Anticoagulation Control Research Articles

Influence of renal function on vitamin K antagonist oral anticoagulation quality in non-valvular atrial fibrillation patients

Chronic kidney disease (CKD) has been related to poor quality of anticoagulation and an increased risk of bleeding. This study aims to evaluate the association between impaired renal function (eGFR < 60 mL/min/1.73 m 2 ) and anticoagulation control in patients with non-valvular atrial fibrillation (AF) on vitamin K antagonists (VKA) therapy. This is an ancillary analysis of the prospective NATURE AF registry (NAtionalTUnisianREgistry of Atrial Fibrillation). Between March and June 2017, we prospectively registered information of 912 patients with a recently diagnosed AF and they were followed for one year. Patients with CKD were in turn categorized according to their eGFR level (Stage 3A: 59–45 mL/min, Stage 3B: 44–30 mL/min, Stage 4:29-15 mL/min and Stage 5: < 15 mL/min). The calculations for the time in therapeutic range (TTR) were made for the 12 months in each group and compared with the TTR of patients without CKD. A total of 103 patients (11.4%) had eGFR < 60 mL/min/1.73 m 2 . Anticoagulation control levels progressively worsened across each stage of CKD till the stage 3B then it progressively improved in stages 4 and 5. In the subgroup of patients with preserved renal function (75.5%), the concomitant use of anti-platelet agents was associated with better TTR ( Table 1 ). Early stages of CKD seem to be associated with poorer anticoagulation control in patients with non-valvular AF taking VKA but without statistically significant difference. Larger studies with longer follow-up are necessary.

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.

Esophagectomy for Esophageal Cancer in a Patient with Protein C Deficiency: A Case Report

A 63-year-old man with protein C deficiency underwent thoracoscopic esophagectomy and digestive reconstruction using a gastric tube for thoracic esophageal cancer. On postoperative day 3, the gastric tube was removed because of anastomotic leakage and gastric tube necrosis. Digestive reconstruction using a free jejunal graft was attempted 140 days after the first surgery. However, thrombus formation in the artery and vein of the jejunal graft resulted in a failed reconstruction. Ten days after this surgery, digestive reconstruction using the colon was performed with intraoperative heparin administered for anticoagulation control. The surgery was successful, with no thrombus formation afterward. When performing digestive reconstruction in patients with conditions predisposing to thrombus formation, perioperative management should be completed with careful attention toward preventing thrombus formation. In particular, appropriate anticoagulation control, such as the administration of intraoperative heparin, is recommended in patients with protein C deficiency because necrosis of the reconstructed organ is likely.

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.

Treatment response and bleeding events associated with anticoagulant therapy of portal vein thrombosis in cirrhotic patients: Systematic review and meta-analysis.

BackgroundWell-defined guidelines for the treatment of portal vein thrombosis (PVT) in patients with cirrhosis are lacking, given the paucity of robust data. Among the available treatment options the best choice is unknown.MethodsWe conducted a comprehensive search of multiple electronic databases and conference proceedings (through December 2019) to identify studies that reported on the use of anticoagulants in the treatment of PVT in patients with cirrhosis. Our goals were to evaluate the pooled odds ratio (OR) and pooled rate of treatment responders and bleeding events.ResultsA total of 17 studies were included: 648 patients were treated with anticoagulation and 96 were controls. Pooled OR for treatment responders was 5.1 (95% confidence interval [CI] 2.5-10.2, P = 0.001) and pooled OR for bleeding was 0.4 (95%CI 0.1-1.5, P = 0.2) for anticoagulation treatment versus control. Pooled rate of treatment responders with anticoagulation was 66.7% (95%CI 58.3-74.1) compared to 26% (95%CI 14.2-42.7) for the control group. Pooled rate of bleeding seemed comparable (7.8%, 95%CI 4.5-13.3, and 15.4%, 95%CI 4.3-42.7). On subgroup analysis, pooled rates of treatment responders and bleeding events seemed similar between low molecular weight heparin, vitamin K antagonists, and direct oral anticoagulants.ConclusionsOur study demonstrated that anticoagulation is effective and safe in the treatment of PVT in patients with cirrhosis. Owing to the comparable outcomes, direct oral anticoagulants may be considered as first-line treatment, depending on patient preferences.

Impact of Anticoagulation Clinic Intervention on Patient Centred Outcomes in a Tertiary Care Hospital

Introduction: Vitamin K Antagonists (VKAs) have been in use for more than 50 years. They have remained as mainstay therapy in the prevention of thromboembolic events in atrial fibrillation, mechanical heart valves and venous thromboembolism. Despite many years of clinical experience with VKAs, the quality of anticoagulation achieved in routine clinical practice is suboptimal. Aim: To study the effects of structured Anticoagulation Clinic (ACC) interventions on patient centred outcomes in subjects taking VKAs. Materials and Methods: A retrospective study was conducted among patients taking VKAs enrolled in ACC. A total of 169 patients receiving VKAs for at least six months with 4 INR (International Normalised Ratio) values and completed 12 months of follow-up were analysed. Anticoagulation related quality measures like Time in the Therapeutic Range (TTR), Percentage of International Normalised Ratios in the therapeutic Range (PINRR) and clinical outcomes like stroke, systemic embolic events and bleeding was analysed at the time of enrolment and compared with those during ACC care. Results: Among 352 patients enrolled in ACC, 169 patients were eligible for analysis. The mean age of the study population was 55.62±13.77 years. Atrial fibrillation (59%) was the most common indication for VKA therapy. Hypertension (66.3%) was the most common co-morbidity. Mean TTRs were significantly higher in the ACC care when compared with the pre-ACC care at 12 months follow-up (77.58±8.85% vs 51.01±16.7%, p&lt;0.0001). There was a significant improvement in TTRs as early as three months of ACC intervention (73.18±13.56%). At the time of enrolment, 21.9% of patients had individual TTRs (i-TTR) &gt;70% which increased to 70.4% at 12 months of follow-up. INR testing was done more frequently in ACC care. Adverse clinical events were higher in pre-ACC care than ACC care (4.7% vs 2.4%, p&gt;0.05). Major bleeding and thromboembolic events were higher in pre-ACC care than ACC care (1.8% vs. 0.6% and 2.4% vs. 0.6% respectively). Conclusion: ACC services helps in achieving better quality of anticoagulation control as measured by time in therapeutic range translating into better clinical outcomes.

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.

Factors associated with sub-optimal control of anticoagulation in patients with prosthetic heart valves taking oral anticoagulants in a sub-Saharan African setting.

Replacement of diseased valves reduces the morbidity and mortality rate associated with native valvular disease but comes at the expense of risking complications related to the implanted prosthetic device. Establishing the desired anticoagulation level in a sub-Saharan African setting may be a challenge. This study was conducted to determine the challenges of maintaining a desired level of anticoagulation and factors associated with sub-optimal anticoagulation in patients with prosthetic heart valves on chronic anticoagulation. We reviewed 73 patients who had undergone prosthetic valve replacement for chronic rheumatic valvular heart disease and were taking warfarin. The follow up ranged from one to 13 years. We studied international normalised ratio (INR) profiles of the patients for the six months preceding the study and defined optimal control as an INR of 2.5-3.5. We aimed to determine if there were factors associated with sub-optimal control of INR. Forty-two patients (57.5%) were female. Mean age of the participants was 21.5 ± 3.1 years (range 14-25 years). Warfarin was the anticoagulant in 55 (75.3%) of the patients and 18 (24.7%) were on combined warfarin and aspirin anticoagulation. Thirty-five (47.9%) patients had optimal control of their INR. Educational level of primary school or less, distance from follow-up medical facility of more than 300 km, quarterly or less-frequent check-up visit, and public health institution as a source of free warfarin supply were found to be significantly associated with sub-optimal control of INR. Educational level, distance from follow-up facility, number of follow-up visits and source of warfarin supply were found to be significantly associated with sub-optimal control of INR.

Flexitrate regional citrate anticoagulation in continuous venovenous hemodiafiltration: a retrospective analysis

BackgroundFlexitrate, an innovative regional citrate anticoagulation (RCA) protocol, was compared to traditional RCA (tRCA) and Heparin anticoagulation protocols in intensive care patients treated with continuous renal replacement therapy (CRRT).MethodsA single-center, retrospective, cohort study, was done in a 26-bed intensive care unit in a large community hospital. Eighty dialysis sessions (Flexitrate = 2852 h, tRCA = 3580 h and Heparin = 2026 h), performed in 53 patients, were evaluated for filter life, RCA control, and metabolic control.ResultsIn the Flexitrate cohort, 3.8% of filters clotted, compared to 16.9% with tRCA and 28.3% with Heparin (p < 0.001 for Flexitrate compared to either tRCA or Heparin). Filter survival was significantly improved with Flexitrate compared to tRCA (HR 0.24, p = 0.018) or Heparin (HR 0.14, p = 0.004).Anticoagulation control was superior with Flexitrate with Patient Ionized Calcium out of target a median of 16% of the time, compared to 27% for tRCA (p < 0.001). Filter Ionized Calcium was out of target a median of 6.8% of the time, compared to 23% for tRCA (p = 0.03).Flexitrate produced significantly less alkalosis, hypernatremia, and hypocalcemia than tRCA, and overall metabolic control was comparable to Heparin anticoagulation. The only adverse metabolic outcome with Flexitrate was increased hypomagnesemia.ConclusionsThe Flexitrate protocol extended filter life, delivered more consistent anticoagulation, and provided superior metabolic control compared to a tRCA protocol. Filter life was superior to Heparin anticoagulation, with similar metabolic control. A randomized control trial comparing these protocols is recommended.

Efficacy and Safety of Direct Oral Factor Xa Inhibitors in Patients after Bariatric Surgery

Background: Over 200,000 people underwent weight loss surgery in the United States in 2017. The absorption of numerous drugs has been shown to be altered in patients after bariatric procedures, as gastrointestinal absorptive surface, food volume, and gastric pH all affect bioavailability. Dosing of warfarin, which is commonly used for the treatment of venous thromboembolism (VTE), often needs to be adjusted, based on INR, after bariatric surgery. Since direct oral anticoagulants (DOACs), which are rapidly replacing warfarin as standard anticoagulant therapy, are not monitored, there is concern regarding their efficacy and safety in patients who have had bariatric surgery, particularly rivaroxaban, which is absorbed primarily in the stomach and must be taken with food at therapeutic doses. One study found that 9 out of 9 apixaban patients (but only 2 of 7 rivaroxaban patients) had levels that fell within the expected range after bariatric surgery. Effects of bariatric surgery on DOACs may be further complicated by baseline obesity and subsequent weight loss of the patients. The goal of our current study is to determine whether DOACs are safe and effective in preventing recurrent VTE in patients who have undergone bariatric surgery. Methods: Using our institutional database, we identified all adult patients (age ≥18 years) with a history of bariatric surgery (gastric banding, sleeve gastrectomy, and Roux-en-Y gastric bypass) who were started on anticoagulation with apixaban or rivaroxaban for VTE, between July 1, 2013 and June 30, 2018. We performed retrospective chart review to obtain information on patient demographics, BMI and type of bariatric surgery. We documented clinical outcomes of recurrent VTE and bleeding from the first prescription date to the earliest of a thrombotic event, discontinuation of medication, death, or the end of study period, June 30, 2018. VTE events were confirmed by a review of imaging studies (compression ultrasonography, ventilation/perfusions scans, and CT scans). Bleeding events were included if they met criteria for clinically relevant non-major bleeding and/or major bleeding according to the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Safety outcomes included major bleeding (MB) and clinically relevant non-major bleeding (CRNMB). We also compared VTE recurrence and bleeding rates between the post-bariatric surgery patients and patients with BMI &gt;40 from our prior study. Chi- squared tests were used to assess statistical significance of the differences in recurrent VTE and bleeding rates between anticoagulant cohorts. Results: Data on 102 patients were collected: 42 patients on apixaban and 60 patients on rivaroxaban. Our population was predominantly female (82.4%) with a mean age of 48.5 years and a median BMI of 35.7 at initiation of anticoagulation. Gastric bypass was the most common bariatric procedure (51%), followed by sleeve gastrectomy (37.3%), and gastric banding (11.8%). There were no recurrent VTE events in the apixaban cohort with a median follow-up duration of 137 days. Among patients on rivaroxaban, with a median follow-up of 232 days, there was one recurrent VTE (1.7%) in a patient with a BMI of 54 at the time of event. When we compared VTE recurrence rates of our combined DOAC cohort (apixaban + rivaroxaban) between our general morbidly obese population, from a prior study at our institution, and post-bariatric surgery patients, there was no statistically significant difference (2.0% vs. 1.0%, respectively, p=0.5). In bariatric surgery patients, one CRNMB event was recorded in apixaban group (2.4%) while 4 major bleeding events occurred on rivaroxaban (6.7%), p=0.3. There was no significant difference in the rate of composite MB and CRNMB between the general obesity and bariatric surgery patients (8.0% vs. 4.9%, respectively, p=0.3). Conclusions: In a review of post-bariatric surgery patients on anticoagulation for VTE, we found low rates of recurrent VTE for patients on DOACs. Although we had a relatively small sample size, the incidence of VTE recurrence was not higher in this cohort than was found in our previously published study of general obesity population. Prospective studies are needed to further investigate the efficacy and safety of direct oral anticoagulants in patients after bariatric surgery. Table. Disclosures Kushnir: Janssen Pharmaceuticals: Research Funding. Billett:Janssen: Research Funding.

Non-genetic factors and polymorphisms in genes CYP2C9 and VKORC1: predictive algorithms for TTR in Brazilian patients on warfarin.

This study was designed to evaluate the association of non-genetic factors and polymorphisms CYP2C9*2 (rs1799853), CYP2C9*3 (rs1075910), and VKORC1-G1639A (rs9923231) with time in therapeutic range (TTR), and to build a regression model to predict the quality of oral anticoagulation control in a sample of Brazilian patients. This is a retrospective cohort study developed at an anticoagulation clinic of a university hospital. Overall, 312 patients were included. The quality of oral anticoagulation control was evaluated by TTR. TTR was dichotomized for analysis, using two cutoff points for classification as inadequate (TTR ≤ 60.0%) and optimal (TTR ≥ 75.0%) control. The average age was 60.4 ± 13.5 years, with a predominance of women (187; 59.9%). The -G1639A polymorphism of the VKORC1 gene, when evaluated, based on the recessive inheritance pattern [AA × (GA + GG)], patients with AA genotype exhibited a higher TTR (68.2% versus 62.8%, p = 0.017). TTR ≤ 60.0% was associated with number of drugs in chronic use, assistance for warfarin administration, reports of not taking warfarin, absenteeism, sex (female), and target INR (International Normalized Ratio; 2.00-3.00). TTR ≥ 75.0% was associated with sex (male), target INR (2.00-3.00), assistance for warfarin administration, reports of not taking warfarin, and absenteeism. The two algorithms proposed showed adequate ability to predict TTR presenting good sensitivity and specificity. Our findings provided useful information for risk stratification depending on TTR level and for future investigations on the quality of oral anticoagulation control in Brazilian anticoagulation clinics.

PCV127 PATIENT PREFERENCES REGARDING ORAL ANTICOAGULANTS: RESULTS OF A DISCRETE CHOICE EXPERIMENT IN SPANISH PATIENTS WITH ATRIAL FIBRILLATION TREATED WITH VITAMIN-K ANTAGONISTS

Oral anticoagulation is pivotal in the management of thromboembolic risk in non-valvular atrial fibrillation (NVAF) patients. An effective anticoagulation therapy also relates on good medication adherence to achieve good anticoagulation control. One key element for reaching or sustaining a good adherence and persistence is to prescribe treatments that patients prefer. The objective of this study was to elucidate patient preferences regarding attributes that describe different anticoagulation alternatives. A multi-center discrete choice experiment (DCE) was conducted in Spain. Study sites enrolled patients aged 18+ years with NVAF, who initiated a Vitamin-K antagonist (VKA) treatment. The DCE design considered four treatment attributes: need of bridging (yes/no), interactions with food/alcohol (yes/no), need of regular international normalized ratio (INR) assessments/blood controls and subsequent dose adjustment (yes/no) and frequency of intake (once/twice daily). Distance to treating practitioner represented a neutral attribute to express patients’ overall utility in terms of a comprehensible unit. Conditional logit regression model was applied to estimate patients’ utility for each attribute and to evaluate the influence of different levels on the probability of a patient of choosing a specific OAC alternative. In total, 286 patients were included (mean age: 72.9 years, 42.0% female, mean CHA2DS2-VASc: 3.2). Patients preferred an anticoagulation treatment option characterized by “no need for bridging” (β=0.530, p<0.001), “no need for regular INR controls” (β=0.652, p<0.001), “less interactions with food/alcohol” (β=0.503, p<0.001) and “once daily intake” (β=0.360, p<0.001). To receive such a treatment option compared to a treatment that offers none of the favourable characteristics, the average patient would be willing to travel additional 57 kilometres to the treating practitioner. In our study, NVAF patients currently treated with VKA showed a strong preference for features that characterize non-VKA anticoagulation options.

Personalised Warfarin Dosing in Children Post-cardiac Surgery

Warfarin dosing is challenging due to a multitude of factors affecting its pharmacokinetics (PK) and pharmacodynamics (PD). A novel personalised dosing algorithm predicated on a warfarin PK/PD model and incorporating CYP2C9 and VKORC1 genotype information has been developed for children. The present prospective, observational study aimed to compare the model with conventional weight-based dosing. The study involved two groups of children post-cardiac surgery: Group 1 were warfarin naïve, in whom loading and maintenance doses were estimated using the model over a 6-month duration and compared to historical case-matched controls. Group 2 were already established on maintenance therapy and randomised into a crossover study comparing the model with conventional maintenance dosing, over a 12-month period. Five patients enrolled in Group 1. Compared to the control group, the median time to achieve the first therapeutic INR was longer (5 vs. 2 days), to stable anticoagulation was shorter (29.0 vs. 96.5 days), to over-anticoagulation was longer (15.0 vs. 4.0 days). In addition, median percentage of INRs within the target range (%ITR) and percentage of time in therapeutic range (%TTR) was higher; 70% versus 47.4% and 83.4% versus 62.3%, respectively. Group 2 included 26 patients. No significant differences in INR control were found between model and conventional dosing phases; mean %ITR was 68.82% versus 67.9% (p = 0.84) and mean %TTR was 85.47% versus 80.2% (p = 0.09), respectively. The results suggest model-based dosing can improve anticoagulation control, particularly when initiating and stabilising warfarin dosing. Larger studies are needed to confirm these findings.

P3815Cost and burden of poor control of the level of anticoagulation in patients with non-valvular atrial fibrillation treated with vitamin K antagonist in the Spanish National Health Service

Abstract Introduction Poorly controlled non-valvular atrial fibrillation (NVAF) patients treated with vitamin K antagonists (VKA) experience higher rates of clinical events compared to well controlled patients. In Spain a high percentage of NVAF patients present an inadequate control of anticoagulation therapy, whose economic impact has not been reported yet. Purpose To estimate the impact on resource consumption, clinical events and mortality of poorly controlled NVAF patients≥65 years treated with VKA in Spain. Methods A cost-consequence analytic model was developed to estimate differences on clinical events and cost between poorly controlled (TTR&lt;65%) and well controlled (TTR≥65%) NVAF patients treated with VKA over 1 year. A hypothetical cohort of NVAF patients was estimated by using local epidemiological studies. Anticoagulation control rates, as measured by Rosendaal method, were retrieved from a literature review of Spanish real-world studies. Clinical event rates (ischemic stroke-IS-, hemorrhagic stroke-HS-, major bleeding-MB-, systemic embolism-SE- and death for any cause) were derived from a post-hoc analysis of SPORTIF III/V trials. A sensitivity analysis (SA) was performed by using event rates from a prospective single-center study carried out in Spain. Societal and National Health Service (NHS) perspectives were considered. Total annual costs (€ 2018) included clinical event direct, non-direct healthcare cost and indirect-costs. Potential life years lost (PLYL) were calculated to report impact on mortality. An expert panel composed by a cardiologist, a haematologist and general practitioners validated the model inputs. Results The target population comprised 594,855 NVAF patients treated with VKA (mean age 73.2 years, 49.4% women, 74.1% CHADS≥2). Poorly controlled anticoagulated patients accounted for 48.3% of the cohort. The inadequate control of anticoagulation was associated with a higher incidence of clinical events compared to well controlled patients within a year (additional 2,143 IS, 390 HS, 201 SE, 6,190 MB and 6,856 deaths). From NHS perspective, the incremental total annual costs associated to poorly controlled patients were €46,685,756.60 (€173.96/patient-year). When considering the societal perspective, the incremental total annual costs of inadequate anticoagulation control reached €97,787,872.59 (€367.51/patient-year). Mortality due to poorly anticoagulation control implied 80,830.65 PLYL (0.136 PLYL/patient-year). The SA confirmed the base case results. Conclusions In the Spanish NHS, around 50% of NVAF patients ≥65 years treated with VKA present an inadequate control of the anticoagulation therapy (287,089 patients), which is associated with the increase of clinical events, mortality and costs (up to €100 million). The results of this study highlight a call to action to increase the awareness of the consequences of a poor anticoagulation control and emphasize the need for a better clinical of patients receiving anticoagulation. Acknowledgement/Funding BMS and PFIZER contributed to finance the no conditioned to the results of this work.

Impact of a pharmacist-led education and follow-up service on anticoagulation control and safety outcomes at a tertiary hospital in China: a randomised controlled trial.

This study was designed to evaluate the impact of a pharmacist-led anticoagulation service on international normalised ratio (INR) control and other outcomes among patients receiving warfarin therapy at a tertiary hospital in Zhuhai, China. In this randomised controlled trial, adult patients who were newly initiated on warfarin with intended treatment duration of at least 3months were recruited. Participants were randomly allocated to receive the pharmacist-led education and follow-up service (PEFS) or usual care (UC). Anticoagulation control was calculated as the proportions of time within the target INR range (TTR) and time within the expanded target range (TER). A total of 152 participants (77 in the PEFS group and 75 in the UC group) were included. Within 180days after hospital discharge, the PEFS group spent more TER than the UC group (54.4% versus 42.0%; P=0.024), whereas the difference in TTR did not reach statistical significance (35.9% versus 29.5%; P=0.203). No major bleeding events were observed, and the cumulative incidences of major thromboembolic events (6.5% versus 9.3%) and mortality (1.3% versus 1.3%) were similar between the two groups (P>0.05). At 30days postdischarge, the PEFS group had better warfarin knowledge by answering 57.5% of questions correctly, compared with the UC group (43.0%) (P=0.003). The PEFS markedly enhanced anticoagulation control and warfarin knowledge but there was room for improvement. The expansion of pharmacists' clinical role and the development of more effective education and follow-up strategies are warranted to optimise anticoagulation management services in China.

P4765Men who live alone have poor anticoagulation control: results from Danish registries

Abstract Background Efficacy and safety of vitamin K antagonists (VKAs) depend on quality of anticoagulation control, usually measured as time in therapeutic range (TTR). Factors that predict low TTR on VKAs could be used to identify patients who might benefit from interventions, or who would be better treated with a non-VKA oral anticoagulant (NOAC). Patients living alone may have difficulties in taking their medications, managing their diets, or coming to clinic for monitoring. Purpose To assess influence of cohabitation status on TTR with VKA among men and women. Methods We identified all Danish patients with atrial fibrillation (AF) who initiated VKA between 1997 and 2012, and studied patients who had 6 months of continuous VKA use and international normalized ratio (INR) monitoring. Patients were divided according to sex and whether they lived alone or with others. We calculated TTR using the Rosendaal method, and INR variability using Fihns method. We used a linear regression model to test for associations between TTR and covariates, and adjusted for age, income, medications and comorbidities. Results We identified 4,772 AF patients with 6 months of continuous VKA use and INR monitoring. 713 (15%) were men living alone, 1,073 (23%) were women living alone, 2,164 (45%) were men not living alone and 822 (17%) were women not living alone. INR was measured a median of 11 (interquartile range 8–15) times during the 180 days of VKA use, but men who lived alone had 0.6 (95% confidence interval (CI): 0.2 to 1.2) fewer INR measurements during the period. Median TTR was lowest among men living alone (57.2%), followed by women living alone (58.8%), women not living alone (61.0%) and men not living alone (62.5%). After multivariable adjustment, men who lived alone had a 3.6% (CI −5.6 to −1.6) lower TTR compared with men not living alone, but women who lived alone did not have significantly lower TTR (P=0.80) compared with women not living alone. Living alone had significantly greater effect on TTR among men than among women (interaction P=0.02). Men living alone also had higher adjusted INR variability (0.2, CI 0.0 to 0.4) compared with men not living alone. Conclusion Living alone was significantly related to low quality of anticoagulation control among men, but not among women. Acknowledgement/Funding this study was funded by an unrestricted grant from the Capital Region of Denmark, Foundation for Health Research

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

OUTCOMES OF AN ATRIAL FIBRILLATION PATIENT NAVIGATION DEMONSTRATION PROJECT

Atrial fibrillation (AF) is growing in prevalence and is associated with substantial health care utilization. Prompt anticoagulation (OAC), rate and rhythm control is critical in preventing sequelae of AF. Connecting patients to secondary prevention (exercise, weight loss) through cardiac rehabilitation (CR) programs is also proven to decrease AF symptoms and recurrence. A January/February 2015 review of 60 consecutive patients presenting to the emergency department (ED) with a primary diagnosis of AF showed prolonged follow-up times and limited uptake of appropriate anticoagulation, likely secondary to concerns from ED physicians regarding lack of follow-up care. In March 2018, the AF navigation project was initiated to improve process of care through expedited telephone counseling by the AF navigator and subsequent care plan generation by the navigator and cardiologist, with best practice recommendations sent to family physicians. Referrals to specialty care and CR were made as needed. Here, the demonstration project results are compared to the 2015 review and a January/February 2018 review of 56 consecutive patients. For results, see Figure #1. To date, 129 patients have been referred to AF navigation. First telephone contact occurred, on average, in 2.4±1.8 days. Wait times (in days) to 1st in-person follow up have decreased from 26±36 in 2015 and 24±49 in Jan/Feb 2018 (n = 22) to 11±15 (p = 0.004). Only 4 (3%) AF navigation patients had a wait time greater than 31 days to their first follow-up appointment compared to 15 (25%) in 2015 (p < 0.05). ED prescribing of OAC occurred in 23% of AF navigation patients versus 0% in 2015 and 12% in Jan/ Feb 2018 (p = 0.005). 33% of AF navigation patients were started on OAC in follow up versus 17% of 2015 patients (p = < 0.05). For AF navigation patients with new onset AF, rate control was started by the ED in 44%, compared to 58% in 2015 and 71% in Jan/Feb 2018. 48% of AF navigation patients have accepted a referral to CR. A dedicated AF navigator reduces wait time to first in-person follow up for patients with AF, improves overall rates of anticoagulation and offers uptake into a secondary prevention program. Further analysis of health care utilization and outcomes of CR interventions is ongoing.

P3474Relationship between international normalized ratio variability, quality of anticoagulation control and outcomes in patients with atrial fibrillation: an AFFIRM post-hoc analysis

Abstract Introduction Quality of anticoagulation control is essential to ensure better clinical outcomes in patients with atrial fibrillation (AF). Time in therapeutic range (TTR) is recommended as a measure of the quality of anticoagulation control. The International normalized ratio (INR) variability has been suggested as an alternative index, even though large independent validations for this index are still lacking. Purpose To provide validation of clinical usefulness of INR variability as a measure of the quality of anticoagulation control in a large cohort of AF patients. Methods Data from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial were analysed. INR variability was defined as the standard deviation (SD) of mean INR values [INR-SD] recorded throughout the follow-up observation for each patient. All patients with available INR values were included in the analysis. Stroke, major bleeding, cardiovascular (CV) death and all-cause death were study outcomes. Results Among the original 4060 patients, a total of 3185 (78.4%) were available for analysis. Mean (SD) INR-SD was 0.58 (0.25). According to INR-SD patients were categorized into four quartiles. Mean (SD) CHA2DS2-VASc score was increased (p=0.040), with no difference in proportions of CHA2DS2-VASc ≥2 (p=0.582) between the subgroups. A significant inverse correlation was found between INR-SD and TTR (Spearman's Rho: −0.536, p&lt;0.001). Continuous INR-SD, after multiple adjustments, was inversely associated with TTR (standardized beta: −0.451, p&lt;0.001) and directly associated with SAMe-TT2R2score (standardized beta: 0.084, p&lt;0.001). A fully adjusted Cox multivariate regression analysis found that INR-SD was directly associated with increased risk of stroke, major bleeding and all-cause death (Table). An INR-SD ≥0.85 was directly associated with all the study outcomes, on multivariate analysis (Table). Cox Regression Analysis INR-SD INR-SD ≥0.85 HR (95% CI) HR (95%) Stroke 2.52 (1.34–4.67) 1.62 (1.00–2.63) Major Bleeding 2.43 (1.49–3.96) 1.61 (1.10–2.36) CV Death 1.50 (0.87–2.59) 1.54 (1.07–2.24) All-Cause Death 1.79 (1.21–2.66) 1.55 (1.17–2.05) CI = Confidence Interval; CV = Cardiovascular; HR = Hazard Ratio; INR-SD = International Normalized Ratio Standard Deviation. Conclusions INR variability, expressed as INR-SD, was significantly correlated and associated with TTR. Both continuous INR-SD and INR-SD ≥0.85 were significantly associated with a higher risk of all study adverse outcomes. Acknowledgement/Funding None

Polymorphisms of CYP2C9*2, CYP2C9*3 and VKORC1 genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.

IntroductionWarfarin continues to be the most widely used anticoagulant in clinical practice around the world for the prevention of thromboembolic events in patients with atrial fibrillation (AF). The evaluation of the quality of anticoagulation control, estimated by time in therapeutic range (TTR), is accepted as a good method to evaluate the quality of anticoagulation. The variability of TTR can be explained by the presence of variants of the CYP2C9 and VKORC1 genes.MethodsThis study examined the association between polymorphisms of the CYP2C9 and VKORC1 genes and control of oral anticoagulation, through TTR, in patients with AF. A cross-sectional study was conducted within a cohort follow-up. The study comprised of 317 patients with AF, using warfarin, who were followed up for one year. The genotyping of genes CYP2C9 (rs1057910), (rs1799853) and VKORC1 (rs923231) was performed by PCR in real time, using TaqMan probes.ResultsPatients who had variant genotypes for the CYP2C9*3 gene (rs1057910) presented higher TTR (TTR 81–100%) when compared to when compared to the <45% and 46–60% TTR groups (p=0.005 and p=0.002, respectively). Regarding VKORC1 (rs923231), patients who had the variant genotype for the VKORC1 (rs923231) gene also presented a higher TTR (TTR 81–100%), when when compared to the <45% and 46–60% TTR groups (p=0.005 and p=0.004, respectively). In a multivariate model, VKORC1 (rs923231) remained associated for comparisons with the TTR groups (<45% vs 81–100% groups, p=0.01; and 46–60% vs 81–100% groups, p=0.01).ConclusionThe genotypes of the CYP2C9*3 (AA) and VKORC1 -1639 (GG) genes were associated with the worst quality of anticoagulation control (TTR) in patients with AF using warfarin in the northeast of Brazil.