clinical and demographic data were collected. Health-related QoL was assessed using the PedsQL 4.0 questionnaire. Correlations between QoL scores and TTR were measured. A total of 121 children were included in the study (mean age 9.6 ± 4.9 years old). Cardiac conditions represented the predominant indication for VKA. The mean TTR was 0.78 ± 0.15, overall, and 0.76 ± 0.24 over the 3-month period before QoL assessment. The mean total QoL score was 76.2 ± 18 in self-reports, 71.4 ± 22 in mother-reports, and 73.5 ± 19 in father-reports. The TTR correlated with the total QoL scores, in self-reports ( r = 0.22, P = 0.04), mother-reports ( r = 0.23, P = 0.02), and father-reports ( r = 0.28, P = 0.02). The TTR predominantly correlated with school functioning in self-reports ( r = 0.38, P = 0.002) and mother-reports ( r = 0.40, P < 0.01), and with physical functioning in father-reports ( r = 0.28, P = 0.02). TTR correlated with QoL in children participating in a non-selective INR self-monitoring VKA-educational program. Regular assessment of QoL in patient education programs participates in understanding the concerns and needs of patients.

National Tunisian Registry of Atrial Fibrillation (NATURE-AF): Baseline results

Atrial fibrillation (AF) is an important health problem in Tunisia. A significant change in the epidemiological pattern of heart disease has been noticed. The purpose of the NATURE-AF registry was to determine the incidence of thrombo-embolic (TE) events and cardiovascular (CV) death at 1 year in patients with newly diagnosed AF. Secondary end points were to determine the incidence of hemorrhagic events and to calculate the mean time in therapeutic range (TTR) in patients receiving Vitamin K antagonists (VKA). NATURE AF is a multicenter, prospective study which enrolled 915 patients with AF between March and June 2017. The mean age was 64.2 ± 13.4 years (sex ratio 1.1). Common co morbidities were hypertension (53.4%), valvular disease (25.5%), diabetes (24.9%) and heart failure (HF)(14.4%). At one year the incidence of TE events was 1.64%. Ischemic stroke represented 53.3% of the total TE events. Heart failure (HF) and obstructive sleep apnea were the significant predictors of the TE events. CV mortality was 5.7%. HF was the only predictor factor of CV mortality. Hemorrhagic events occurred in 5.8% of the population among whom 0.5% had hemorrhagic stroke and 1% digestive hemorrhage. Hypertension, neoplasy and prescription of antiplatelet agents were the main significant predictors of hemorrhagic events. VKA were prescribed in 70.4% of the population (644 patients). The mean TTR was 48.9 ± 28.7%. TTR > 65% was noticed in 35% of the population. Patients receiving direct oral anticagulants (DOA) represented 2.2% of the population. NATURE AF reflects the epidemiological, therapeutic and outcome features of AF in the Tunisian population. The prevalence of valvular AF remains high. Control of the anticoagulation by VKA is poor. The use of DOA is low. These results highlight the need for other therapeutic choices in Tunisia particularly concerning anticoagulation.

Clinical Profile and One Year Outcome of Atrial Fibrillation- A Prospective Cohort Study

Introduction: Atrial Fibrillation (AF) is the most common arrhythmia in clinical practice and imposes a great burden on health care resources. There is limited data regarding the impact of AF in our population. Aim: To estimate the mortality and Major adverse Cardiovascular events {(MACE)- Acute Coronary Syndrome (ACS), Stroke, Cardiac death} in AF patients in a tertiary care centre in South India. Materials and Methods: This prospective cohort study included all patients &gt;18 years with newly diagnosed or previously documented evidence of AF in Electrocardiography (ECG). Transient reversible causes and critically ill patients were excluded. Total of 346 patients were recruited and prospectively, followed-up at 1, 3, 6 and 12 months for development of MACE, anticoagulation status, Prothrombin Time (PT), International Normalised Ratio (INR) and major bleeding events. Baseline data including clinical parameters, comorbidities and appropriate investigations such as ECG and Echocardiogram (ECHO) parameters were collected with a structured questionnaire and analysed at one year using appropriate statistical tests. Results: Average age was 60.5 years (SD 11.5 years) and majority (74.6%) were between 50-75 years. Females were more (59.5% vs 40.5%). Most common AF risk factor was Hypertension (44.5%) followed by Rheumatic Heart Disease (RHD) in 27.2% of AF patients. AF was classified as permanent in 42.2%, persistent in 23.1% and paroxysmal in 34.7%. Valvular AF was present in 26.6% and non-valvular AF in 73.4%. At one year, 17 patients were lost to follow-up. CHA2DS2VASc score of ≥2 was present in 65.1%. During one year follow-up the MACE rate was 26.7% (ischemic stroke in 9.4%, ACS in 2.7% and cardiac mortality in 14.6 %). Mean time in Therapeutic Range (TTR) was 28.12%. TTR &gt;60% (good control) was present in only 9.2%. Conclusion: AF continues to be a significant arrhythmia causing substantial morbidity and mortality. Non-valvular AF was thrice as common as valvular AF. Though 3/4th of the patients were on oral anticoagulants, &lt;10% had their INR under good control which contributed to the higher events. To improve the outcomes in AF patients, treatment of risk factors and optimal anticoagulation plays a crucial role.

Anticoagulation Challenges in Hematogeriatrics: Effectiveness and Safety of Direct Oral Anticoagulants Vs Vitamin k Antagonist in Elderly with Atrial Fibrillation

BACKGROUND Direct oral anticoagulants (DOAC) are increasingly used in patients with Non Valvular Atrial Fibrillation (NVAF) for stroke prevention. However, Follow-Up (FU) and dosing these agents in the elderly can be challenging due to different factors, such as chronic kidney disease, frailty, falls, multifactorial anemia and concomitant polypharmacy. These factors in elderly patients predisposes to both thromboembolic and bleeding events once atrial fibrillation occurs. Therefore, balancing risks and benefits of antithrombotic strategies in older populations is crucial. Despite recent increases in DOAC use in NVAF, there are still limited data regarding DOACs effectiveness and safety in frail elderly patients. AIM To assess the effectiveness and safety according to DOAC or Vitamin K Antagonist (VKA) in a cohort of elderly patients with NVAF. METHODS From April 2016 to April 2019, we consecutively included NVAF elderly patients (≥80 years-old) treated with DOAC or VKA in a prospective multicenter registry. Demographic, laboratory, frailty risk stratification and antithrombotic therapy data were collected. Patients had a minimum FU of 6 months. VKA patients had a standard FU through digital international normalized ratio (INR) control and the efficacy of therapy was determined by the time in therapeutic range (TTR) values from the preceding 6 months of treatment using Rosendaal's method. FU in DOAC patients was performed through structured and integral assessment following the Tromboc@t Working Group recommendations for management in patients receiving DOAC (Olivera et al, Med Clin 2018). Key practical management aspects are listed in the flow chart (Figure 1). Clinical Frailty Scale (CFS score) was assigned to each patient at the beginning and during the FU; patients were classified into three categories: non-frail (CFS 1-4), mild-to-moderately frail (CFS 5-6), and severely frail (CFS 7-9). RESULTS From a total of 1040 NVAF patients, 690 (63.5%) were treated with DOAC (61 dabigatran, 95 rivaroxaban, 254 edoxaban and 280 apixaban) and 350 with VKA. In the VKA group, the mean TTR was 52.8%. Demographic characteristics and CFS score are summarized in table 1. Kaplan-Meier analysis (median FU: 16.5 months) showed a significantly high incidence of stroke/systemic embolism among VKA patients vs DOAC patients (4.2 vs 0.5 events per 100 patient-years, p&lt;0.001). Major bleeding in the DOAC group was significantly infrequent compared with VKA group (2.2 vs 8.9 events, p=0.001). In the DOAC group, 90% (n=20/22) of the major bleedings were gastrointestinal [16 rivaroxaban and 4 edoxaban]. However, in the VKA group 64% (n = 20/31) were gastrointestinal, 25.8% (n= 8/31) intracranial and 9.7% (n = 3/31) urogenital bleedings. We identified 365 very elderly patients (aged ≥ 90 years) of which 270 (39.1%) were DOAC patients and 95 (27.1%) VKA patients. In this subgroup of patients, after a multivariate regression analysis, the stroke/systemic embolism incidence was similar in both treatment groups regardless of the age, but major bleeding decreased significantly in DOAC group (adjusted HR 0.247, 95% CI 0.091-0.664). CONCLUSIONS Our data indicate that DOACs can be a good therapeutic option for stroke/systemic embolism prevention in frail elderly patients, showing low rates of stroke as well as bleeding events when a structured and integral FU is applied to anticoagulated patients. Further investigations are necessary to analyze the impact in the quality of life and net clinical benefit of anticoagulant therapy when a FU program is applied in elderly patients. Disclosures Sierra: Novartis: Honoraria, Research Funding, Speakers Bureau; Astellas: Honoraria; Pfizer: Honoraria; Daiichi-Sankyo: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Roche: Honoraria; Jazz Pharmaceuticals: Honoraria.

P2753Anticoagulation control and all-cause death in patients with operated valvular heart disease with and without atrial fibrillation receiving vitamin K antagonists

Abstract Introduction Good quality of anticoagulation in patients with valvular heart disease (VHD) is needed to reduce ischaemic complications. There is limited evidence on factors affecting anticoagulation control in patients implanted with mechanical or tissue prosthetic valve(s). Objective To examine quality, factors affecting anticoagulation control and all-cause death in VHD patients with and without atrial fibrillation (AF) receiving a vitamin K antagonist (VKA) oral anticoagulant. The relationship between INR control with all-cause death and ≥1 adverse clinical events (ACE) [thromboembolism, bleeding, cardiovascular hospitalisation and all-cause death] were explored. Methods Anticoagulation control of 456 VHD patients [164 (36%) with AF and 290 (64%) without AF] referred to a hospital-based anticoagulation clinic were assessed retrospectively by time in therapeutic range (TTR) (Rosendaal) and percentage of INRs in range (PINRR) for a median of (IQR) 6.2 years (3.3–8.5). VHD was defined by the presence of mechanical or tissue prosthetic valve at either the mitral or aortic site or both. Results Mean (SD) age 51 (14.7), 64.5% male, mean (SD) CHA2DS2-VASc score 2.0 (1.4), 96.1% mechanical prosthesis and 64% aortic valve replacement. VHD patients with AF had lower mean TTR and PINRR, lower proportion of optimal TTR (i.e.≥70%) despite similar number of INR tests compared to VHD patients without AF [Table 1]. Predictors of poor TTR on multivariate logistic regression analysis were female sex, AF and anaemia/bleeding history. Significantly higher proportions of VHD patients with AF died [Table 1]. More deaths (13.1% vs. 4.1%; p=0.011) and ≥1 ACE (42.7% vs. 27.6%; p=0.006) were seen in VHD patients with TTR &lt;70% vs. TTR≥70%, respectively. Table 1 N (%) Total (N=456) AF (N=164) No AF (N=290) p-value Mean (SD) TTR 58.5 (14.6) 55.7 (14.2) 60.1 (14.6) 0.002 TTR ≥70% 98 (21.5) 23 (14.0) 75 (25.7) 0.004 Mean (SD) PINRR 50.1 (13.8) 47.4 (13.5) 51.6 (13.7) 0.002 Mean (SD) INR tests 96.2 (55.3) 100.7 (58.8) 93.7 (53.1) 0.19 All-cause death 51 (11.2) 34 (20.7) 17 (5.8) &lt;0.001 AF: Atrial fibrillation; IQR: interquartile range; PINRR: percentage of INRs in range; SD: standard deviation; TTR: Time in therapeutic range. Conclusion The quality of anticoagulation in VHD patients with AF was low. The presence of AF, anaemia/bleeding history and female sex independently predicted poor TTR. All-cause death was more common in VHD patients with AF and poor TTR. Closer INR monitoring is needed especially in VHD patients with AF to improve anticoagulation control and prevent adverse clinical outcomes. Acknowledgement/Funding Kementerian Pendidikan Malaysia and Universiti Teknologi MARA for PhD study but not directly for work under consideration

Health-related quality of life correlates with time in therapeutic range in children under anticoagulants with INR self-monitoring

In paediatrics, managing oral anticoagulant therapy with vitamin K antagonists (VKA) remains challenging. This study aimed to assess the correlation between time in therapeutic range (TTR) and quality of life (QoL) in children participating in a non-selective INR self-monitoring VKA-educational program. Children aged from 2 to 18 years under VKA therapy were eligible for this prospective multicentre study. Clinical and demographic data were collected. Health-related QoL was assessed using the PedsQL 4.0 questionnaire. Correlations between QoL scores and TTR were measured. A total of 121 children were included in the study (mean age 9.6 ± 4.9 years old). Cardiac conditions represented the predominant indication for VKA. The mean TTR was 0.78 ± 0.15, overall, and 0.76 ± 0.24 over the 3-month period before QoL assessment. The mean total QoL score was 76.2 ± 18 in self-reports, 71.4 ± 22 in mother-reports, and 73.5 ± 19 in father-reports. The TTR correlated with the total QoL scores, in self-reports ( r = 0.22, P = 0.04), mother-reports ( r = 0.23, P = 0.02), and father-reports ( r = 0.28, P = 0.02). The TTR predominantly correlated with school functioning in self-reports ( r = 0.38, P = 0.002) and mother-reports ( r = 0.40, P < 0.01), and with physical functioning in father-reports ( r = 0.28, P = 0.02). TTR correlated with QoL in children participating in a non-selective INR self-monitoring VKA-educational program. Regular assessment of QoL in patient education programs participates in understanding the concerns and needs of patients.

The SAMe-TT2R2 Score Predicts Warfarin Control in an Australian Population with Atrial Fibrillation.

Background: Warfarin requires regular monitoring with the time in therapeutic range (TTR), a common indicator of control and TTR > 70% is indicative of efficient anticoagulation. The SAMe-TT2R2 (sex, age, medical history, treatment, tobacco use, race) model has been utilised as a predictor of warfarin control, with a score ≥ 2 indicative of poor control. However, it has been suggested that race may be over-represented in this model. To date, no Australian studies have applied this model, possibly because race is not routinely recorded. Therefore, the aim of this study was to apply the SAMe-TT2R2 model in an Australian population on warfarin managed by both a warfarin care program (WCP) and general practitioner (GP). Methods: Retrospective data was collected for patients receiving warfarin via a WCP in Queensland and whilst being managed by a GP. Patient data was used to calculate the SAMe-TT2R2 score and the TTR for each patient. Mean TTR was used for analysis and comparison with the categorised SAMe-TT2R2 score. Results: Of the 3911 patients managed by a WCP, there was a significantly lower mean TTR for patients with a SAMe-TT2R2 score ≥ 2 compared to 0–1 (78.6 ± 10.7% vs. 80.9 ± 9.5%, p < 0.0001). Of these patients, 200 were analysed whilst managed by a GP and the categorised SAMe-TT2R2 score did not result in a statistically different mean TTR (69.3 ± 16.3% with 0–1 vs. 63.6 ± 15.0% with ≥2, p = 0.089), but a score ≥2 differentiated patients with a TTR less than 65%. Conclusions: The SAMe-TT2R2 model differentiated Australian patients with reduced warfarin control, despite the exclusion of race. In Australia, the SAMe-TT2R2 score could assist clinicians in identifying Australian patients who may obtain reduced warfarin control and benefit from additional interventions such as a dedicated WCP.

ICUSI questionnaire validation. Quality of anticoagulation in patients with atrial fibrillation treated with vitamin K antagonists

Introduction and objectivesVitamin K antagonists (VKAs) are still widely used for stroke prevention in atrial fibrillation. However, the access to international normalised ratio (INR) determinations is sometimes difficult and the time in therapeutic range (TTR) is not always available. The aim of this study was to design and validate a simple and easy-to-use questionnaire that enables the identification of atrial fibrillation patients with poor quality of anticoagulation. MethodsThis is a national, multi-centre, observational, and cross-sectional study including consecutive non-valvular atrial fibrillation patients receiving VKA therapy and followed up at cardiology clinics. At inclusion, INR determinations during the last 6 months were analysed to determine the TTR and the ICUSI questionnaire was completed. A TTR < 65% was considered suboptimal. ResultsA total of 813 patients (55% men, 75±9 years old) were available for the analyses. The mean TTR was 62.2%±20.3% and 427 (52.5%) patients had a TTR < 65%. The final version of the ICUSI questionnaire included 4 questions and the mean ICUSI score was 1.19±1.17. The predictive ability of the ICUSI questionnaire for predicting TTR < 65% was moderate (c-index, 0.707; 95%CI, 0.670–0.740; P<.001). An ICUSI score of 1 showed a sensitivity of 80.8% and a specificity of 45.6%, whereas an ICUSI score of 2 showed a sensitivity of 43.2% and a specificity of 88.1%. ConclusionsThe ICUSI questionnaire has shown a good predictive performance for the identification of poor TTR in the absence of full access to the INR determinations in atrial fibrillation patients under VKA therapy.

PCV80 RELATIONSHIP BETWEEN OPTIMAL WARFARIN CONTROL AND DISTANCE TO DISPENSING PHARMACIES IN AN UNDERSERVED URBAN POPULATION

Few studies have explored the impact of transportation to pharmacies on outcomes in patients receiving anticoagulation therapy. Our aim is to explore the relationship between patient’s travel distance and time to their dispensing pharmacy on the quality of warfarin control in an underserved urban population. English-speaking adults receiving long-term warfarin therapy from an ambulatory Anti-Thrombosis Clinic completed an interview-administered questionnaire. Patients’ residential address and pharmacy locations were geocoded using SAS 9.4 GEOCODE procedure. Geodetic distance was calculated between residence and pharmacy. Three-months of International Normalized Ratio (INR) was abstracted from the medical records to calculate time in therapeutic range (TTR) using the Rosendaal method. Acceptable control was defined as TTR ≥60%. Impact of travel distance or time to pharmacy on warfarin control was assessed using logistic regression. Patients who did not pick up their own medication or had missing INR data were excluded from logistic regression analysis. Of 144 recruited patients, mean (SD) age was 60 years (13.7), 102 (70.8%) African-American, 43 (29.9%) had income <$15,000, and 51 (35.4%) were disabled/unable to work. Twenty patients (13.9%) reported some trouble getting to their pharmacy. Most patients drove themselves (30.1%) or were driven by someone (26.6%). Of 104 patients, mean (SD) travel distance was 2.96 miles (3.81) and travel time was 22.2 minutes (20.3). Mean (SD) TTR was 61% (31%). Sixty-four (48.1%) patients had poor control. There was no significant association between anticoagulation control and travel distance or time. In this small sample of underserved urban patients, travel distance and time to pharmacy were not associated with warfarin control. However, some patients reported having trouble getting to their pharmacy. Transportation is only one of several factors that can affect warfarin control.