[Proper use of oral anticoagulants in the elderly patient]. / Le bon usage des anticoagulants oraux chez le patient âgé.

Direct oral anticoagulants (DOACs) are tending to supplant antivitamin K inhibitors (VKAs) in their common indications, dominated in elderly patients by atrial fibrillation and venous thromboembolism. Nevertheless, it remains necessary to know how best to use VKAs for which there are still indications. It is also important not to assume that AODs can be prescribed without risk, while ignoring certain particularities in their handling, particularly in the most fragile patients with co-morbidities and multiple medications.

Apixaban for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation in France: The PAROS cross-sectional study of routine clinical practice.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs), including apixaban, are recommended for prevention of stroke and systemic embolism in non-valvular atrial fibrillation (NVAF). AIMS: To describe the characteristics of patients starting anticoagulant treatment, identify the characteristics associated with apixaban prescription, and describe apixaban use in France. METHODS: This was a non-interventional multicentre French study. Patients with NVAF (aged≥18 years) with anticoagulant treatment started in the preceding 3 months were evaluated in four groups (NOAC [apixaban, dabigatran or rivaroxaban] or vitamin K antagonist [VKA]). RESULTS: Data from 2027 patients were eligible for analysis. Mean age was 73.0±11.2 years, 56.6% were men and 80.2% were anticoagulant naïve. Stage≥4 chronic kidney disease was present in 2.2% of patients prescribed apixaban, none of those prescribed dabigatran or rivaroxaban, and 16.8% of those prescribed VKAs. The median CHA2DS2-VASc score was 3 for all three NOACs and 4 for VKAs; the median HAS-BLED score was≥3 for 2.5-5.9% of patients prescribed NOACs and 12.0% of those prescribed VKAs. Apixaban was more likely to be prescribed than other NOACs in older patients with higher bleeding risk and decreased renal function, and VKAs in patients with lower bleeding risk and better renal function. Patients received a reduced dose (5mg/day; 30.4% patients) or a full dose (10mg/day; 69.6% patients) of apixaban. Only 79.3% of patients prescribed apixaban had doses consistent with the summary of product characteristics; underdosing was more frequent than overdosing. Off-label use of apixaban was observed, mainly in elderly patients, despite normal renal function and weight. CONCLUSIONS: Initiation of apixaban versus NOACs was more common among patients with increased age, higher bleeding risk and decreased renal function, whereas initiation of apixaban versus VKAs was more common among patients with lower bleeding risk and better renal function.

[Educational and information needs of patients under vitamin K antagonist therapy]. / Quels besoins d'information et d'éducation des patients traités par les anti-vitamines K ?

BACKGROUND: Adverse events related to vitamin K antagonists (VKA) represent a major public health problem. Informative tools and educative program contributes to the reduction of iatrogenic risk. The purpose of our study is to assess representations and information needs of patients under VKA therapy in order to develop a suitable therapeutic education program. METHODS: Individual semi-structured interviews were conducted among both long term VKA therapy patient and patients initiating VKA. The thematic analysis allowed us to explore patient's speech qualitatively and semi-quantitatively. RESULTS: The main needs in information concerned the modalities of treatment (27.6%), side effects (24.1%), precautions and management of VKA treatment (24.1%). Origin of the disease (P=0.022) and drug mechanism of action (0.012) were specially asked about by patients initiating their treatment. CONCLUSION: Patients under VKA therapy reported needs for information on both their pathology and their anticoagulant therapy. The therapeutic education approach will enable us to adapt the educational tools and messages to the needs of patients under VKA therapy.

[Time in therapeutic range (TTR) and follow-up of patients on vitamin K antagonist: A cohort analysis]. / Utilité du TTR (temps passé dans la cible thérapeutique) dans le suivi des patients sous antivitamine K : analyse d'une cohorte de patients.

INTRODUCTION: Despite the increasing utilization of direct oral anticoagulant (DOAC) prescriptions, vitamin K antagonists (VKAs) remain the treatment of choice for treating and preventing thromboembolic events. The morbidity and mortality of VKAs are partly due to the difficulty of keeping the patient within the therapeutic range. For patients treated by VKA, time in therapeutic range (TTR) is a quality parameter of treatment, widely used in clinical trials but rarely by prescribers. It is well established that its use correlates with the risk of hemorrhage, thrombosis or mortality. We studied this parameter in a cohort of patients to evaluate the quality of their therapeutic follow-up and tried to identify risk factors for low TTR. METHODS: The study was made in collaboration with LaboSud Oc Biologie for a duration of 4 months. It included 3387 patients representing 2,4029 INR. We calculated the patients' TTR. The laboratory transmitted to us the sex and age of each patient and the VKA molecule used, the therapeutic range and the specialty of the prescriber. We then analyzed the odds ratio associated with these different factors. RESULTS: The mean TTR was 68%, close to the TTR recommended by scientific societies. Patient's sex was the only statistically correlated factor, with a worse equilibrium in females taking VKAs (OR=1.22, 95% CI: 1.06-1.39, P=0.00552). Many factors usually correlated with poor equilibrium under VKA have not been studied due to lack of information. CONCLUSION: Given the context of economic restriction and the TTR of our cohort close to the recommended 70%, there would be no benefit in terms of safety to prefer DOAC for the patients involved in this study. Regular monitoring of the individual patient's as well as the cohort's TTR should optimize the management of patients receiving VKAs.

[Direct oral anticoagulants (DOACS): A necessary focus]. / Anticoagulants oraux directs (AOD) : une mise au point nécessaire.

In 2008, we decided to enter the era of direct oral anticoagulants (DOACS). Was that the right decision to make? The answer will depend on how well we meet the conditions of proper use. This means avoiding underdosing and overdosing as well as understanding how DOACS were validated so that our prescriptions fulfill their role in the management of thrombotic disease.

[Assessing post-hospitalization therapeutic ranges in elderly patients treated for atrial fibrillation with vitamin k antagonists]. / Évaluation de l'équilibre des AVK après hospitalisation, chez des sujets âgés, traités pour une fibrillation atriale.

BACKGROUND: In France, anticoagulants are among the most recommended treatments for serious accidents, particularly among the elderly. OBJECTIVES: The purpose of this study was to evaluate the impact of practical and validated tools designed to reduce the negative effects of vitamin K antagonist (VKA) treatments by assessing patients before and after the tools were implemented. METHODS: An exhaustive before and after multi-centric cohort study was performed in the Agen territory. The follow-up period corresponded to the six-month period post-hospitalization. The principal criterion was the time in the therapeutic range (TTR) at values of 2 to 3 according to the Rosendaal method. RESULTS: The overall time spent in the follow-up period before and after the implementation of the tools in 65- and 74-year-old patients was 58% and 64%, respectively (P=0.584). After the treatments, the TTR in the 85- to 90-year-old patients was 71.1%. An increase was observed in the number of subjects with a TTR≥70% after the implementation of the tools according to age, particularly in the 85- to 90-year-old patients (8 vs. 41; [P=0.01]). Prescription help software revealed a tendency of improvement in TTR values from 61% to 68% (P=0.472). In addition, longer therapeutic periods corresponded to longer patient lifespans (r=0.86). CONCLUSION: This study demonstrates the feasibility and advantages of implementing tools to improve the efficacy of VKA treatment in primary care, particularly for patients from 85 to 90 years old. The results should promote the implementation of this type of treatment method at the national level.

[Resistance to vitamin K antagonist revealing interaction with soy lecithin]. / Résistance aux antivitamines K révélant une interaction avec la lécithine de soja.

Vitamin K antagonists (VKA) are difficult to use because of a narrow therapeutic index and of a marked inter- and intra-individual variability among patients in the required dosage. This drug may interact with many other drugs and same with certain food compounds. We report the case of potential interaction between soy lecithin and Vitamin K antagonists in a 46 years-old woman. Subtherapeutic INR values were detected despite the increase gradually in dose and replacing acenocoumarol by fluindione. An enquiry of pharmacovigilance was conducted found the consumption of soy lecithin capsules. Fifteen days after its stopping, the INR values have really increased. Clinicians should think to the possibility of interaction between oral anticoagulants and food supplement that is increasingly used.

[Vitamin K antagonist-induced necrotic leg ulcer, without protein C and S deficiencies]. / Ulcères nécrotiques sous antivitamine K, sans déficit en protéine C et S associé.

INTRODUCTION: Patients treated by vitamin K antagonists (VKA) represent 1% of the population in France. We report a case of atypical necrotic leg ulcers induced by VKA. CASE REPORT: A 84-year-old woman was referred to our dermatology department because of necrotic leg ulcers that developed for the past 5weeks, and appeared spontaneously after the introduction of a VKA, fluindione. The etiological assessment was non contributive, in particular the search for thrombophilic factors. The skin biopsy found an aspect compatible with pyoderma gangrenosum. The outcome was favorable after discontinuing the fluindione and the switch to apixaban. A complete healing was obtained in 5months. CONCLUSION: We report an original case of necrotic leg ulcers induced by VKA without deficit of protein C or S, with a pyoderma like histology. Reported cases of ulcers induced by VKA are uncommon and the physiopathology is not well known. The involvement of VKA should be evoked in case of necrotic leg ulcer without specific etiology found.

Quality of life and patient satisfaction in patients with atrial fibrillation on stable vitamin K antagonist treatment or switched to a non-vitamin K antagonist oral anticoagulant during a 1-year follow-up: A PREFER in AF Registry substudy.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are being introduced for stroke prevention in non-valvular Atrial Fibrillation (AF), and promise to be accepted better than Vitamin K Antagonists (VKAs) by patients, improving their Quality of Life (QoL). AIM: To assess to what extent patient-related factors influence decisions to switch from a VKA to a NOAC. METHODS: The PREFER in AF Registry collected data at baseline in 2012 - at the beginning of NOAC prescriptions - and at 1-year follow-up, in 6412 patients in seven Western European countries. QoL and patient satisfaction questionnaires (EQ-5D-5L and/or PACT-Q2) were completed in 3777 patients at both visits. Data were compared across categories of patients on stable treatment with a VKA (i.e. continuously over the previous 12 months) (n=2102) or recently switched (within 12 months) from a VKA to a NOAC (n=213) during a 1-year follow-up, allowing a snapshot of factors influencing the switch at a time when NOACs were being introduced into the market. RESULTS: Compared to patients on stable treatment with a VKA, switched patients were similar in terms of age, sex, body mass index and other risk factors, but had lower prevalences of hypertension and heart valve dysfunction, and a lower rate of use of concomitant treatment with antiplatelet/anti-inflammatory agents; they also had a lower CHA2DS2-VASc score. Among 25 features investigated, switched patients more often reported bruising or bleeding, complained about bruising, were dissatisfied with the anticoagulant treatment, and reported mobility problems and anxiety/depressive traits. CONCLUSIONS: At the beginning of NOAC prescriptions, European doctors tended to switch from VKAs to NOACs those patients at lower risk than "non-switchers". Complaints about bruising or bleeding, dissatisfaction with treatment, mobility problems and anxiety/depression traits appear to be related to - and may have influenced - the choice to switch from a VKA to a NOAC.

[Retrospective study of hypertensive leg ulcers at Reims University Hospital: Epidemiological, clinical, disease progression data, effects of vitamin K antagonists]. / Étude rétrospective des angiodermites nécrotiques au CHU de Reims : données épidémiologiques, cliniques, évolutives et rôle des antivitamine K.

BACKGROUND: Hypertensive leg ulcers (HLU) are a form of necrotic leg ulcer. Their physiopathology is not well known and in these patients, no venous or arterial insufficiency is detected. The primary objective of this study was to evaluate the association between HLU severity and the presence or absence of concomitant vitamin K antagonist (VKA) medication. We furthermore aimed to describe the epidemiology of this entity and the prevalence of thrombophilia factors in this population. PATIENTS AND METHODS: This was a retrospective study in 54 patients hospitalized in the dermatology department of Reims University Hospital between 01/01/2007 and 31/12/2013: 23 patients were included in the "without VKA" group, and 30 were included in the "with VKA" group. Clinical and laboratory data were collected. RESULTS: The average HLU surface was higher in the "with VKA" group i.e. 35.00cm2 (min: 3.0; max: 220.0) versus 23.00cm2 (min: 5.0; max: 300.0) (P=0.05). No significant difference was found in terms of time to healing, mean hospitalization duration, HLU treatment by skin grafting, or time to recurrence after healing. Mean patient age was 74.2±9.3 years; 100% of patients had arterial hypertension, 50.9% had diabetes, and 20.8% were active smokers. Abnormal but non-significant values for thrombophilia factors were observed. CONCLUSION: Our study shows no obvious differences between patients with HLU with or without VKA medication. A prospective, comparative study is necessary to further evaluate this hypothesis, with particular emphasis on routine thrombophilia factor analysis.

[Vitamin K antagonist, direct oral anticoagulants: Where is the truth?] / Antivitaminiques K, anticoagulants oraux directs : où est la vérité ?

Vitamin K antagonists (VKA) and direct oral anticoagulants (DOACs) are now in competition. The companies are trying to replace VKA by DOACs, totally or at least greatly VKA should VKA disappear in favor of DOACs? There are still many questions about DOACs. The purpose of this article is to make a well-considered decision in this area. The aim is not to denigrate one or the other but to share things between these two families of anticoagulants. Physicians using these drugs must have a full knowledge about compared efficacy and safety. We feel necessary to increase distance between effective results of the clinical trials and industrial communication around DOACs.

Non-vitamin K antagonist oral anticoagulants and heart failure.

Thromboembolism contributes to morbidity and mortality in patients with heart failure (HF), and atrial fibrillation (AF) is one of the main factors promoting this complication. As they share many risk factors, HF and AF frequently coexist, and patients with both conditions are at a particularly high risk of thromboembolism. Non-vitamin K antagonist oral anticoagulants (NOACs) are direct antagonists of thrombin (dabigatran) and factor Xa (rivaroxaban, apixaban and edoxaban), and were designed to overcome the limitations of vitamin K antagonists. Compared with warfarin in non-valvular AF, NOACs demonstrated non-inferiority with better safety, most particularly for intracranial haemorrhages. Therefore, the European Society of Cardiology guidelines recommend NOACs for most patients with non-valvular AF. Subgroups of patients with both AF and HF from the pivotal studies investigating the safety and efficacy of NOACs have been analysed and, for each NOAC, results were similar to those of the total analysis population. A recent meta-analysis of these subgroups has confirmed the better efficacy and safety of NOACs in patients with AF and HF - particularly the 41% decrease in the incidence of intracranial haemorrhages. The prothrombotic state associated with HF suggests that patients with HF in sinus rhythm could also benefit from treatment with NOACs. However, in the absence of clinical trial data supporting this indication, current guidelines do not recommend anticoagulant treatment of patients with HF in sinus rhythm. In conclusion, recent analyses of pivotal studies support the use of NOACs in accordance with their indications in HF patients with non-valvular AF.

[Necrotic leg ulcer revealing vasculitis induced by vitamin K antagonists]. / Ulcère de jambe nécrotique révélant une vasculite induite par les antivitamines K.

UNLABELLED: Vitamin K antagonists are widely used in thromboembolic diseases. Hemorrhagic complications related to drug overdose represent their main side effect. We report a rare side effect, a severe and unexpected type of skin vasculitis - necrotic leg ulcer - induced by vitamin K antagonist. CASE REPORT: A 63-year-old female with a history of diabetes developed hyperalgesic necrotic ulcerations on the lower limbs one month after starting an acenocoumarol-based treatment for ischemic heart disease. Histological examination revealed lymphocytic vasculitis with fibrinoid necrosis. Etiological explorations searching for vasculitis were negative. In the absence of a precise etiology, drug-induced ulcer was suspected. Low molecular weight heparin was prescribed to replace acenocoumarol. The lesions slowly resolved with topical treatment. DISCUSSION: The chronological criteria and the negativity of etiological explorations allowed the diagnosis of vitamin K antagonist-induced necrotic skin ulcer. Clinicians should be aware of this rare complication induced by oral anticoagulants because of its practical therapeutic implications. This is the first case of necrotic leg ulcer induced by acenocoumarol corresponding histologically to necrotising lymphocytic vasculitis.

[Anticoagulation in atrial fibrillation in the elderly: the geriatrician point of view with a focus on the direct oral anticoagulants]. / L'anticoagulation dans la fibrillation atriale du sujet âgé : point de vue du gériatre avec un focus sur les anticoagulants oraux directs.

Prescribing anticoagulant therapy when the CHA2DS2-VASc score is ≥ 1 prevents strokes secondary to non-valvular atrial fibrillation (AF). However, it is important to remember that whether the aged population has the highest risk of stroke in case of AF, under anticoagulant therapy this population is also at the highest risk of bleeding. Vitamin K antagonists were for decades the molecules of reference with benefits even after 75 years of age. The direct oral anticoagulants have overcome the biological constraints inherent to monitoring vitamin K antagonists and provide a more stable pharmacological action with a limited number of drug-drug interactions. However, the widespread use of these molecules in the older population remains controversial. In this review article, indications and modalities of administration of anticoagulant therapy in the elderly will be detailed and discussed on the basis of the most recent recommendations proposed in particular by the European Society of Cardiology. Particular attention will be paid to new oral anticoagulant therapies compared with vitamin K antagonists and antiplatelet agents.

[Relationship between maintenance dosages of fluindione (Préviscan) and warfarin (Coumadin) for patients 70 years and older]. / Nomogramme d'équivalence entre les posologies de fluindione (Préviscan) et de warfarine (Coumadine) pour des patients de 70 ans et plus.

INTRODUCTION: Switching from fluindione, an indanedione vitamin K antagonist derivative, to warfarin, a coumarin one, or vice versa, requires to know the relationships between dosages of these two molecules. METHODS: We conducted a prospective study in 288 consecutive patients aged 70 years and over, converted from fluindione to warfarin. Patients who were retained for the analysis were those for whom maintenance dosages were obtained for both vitamin K antagonists. RESULTS: Eighty-two patients, mean aged 83 ± 6 years, were analysed. The average daily maintenance dosages were 13.8 ± 6.7 mg (range 5-35) and 3.7 ± 1.7 mg (range 1-8) for fluindione and warfarin, respectively. Using a linear regression model, we built a transition algorithm for the maintenance dosages of warfarin and fluindione. CONCLUSION: This is the first study to propose a conversion algorithm to help prescribers to estimate the maintenance dosage when it is necessary for a patient to switch from fluindione to warfarin or conversely.

[Risk factors of serious bleeding among ambulatory patients taking antivitamin K aged 75 and over]. / Les déterminants d'hémorragies graves des sujets ambulatoires âgés de 75ans et plus sous antivitamine K.

The benefits of anti-vitamin K (AVK) drugs have been acknowledged in several indications. Such indications increasing with increasing age, AVK prescriptions also increases with age. At the same time, conditions involving significant bleeding are common in this elderly population. It is thus essential to recognize the determining factors. This study included all patients taking AVK drugs aged 75 years and older who sought emergency care at the Cochin Hospital from January to December 2011 for significant bleeding. These patients were compared with a cohort of patients aged 75 years or older who were taking AVK drugs and who were admitted to the same unit during the same time period for other reasons. The case-control comparison included demographic data, comorbidity factors, multiple medications, emergency measured INR, and CHA2DS2VASC level. The hemorrhagic risk was evaluated by HEMORR2HAGES and HAS-BLED. A total of 34 patients were studied and compared with 70 case-controls. The Charlson comorbidity index was higher in patients than case-controls (P<0.05), with a much higher hemorrhagic risk for scores ≥ 9 (OR=2.5; P<0.05). Multiple medication was also more predominant in patients (P<0.05). The risk of serious hemorrhage was also higher when the hemorrhagic scores were high, especially for HEMORR2HAGES (P<0.0001) and HAS-BLED (P<0.001). The risk of serious hemorrhage in elderly outpatients taking AVK drugs is related to their higher comorbidity and hemorrhagic levels which need to be evaluated before starting or stopping AVK treatment.