Impact of prior oral anticoagulant use and outcomes on patients from secondary analysis in the AUGUSTUS trial.

OBJECTIVE: Managing antithrombotic therapy in patients with atrial fibrillation (AF) and an acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI) is challenging and can be affected by prior oral anticoagulant (OAC) treatment. We examined the relationship between prior OAC use and outcomes in the AUGUSTUS trial. METHODS: This prespecified secondary analysis is from AUGUSTUS, an open-label, 2-by-2 factorial, RCT to evaluate the safety of apixaban versus vitamin K antagonist (VKA) and aspirin versus placebo in patients with AF and ACS and/or PCI. The primary endpoint, major or clinically relevant non-major bleeding and clinical outcomes were compared in patients receiving (n=2262) or not receiving (n=2352) an OAC prior to enrolment. RESULTS: Patients with prior OAC use had more comorbidities, higher CHA2DS2-VASC and HAS-BLED scores, and were more likely enrolled following elective PCI. There was no difference in major or clinically relevant non-major bleeding with or without prior OAC (30 days: 5.1% vs 5.9% (adjusted HR (aHR) 0.82, 95% CI 0.63 to 1.06); 180 days: 13.5% vs 13.5% (aHR 0.98, 95% CI 0.83 to 1.16)). Patients with prior OAC use had a lower risk of death or ischaemic events (30 days: 1.7% vs 2.8% (aHR 0.61, 95% CI 0.41 to 0.92); 180 days: 5.4% vs 7.6% (aHR 0.70, 95% CI 0.55 to 0.88)). No interactions between randomised treatment (apixaban vs VKA, aspirin vs placebo) and prior OAC status were observed for outcomes, apart from apixaban (vs VKA) being associated with a lower risk of myocardial infarction with prior OAC use (180 days: 2.0% vs 3.7% (aHR 0.56, 95% CI 0.33 to 0.91(). CONCLUSIONS: In AUGUSTUS, prior OAC use was associated with fewer ischaemic events but not more bleeding. In patients with AF and ACS and/or undergoing PCI, clinicians can be assured that the trial results can be applied to patients regardless of their prior OAC status. TRIAL REGISTRATION NUMBER: NCT02415400.

Management of Atrial Fibrillation in Patients 75 Years and Older: JACC State-of-the-Art Review.

The prevalence of atrial fibrillation (AF) is increasing as the population ages. AF treatment-related complications also increase markedly in older adults (defined as ≥75 years of age for this review). The older AF population has a high risk of stroke, bleeding, and death. Syncope and fall-related injuries are the most common reasons for nonprescription of oral anticoagulation (OAC), and are more common in older adults when OACs are used with antiarrhythmic drugs. Digoxin may be useful for rate control, but associations with increased mortality limit its use. Beyond rate and rhythm control considerations, stroke prophylaxis is critical to AF management, and the benefits of direct OACs, compared with warfarin, extend to older adults. Invasive procedures such as AF catheter ablation, pacemaker implantation/atrioventricular junction ablation, and left atrial appendage occlusion may be useful in appropriately selected cases. However, older adults have generally been under-represented in clinical trials.

Patient perception and treatment convenience of dabigatran versus vitamin K antagonist when used for stroke prophylaxis in atrial fibrillation: Real-world Evaluation of Long-term Anticoagulant Treatment Experience (RE-LATE) study.

PURPOSE: Dabigatran is a direct thrombin inhibitor approved for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF). Real-world data about patient preference, satisfaction and convenience in patients in Asia are not available. The study aimed to explore the perception of patients with newly diagnosed NVAF regarding dabigatran versus vitamin K antagonists (VKAs), when used for stroke prevention. PATIENTS AND METHODS: This was a multinational, multicentre, non-interventional study involving 49 sites across 5 countries in South East Asia and South Korea where 934 patients newly diagnosed with NVAF were initiated on either dabigatran (N=591) or VKA (N=343). Data were collected at baseline and over two follow-up visits across 6 months. Treatment satisfaction and patient convenience were evaluated using the Perception on Anticoagulant Treatment Questionnaire-2 (PACT-Q2). RESULTS: The mean age of the patients was 65.9±10.4 years, and 64.2% were male. Mean CHA2DS2-VASc score was 2.4±1.5, and mean HAS-BLED score was 1.2±0.9. At baseline, patients initiated on dabigatran had higher stroke risk, bleeding risk, creatinine clearance and proportion of patients with concomitant illnesses compared with patients initiated on VKAs. Treatment convenience was perceived to be significantly better with dabigatran versus VKAs at visits 2 and 3 (p=0.0423 and 0.0287, respectively). Treatment satisfaction was significantly better with dabigatran compared with VKAs at visit 3 (p=0.0300). CONCLUSION: In this study, dabigatran is associated with better patient perception in terms of treatment convenience and satisfaction compared with VKAs when used for stroke prevention in newly diagnosed NVAF patients from South East Asia and South Korea. TRIAL REGISTRATION NUMBER: NCT02849509. PLAIN LANGUAGE SUMMARY: Patient satisfaction with dabigatran versus VKAs in South East Asia. Patients with atrial fibrillation are at high risk of stroke and require anticoagulants for stroke prevention. Two such anticoagulants are dabigatran and VKAs. We wanted to compare the extent of satisfaction and treatment convenience among newly diagnosed patients with atrial fibrillation from the South East Asian region when they were given either dabigatran or VKAs. Consenting patients filled out a standardised questionnaire called the PACT-Q2 over three visits after they were started on either dabigatran (591 patients) or VKAs (343 patients). We found that satisfaction and convenience were significantly higher when patients received dabigatran than when they received VKAs.

Decision tree analysis to predict the risk of intracranial haemorrhage after mild traumatic brain injury in patients taking DOACs.

BACKGROUND: Although the preliminary evidence seems to confirm a lower incidence of post-traumatic bleeding in patients treated with direct oral anticoagulants (DOACs) compared to those on vitamin K antagonists (VKAs), the recommended management of mild traumatic brain injury (MTBI) in patients on DOACs is the same as those on the older VKAs, risking excessive use of CT in the emergency department (ED). AIM: To determine which easily identifiable clinical risk factors at the first medical evaluation in the ED may indicate an increased risk of post-traumatic intracranial haemorrhage (ICH) in patients on DOACs with MTBI. METHODS: Patients on DOACs who were evaluated in the ED for an MTBI from 2016 to 2020 at four centres in Northern Italy were considered. A decision tree analysis using the chi-square automatic interaction detection (CHAID) method was conducted to assess the risk of post-traumatic ICH after an MTBI. Known pre- and post-traumatic clinical risk factors that are easily identifiable at the first medical evaluation in the ED were used as input predictor variables. RESULTS: Among the 1146 patients on DOACs in this study, post-traumatic ICH was present in 6.5% (75/1146). Decision tree analysis using the CHAID method found post-traumatic TLOC, post-traumatic amnesia, major trauma dynamic, previous neurosurgery and evidence of trauma above the clavicles to be the strongest predictors associated with the presence of post-traumatic ICH in patients on DOACs. The absence of a concussion seems to indicate subgroups at very low risk of requiring neurosurgery. CONCLUSIONS: The machine-based CHAID model identified distinct prognostic groups of patients with distinct outcomes based on clinical factors. Decision trees can be useful as guides for patient selection and risk stratification.

Prevalence and management of antivitamin K overdose in a hospital setting.

INTRODUCTION: Vitamin K antagonist (VKA) related adverse events are the first cause for iatrogenic events in France, particularly due to the narrow therapeutic margin. The risk of bleeding increases significantly when the INR level is ≥5. The main objective of this study was to assess the prevalence of VKA overdose in a hospital setting (at D2 of hospital entry) and to evaluate physicians' adherence to clinical practice guidelines for the management of VKA overdose according to French National Authority for Health recommendations. METHODS: This single-center retrospective observational study consisted in querying the computerized database of a Parisian hospital on 21275INR determinations (3995 patients, 6813 hospital stays) performed between 2013 and 2018. RESULTS: An INR level ≥5 was noted during 350 (6%) of the hospital stays, in 331 patients (of whom 57% were women). The mean age of the patient population with an INR≥5 was 81.1 years. Infection, heart failure and renal failure were the most frequent acute medical conditions for hospital admission. Twenty-three patients (7%) had a bleeding complication, 11 of which were major bleeding complications. Older age was associated with the severity of bleeding complications. Fifteen in-hospital deaths (4%) were reported, not related to bleeding events. The management of VKA overdose did not comply with the recommendations in 43% of cases, in particular for the highest INRs (50% of noncompliance for an INR>6.4). Non-compliance with recommendations for VKA overdose was related to: the delay until the INR was checked (44% of cases); the indication for prescribing vitamin K (34% of cases); the dose or route of administration of vitamin K therapy (19% of cases); and the interruption or not of VKA therapy (12% of cases). CONCLUSION: The management of VKA overdose in a hospital setting remains non-compliant with the recommendations in almost half of the cases, mainly due to the delayed INR control and inappropriate management of vitamin K therapy. Computerized alert system would be helpful for personalized patient management and improved pharmacovigilance to prevent iatrogenic VKA events.

Cost-Effectiveness of Direct Non-Vitamin K Oral Anticoagulants Versus Vitamin K Antagonists for the Management of Patients with Non-Valvular Atrial Fibrillation Based on Available "Real-World" Evidence: The Italian National Health System Perspective.

BACKGROUND AND OBJECTIVE: The increasing availability of real-world evidence (RWE) about safety and effectiveness of direct non-vitamin K oral anticoagulants (DOACs) for the management of atrial fibrillation (AF) offers the opportunity to better understand the clinical and economic implications of DOACs versus vitamin K antagonists (VKAs). The objective of this study was to compare the economic implications of DOACs and VKAs using data from real-world evidence in patients with AF. METHODS: A Markov model simulating the lifetime course of patients diagnosed with non-valvular AF was used to evaluate the cost-effectiveness of DOACs (i.e., rivaroxaban, dabigatran and apixaban) versus VKAs from the Italian National Health System (INHS) perspective. The model was made up of data from the literature and a meta-analysis of RWE on the incidence of stroke/systemic embolism (SE), major bleeding (MB), intracranial haemorrhage (ICH) and all-cause mortality (ACM); direct costs included drug costs, costs for drug monitoring, and management of events from official national lists. One-way and probabilistic sensitivity analyses (PSA) were used to assess the robustness of the results. RESULTS: Results from the meta-analysis showed that apixaban had a high probability of being the most effective for stroke/SE, MB and ACM. Despite their higher acquisition costs, the cost-effectiveness analysis showed all DOACs involved a saving when compared with VKAs, with per-patient savings ranging between €4647 (rivaroxaban) to €6086 (apixaban). Moreover, all DOACs indicated a gain both in quality-adjusted life-years and life-years. According to PSA, findings related to apixaban were consistent, while for dabigatran and rivaroxaban PSA revealed a higher degree of uncertainty. CONCLUSIONS: The beneficial effect of DOACs on containing events showed in RWE had the potential to offset drug-related costs, thus improving the sustainability of treatment for non-valvular AF in daily clinical practice.

Health-related quality of life correlates with time in therapeutic range in children on anticoagulants with International Normalised Ratio self-monitoring.

BACKGROUND: Managing oral anticoagulant therapy with vitamin K antagonists remains challenging in paediatric medicine. AIMS: This study aimed to assess the correlation between time in therapeutic range and quality of life in children participating in a non-selective International Normalised Ratio self-monitoring and vitamin K antagonist education programme. METHODS: Children aged from 2 to 18 years and receiving vitamin K antagonist therapy were eligible for this prospective multicentre study. Clinical and demographic data were collected. Health-related quality of life was assessed using the PedsQL™ 4.0 questionnaire. Correlations between quality of life scores and time in therapeutic range were measured. RESULTS: A total of 121 children were included in the study (mean age 9.6±4.9 years). Cardiac conditions were the predominant indication for vitamin K antagonists. The mean time in therapeutic range was 0.78±0.15 overall, and 0.76±0.24 over the 3-month period before quality of life assessment. The mean total quality of life score was 76.2±18 in self reports, 71.4±22 in mother reports and 73.5±19 in father reports. The time in therapeutic range correlated with the total quality of life 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 time in therapeutic range predominantly correlated with school functioning in self reports (r=0.38; P=0.002) and mother reports (r=0.40; P<0.001), and with physical functioning in father reports (r=0.28; P=0.03). CONCLUSIONS: Time in therapeutic range correlated with quality of life in children participating in a non-selective International Normalised Ratio self-monitoring and vitamin K antagonist education programme. Regular assessment of quality of life in patient education programmes contributes towards understanding the concerns and needs of patients.

Cost-effectiveness of direct oral anticoagulants versus vitamin K antagonist in atrial fibrillation: A study protocol using Real-World Data from Catalonia (FantasTIC Study).

BACKGROUND: Anticoagulant therapy is used for stroke prevention and proved to be effective and safe in the long term. The study aims to analyse the cost-effectiveness relationship of using of direct-acting oral anticoagulants vs vitamin K antagonists to prevent ischaemic stroke in patients with nonvalvular atrial fibrillation, including all the active ingredients marketed in Spain, prescribed for 2 years in the Primary Care service of the Institut Català de la Salut. METHODS: Population-based cohort study, in which the cost of the 2 treatment groups will be evaluated. Direct costs (pharmacy, primary care, emergency and hospitalization) and indirect costs (lost productivity) will be included from a social perspective. Effectiveness (assessed as the occurrence of a health event, the 1 of primary interest being stroke) will be determined, with a 2-year time horizon and a 3% discount rate. The average cost of the 2 groups of drugs will be compared using a regression model to determine the factors with the greatest influence on determining costs. We will carry out a univariate ('one-way') deterministic sensitivity analysis. DISCUSSION: We hope to provide relevant information about direct and indirect costs of oral anticoagulants, which, together with aspects of effectiveness and safety, could help shape the consensual decision-making of evaluating bodies.

Satisfaction, quality of life and therapy adherence assessment in real life patients transitioning from vitamin K antagonists to direct oral anticoagulants.

Anticoagulant therapy has undergone a significant change since direct oral anticoagulants (DOACs) introduction. Their obvious advantages including the fixed dose, the few interactions and less frequent controls, have made them the first choice anticoagulant therapy. More and more patients have therefore switched from therapy with vitamin K antagonists (VKAs) to DOACs. Aim of our study was to assess the satisfaction, quality of life (QoL) and therapy adherence of patients who switched from VKA to DOACs therapy. This single center study evaluated satisfaction and QoL of 107 patients who switched from VKA to DOACs therapy through Anti-Clot Treatment Scale and SF-36 respectively. The questionnaires were administered before therapy change, after 3 months of DOACs therapy and then annually. We also evaluated DOACs therapy adherence with a questionnaire administered each visit and through the measures of DOACs plasma levels. Patients' satisfaction and QoL were high during VKA therapy, but with DOACs we observed an improvement after the first 3 months and then maintained over the time of DOACs therapy. DOACs adherence was excellent, also confirmed by DOACs plasma levels.

Current status and factors influencing oral anticoagulant therapy among patients with non-valvular atrial fibrillation in Jiangsu province, China: a multi-center, cross-sectional study.

BACKGROUND: It has been reported that oral anticoagulation (OAC) is underused among Chinese patients with non-valvular atrial fibrillation (NVAF). Non-vitamin K antagonist oral anticoagulants (NOAC) have been recommended by recent guidelines and have been covered since 2017 by the Chinese medical insurance; thus, the overall situation of anticoagulant therapy may change. The aim of this study was to explore the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province. METHODS: This was a multi-center, cross-sectional study that was conducted in seven hospitals from January to September in 2017. The demographic characteristics and medical history of the patients were collected by questionnaire and from the medical records. Multivariate logistic regression was used to identify factors associated with anticoagulant therapy. RESULTS: A total of 593 patients were included in the analysis. A total of 35.6% of the participants received OAC (11.1% NOAC and 24.5% warfarin). Of those patients with a high risk of stroke, 11.1% were on NOAC, 24.8% on warfarin, 30.6% on aspirin, and 33.6% were not on medication. Self-paying, duration of AF ≥5 years were negatively associated with anticoagulant therapy in all patients (OR 1.724, 95% CI 1.086~2.794; OR 1.471, 95% CI 1.006~2.149, respectively), whereas, permanent AF was positively associated with anticoagulant therapy (OR 0.424, 95% CI 0.215~0.839). Among patients with high risk of stroke, self-paying and increasing age were negatively associated with anticoagulant therapy (OR 2.305, 95% CI 1.186~4.478; OR 1.087, 95% CI 1.041~1.135, respectively). CONCLUSIONS: Anticoagulant therapy is positively associated with permanent AF and negatively associated with self-paying, duration of AF > 5 years. Furthermore, the current status of anticoagulant therapy among Chinese patients with NVAF in Jiangsu province does not appear optimistic. Therefore, further studies should focus on how to improve the rate of OAC use among NVAF patients. In addition, policy makers should pay attention to the economic situation of the patients with NVAF using NOAC. TRIAL REGISTRATION: 2,017,029. Registered 20 March 2017 (retrospectively registered).

Real-world cost-effectiveness of rivaroxaban compared with vitamin K antagonists in the context of stroke prevention in atrial fibrillation in France.

OBJECTIVE: The objective was to assess the real-world cost-effectiveness of rivaroxaban, versus vitamin K antagonists (VKAs), for stroke prevention in patients with atrial fibrillation (AF) from a French national health insurance perspective. METHODS: A Markov model was developed with a lifetime horizon and cycle length of 3 months. All inputs were drawn from real-world evidence (RWE) studies: data on baseline patient characteristics at model entry were obtained from a French RWE study, clinical event rates as well as persistence rates for the VKA treatment arm were estimated from a variety of RWE studies, and a meta-analysis provided comparative effectiveness for rivaroxaban compared to VKA. Model outcomes included costs (drug costs, clinical event costs, and VKA monitoring costs), quality-adjusted life-years (QALY) and life-years (LY) gained, incremental cost per QALY, and incremental cost per LY. Sensitivity analyses were performed to test the robustness of the model and to better understand the results drivers. RESULTS: In the base-case analysis, the incremental total cost was €714 and the total incremental QALYs and LYs were 0.12 and 0.16, respectively. The resulting incremental cost/QALY and incremental cost/LY were €6,006 and €4,586, respectively. The results were more sensitive to the inclusion of treatment-specific utility decrements and clinical event rates. CONCLUSIONS: Although there is no official willingness-to-pay threshold in France, these results suggest that rivaroxaban is likely to be cost-effective compared to VKA in French patients with AF from a national insurance perspective.

Cost-Effectiveness Analysis of Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Thai Patients With Non-Valvular Atrial Fibrillation.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have been recommended as preferred options for stroke prevention in patients with atrial fibrillation (AF) versus warfarin by guidelines worldwide. AIM: This study aimed to evaluate the cost-effectiveness of each NOAC in a Thai health care environment, a country with upper middle-income economies based on the World Bank's classification. METHOD: A lifetime Markov model was created from a Thai societal perspective. The model consisted of 19 health states separated into two cycles: event cycle and consequence cycle. The consequences of AF included in the model were ischaemic stroke, intracranial haemorrhage, extracranial haemorrhage, and myocardial infarction. All NOACs available in Thailand (dabigatran 150 mg and 110 mg twice daily; rivaroxaban 20 mg once daily; apixaban 5 mg twice daily; edoxaban 60 mg and 30 mg once daily) were assessed using warfarin with an international normalised ratio of 2-3 as the reference. Inputs were a combination of published literature and local data when available. A willingness-to-pay of 160,000 Thai baht (THB)/quality-adjusted life year (QALY) was used as the threshold of being cost-effective. Incremental cost-effectiveness ratios and cost-effectiveness acceptability curves were estimated. RESULTS: All NOACs were not cost-effective strategies for the Thai AF population. The ranking of incremental cost-effectiveness ratios from lowest to highest were apixaban 5 mg twice daily (THB 692,136 or US$21,862) followed by edoxaban 60 mg once daily (THB 911,772 or US$28,799), edoxaban 30 mg once daily (THB 913,749 or US$28,861), dabigatran 150 mg twice daily (THB 1,102,106 or US$34,811), dabigatran 110 mg twice daily (THB 1,195,347 or US$37,756), and rivaroxaban 20 mg once daily (THB 1,347,650 or US$42,566). Cost-effectiveness acceptability curve indicated that apixaban had the highest potential to be a cost-effective strategy versus other NOACs. CONCLUSIONS: Our findings indicated that all NOACs were not cost-effective in the Thai AF population. Of the NOACs, apixaban may be the most likely to be cost-effective. These data may be useful for policymakers to perform a comprehensive evaluation of these agents for formulary decision and pricing negotiation.

Four-year trends in oral anticoagulant use and declining rates of ischemic stroke among 194,030 atrial fibrillation patients drawn from a sample of 12 million people.

BACKGROUND: Administrative data were used to investigate changes in hospitalizations for atrial fibrillation (AF), AF-related stroke, and treatment patterns between 2012 and 2016. METHODS: From the 'Ricerca e Salute' database, a population- and patient-based repository involving >12 million inhabitants and linking demographics, prescriptions, and hospital discharge records, all patients discharged alive with a diagnosis of AF between 2012 and 2015 were followed for 1 year. RESULTS: A total of 194,030 AF patients were included. The number of AF cases increased ~10% over time, from 4.0 per 1,000 inhabitants in 2012 to 4.4 per 1,000 in 2015. At 1 year, hospitalizations for ischemic stroke decreased from 21.3 per 1,000 patients with AF in 2012-2013 to 14.7 per 1,000 in 2015-2016 (-31%, 95% CI -18 to -41). Over the same period, oral anticoagulant (OAC) use increased from 56.7% to 64.4% (+14%, 95% CI +8 to +26), vitamin K antagonist use decreased (from 55.9 to 36.7%; -34%, 95% CI -21 to -44), whereas direct OACs (DOACs) increased (from <1% in 2012 to 27.7% in 2015). Antiplatelet prescriptions fell from 42.6% in 2012 to 28.1% in 2015. Hospitalizations for major bleeds, mainly gastrointestinal, increased from 1.5‰ in 2012-2013 to 2.3‰ in 2015-2016, whereas hemorrhagic stroke admissions decreased from 6.5‰ to 4.1‰. CONCLUSIONS: There was a slight increase in the prevalence of AF between 2012 and 2015, whereas the overall use of antiplatelet agents decreased and that of OAC, particularly DOACs, increased. Over the same period, 1-year hospitalizations for ischemic stroke declined substantially, with a declining rate of hemorrhagic strokes.

[Effectiveness, safety and costs of stroke prevention in non-valvular auricular fibrillation. Study of cohorts matched by Propensity score]. / Efectividad, seguridad y costes de la prevención tromboembólica en fibrilación auricular. Estudio de cohortes apareado por Propensity score.

OBJECTIVE: To analyze the use, effectiveness, safety and costs of stroke prevention in non-valvular atrial fibrillation (AF) in patients initiating treatment with dabigatran or vitamin K antagonists (VKA). SETTING: Primary Care (PC) at the Catalan Health Institute (ICS) in Catalonia, during 2011-2013. PARTICIPANTS: Patients attended in ICS PC centres with a registered diagnosis of AF who initiate dabigatran or VKA. INTERVENTIONS: Not applicable MAIN MEASUREMENTS: Number of prescriptions and reimbursements of dabigatran and VKA, incidence of stroke and haemorrhages, incidence of mortatlity, number of sickness leave, and costs associated to all the previous variables. RESULTS: 14,930 patients were included; 94.6% initiated VKA and 5.4%, dabigatran. Dabigatran patients were younger and with less comorbidity. There were no statistically significant differences between VKA and dabigatran in the risk of stroke, haemorrhages or death. The costs associated to AF management were higher for PC visits in the VKA group, and higher for laboratory and pharmacy in the dabigatran group, although overall costs were not statistically different. CONCLUSIONS: Most patients initiated VKA. We found no differences between VKA and dabigatran in the risk of stroke, haemorrhages or mortality.

How Did We Get Here?: A Historical Review and Critical Analysis of Anticoagulation Therapy Following Mechanical Valve Replacement.

Managing severe valvular heart disease with mechanical valve replacement necessitates lifelong anticoagulation with a vitamin K antagonist. Optimal anticoagulation intensity for patients with mechanical valves remains uncertain; current recommendations are inconsistent across guideline bodies and largely based on expert opinion. In this review, we outline the history of anticoagulation therapy in patients with mechanical heart valves and critically evaluate current antithrombotic guidelines for these patients. We conclude that randomized trials evaluating optimal anticoagulation intensity in patients with mechanical valves are needed, and that future guidelines must better justify antithrombotic treatment recommendations.

Assessment of agreement and time in therapeutic range of capillary versus venous international normalised ratio in frail elderly people in a nursing home.

Vitamin K antagonists are widely used, yet have a slim therapeutic margin and high iatrogenicity. Patients are monitored through international normalised ratio (INR) by venipuncture, but coagulometers could measure INR by capillary puncture. This prospective study evaluated the clinical concordance of capillary INR versus venous INR in 31 nursing home patients. Concordance was good and mean time in therapeutic range (TTR) markedly increased. Capillary INR is thus reliable, could improve TTR and decrease iatrogenicity.

New oral anti-coagulants versus vitamin K antagonists in high thromboembolic risk patients.

BACKGROUND: Oral anticoagulant therapy (VKA) is nowadays the mainstay of treatment in primary and secondary stroke prevention in patients with atrial fibrillation. Given the limited risk-benefit ratio of vitamin K antagonists, pharmacological research has been directed towards the development of products that could overcome these limits, new oral anticoagulants were recently introduced: dabigatran, rivaroxaban, apixaban, and edoxaban. AIM: Scope of the present study was to examine patterns of use, effectiveness, safety and mean annual cost per patient of anticoagulant treatment for non-valvular AF in real clinical practice. METHODS: A retrospective observational cohort study, by using administrative databases (drugs, hospitalizations, clinical visits, lab tests, population registry), was conducted in the Local Health Unit (LHU) of Treviso, Italy, from January 1, 2012 to December 31, 2016. RESULTS: 5597 subjects were selected, 2171 of which satisfied all inclusion criteria. In particular 1355 patients were treated with VKA, 577 patients were treated with NOAC, and 239 patients were treated initially with VKA and subsequently switched to NOAC (switch group). NOAC treatment showed to be superior to VKA and this superiority was statistically significant on both end-points: patients in the NOAC group reported less cardiovascular events (9,9%) and less bleeding episodes (5,5%) versus VKA patients (14,6% and 11,4%; p<,0001 and p = 0,0049, respectively). The mean cost per patient per year was respectively € 1323,9 for patients treated with NOAC versus € 1003,3 for patients treated with VKA. Cost difference appears to be largely driven by drug cost (€ 767,9 for NOAC versus € 17,7 for VKA patients) and by specialist visits and laboratory tests (€ 318,4 for NOAC versus € 733,4 for VKA patients). CONCLUSION: In this retrospective real-world study treatment with NOAC showed to be associated with significant reductions of CV events and bleeding events compared to VKA use, albeit at a higher NHS' direct cost per patient/year, mainly due to higher drug therapy cost.

Venous thromboembolism 2011-2018 in Stockholm: a demographic study.

Venous thromboembolism (VTE) is an important cause of morbidity and mortality in Western countries. The incidence rate of VTE is estimated at 1-2 cases per 1000 annually. This study was a population-based cohort study of previously treatment naïve patients with a first occurrence of venous thromboembolism (VTE), using data from the administrative health data register of the Stockholm Region 2011-2018. Data on anticoagulant treatment was taken from the Swedish Prescribed Drug Register. We also analyzed all VTE events between 2011 and 2018. Altogether 14,849 naïve incident VTE cases were identified. In 2011 the majority of patients with a first episode of VTE were prescribed warfarin versus non-vitamin K antagonist oral anticoagulants (NOACs), 1144 versus 5. In contrast in 2018, the majority of patients were treated with NOACs, 1049 versus 59 treated with warfarin. Treatment with low molecular weight heparin only decreased from 814 to 683 patients. The frequency of all VTE events in the population increased over time from 1.88/1000 to 1.93/1000 (p = 0.072), and PE diagnoses increased from 0.69/1000 to 0.76/1000 (p = 0.003). In conclusion, during 2011-2018 there has been a shift of prescription of warfarin to a clear predominance of NOACs in the treatment of VTE in the Stockholm Region, in line with current recommendations. In the clinical situation, treatment has been simplified as monitoring of warfarin has decreased substantially. PE events increased during the time period in the population even if the increase was rather modest, while all VTE events did not increase significantly.

Factors associated to adequate time in therapeutic range with oral vitamin K antagonists in Tunisia.

INTRODUCTION:   The quality of chronic anticoagulation and predictor factors of poor anticoagulant control in patients under acenocoumarol were unknown in North Africa. METHODS: It is an observational study, carried out between November 2015 and November 30, 2016. The international normalized ratio (INR) values were prospectively obtained, and TTR was calculated using the Rosendaal method. RESULTS: Overall, 215 patients were included in this study, with a mean age of 63±0,8 years. The prevalence of poor anticoagulation control was 78.1%; 95% CI [72.2-83.2] (168 patients with TTR less than 65%). The median TTR with the Rosendaal method was 44.4%. After multivariate adjustment, variables significantly associated with adequate anticoagulation level were: history of ischemic stroke (Adjusted OR equal to 4.3, 95% CI: 1.4-12.9), associated prescription of antiplatelet therapy (Adjusted OR equal to 3.5, 95% CI: 1.1-11.2), daily prescribed dose of coumarins less than 6 mg (Adjusted OR equal to 6.4, 95% CI: 1.1- 36) and lower risk of bleeding assessed as HAS-BLED score (Adjusted OR: 0.5, 95% CI: 0.3-0.8). CONCLUSION: The quality of anticoagulation management with VKA among outpatients who received acenocoumarol was suboptimal. Strategies should be undertaken by clinicians and patients to improve the quality of anticoagulation, to address challenges to adverse cardiovascular outcomes in individuals treated with chronic anticoagulation.

Cost-effectiveness of apixaban for stroke prevention in non-valvular atrial fibrillation in Saudi Arabia.

BACKGROUND: Apixaban, an oral anticoagulant for stroke and systemic embolism prevention in non-valvular atrial fibrillation (NVAF), was superior to warfarin in prevention of stroke and systemic embolism, bleeding outcomes and mortality (ARISTOTLE trial), and substantially reduced stroke risk, with no significant increase in major or intracranial bleeding risk versus aspirin (AVERROES trial). OBJECTIVE: Estimate cost-effectiveness of apixaban versus other anticoagulants for NVAF treatment in Saudi Arabia. DESIGN: Lifetime Markov model. SETTING: A published model was adapted from the United Kingdom (UK) to the Saudi Arabia setting. PATIENTS AND METHODS: The model enabled pairwise comparisons of apixaban against other anticoagulants, aspirin, and aspirin+clopidogrel. Apart from warfarin and aspirin, comparisons were indirect. Subpopulations included vitamin K antagonist (VKA) suitable and unsuitable patients. Medication and physician visit costs were from published lists. A cost ratio (0.533), from comparison of UK and Saudi physician visit costs, was applied to UK model inputs to estimate local event costs. Background life expectancy was from Saudi life tables. Model structure, treatment comparators, patient characteristics, event rates, and utilities were unchanged. Costs and health benefits were discounted by 3.5% annually. MAIN OUTCOME MEASURE: Incremental cost-effectiveness ratio of cost per quality-adjusted life-year (QALY) gained. SAMPLE SIZE: Model cohort of 1000 NVAF patients, for VKA suitable and VKA unsuitable populations. RESULTS: Apixaban was dominant versus warfarin (VKA suitable) and rivaroxaban (VKA suitable and unsuitable). Compared against dabigatran (110mg, 150 mg, 110/150mg), the cost/QALY gained for apixaban was $5166, $11 143, $10 849 (VKA suitable) and $5 157, $14 424, $14 134 (VKA unsuitable), respectively. Cost/QALY for apixaban versus aspirin and aspirin+clopidogrel was $14 805 and $5784 (VKA suitable); and $10 564 and $4203 (VKA unsuitable), respectively. Sensitivity analyses demonstrated consistency of findings across varying inputs. CONCLUSIONS: Apixaban was found to be cost-effective for stroke prevention among Saudi NVAF patients, when assessed using a US$20 000 willingness-to-pay threshold. LIMITATIONS: Lack of robust local clinical, cost and utility data for model inputs. Lack of head-to-head clinical trial data for rivaroxaban, dabigatran, and clopidogrel plus aspirin comparators. CONFLICT OF INTEREST: Study was funded by Pfizer Inc. and Bristol Myers-Squibb. KO, RS, SAK and AAA received salaries from their respective employers, but did not receive direct financial compensation for participation in or authorship of this study.