Vitamin K Antagonists Treatment Research Articles

Antithrombotics in pulmonary hypertension: more work needed before we turn to newer agents!

Therapeutic research is particularly dynamic in the setting of pulmonary arterial hypertension (PAH). Despite the low prevalence of this rare disease, the efficacy and safety of targeted PAH therapies have been evaluated in randomised controlled trials, providing important data for clinicians, health authorities and patients. Beside these well-studied targeted therapies, “supportive therapy” is also recommended. This includes antithrombotic therapy with vitamin-K antagonists (VKAs) [1]. The background for the use of these agents is principally supported by findings in histopathological and biological studies [2, 3], as well as their potential indirect clinical consequences which may present as perfusion defects evaluated by ventilation/perfusion ( V ′/ Q ′) scan [4]. Clinical studies evaluating VKAs in the setting of PAH are, however, lacking. In the prospective study published by Rich et al. [5], VKA use improved prognosis, but the allocation to VKA treatment followed the demonstration of perfusion defects on V ′/ Q ′ scan, and not from proper randomisation. This explains the low level of the related recommendation in the guidelines from the European Respiratory Society and European Society of Cardiology [1], that being a class IIa recommendation for idiopathic or heritable PAH and for PAH due to anorexigens, and an even lower level of recommendation in patients with associated PAH. By extension, anticoagulant therapy has been proposed in other groups of pulmonary hypertension (groups 2, 3 or 5) despite the absence of specific studies. Paradoxically, whereas only half of patients with a certain indication for VKA therapy (for example, atrial fibrillation) receive VKA [6], most PAH patients are anticoagulated with VKA (90% of the patients included in the French registry) [7]. Conversely, antithrombotic therapy with VKA is the cornerstone of medical therapy in the case of …

Statin treatment and the risk of recurrent pulmonary embolism

Patients with idiopathic venous thromboembolism (VTE) have a high recurrence risk during and after stopping anticoagulant treatment. Several studies suggest that treatment with statins reduces the incidence of a first episode of VTE, but data on the effects in patients with a previous episode are lacking. We examined the effect of statin therapy on the risk of recurrent pulmonary embolism (PE). Using the PHARMO Record Linkage System, a Dutch population-based registry of pharmacy records linked with hospital discharge records, patients hospitalized with an acute episode of PE were identified between 1998 and 2008. Prescription-based use of statins and vitamin K antagonist (VKA) were identified starting at hospital discharge and during follow-up. The association between statin use (time-varying) and the incidence of recurrences, cardiovascular events, and death was assessed using Cox regression analysis. The mean (standard deviation) age was 61 (17) years. The median (range) duration of VKA treatment after acute PE was 199 (45-3793) days. Twenty-four per cent of the patients (n = 737) had at least one prescription of statins during the follow-up period and the median duration of statin therapy was 1557 (5-4055) days. During a median follow-up of 1529 (1-4155) days, 285 (9.2%) patients experienced a recurrence. Treatment with statins was associated with a reduced risk of recurrent PE [adjusted hazard ratio (HR) 0.50, 95% CI: 0.36-0.70], both during and after stopping VKA treatment. A dose-response relationship was shown for potency, with the largest reduction in those with the most potent statins. Finally, statin treatment also reduced the risk for cardiovascular events and all-cause mortality. Statin treatment decreases the risk of recurrent PE, irrespective of VKA treatment. Treatment with statins may be an attractive alternative for anticoagulant treatment in the long-term treatment of PE.

Cessation of oral anticoagulation in relation to mortality and the risk of thrombotic events in patients with atrial fibrillation

Bleeding risk (often perceived, rather than actual) is a common reason for cessation of oral anticoagulation with Vitamin K antagonists (VKA). We investigate clinical outcomes in a consecutive population of VKA naïve atrial fibrillation (AF) patients, who initiated VKA therapy in our clinic. We included consecutive VKA-naïve patients with non valvular AF, initiated on VKA therapy in our anticoagulation outpatient clinic in 2009. During follow-up, adverse events [thrombotic/vascular events (stroke, acute coronary syndrome, acute heart failure and cardiac death), major bleeding and death], and VKA cessation were recorded. At the end of the follow-up, we determined time within therapeutic range (TTR), using a linear approximation (Rosendaal method). We studied 529 patients (49% male, median age 76), median follow-up 835 days (IQR 719-954). During this period 114 patients stopped VKA treatment. 63 patients suffered a thrombotic/cardiovascular event (5.17%/year, 27 thrombotic/ischaemic strokes), 51 major bleeding (4.19%/year) and 48 died (3.94%/year). Median TTR was 54% (34-57). On multivariate analysis (adjusted by CHA₂DS₂-VASc score), VKA cessation was associated with death [Hazard Ratio (HR) 3.43; p<0.001], stroke [4.21; p=0.001] and thrombotic/cardiovascular events [2.72; p<0.001]. Independent risk factors for major bleeding were age [1.08; p<0.001], previous stroke [1.85; p=0.049], and TTR [0.97; p=0.001], but not VKA cessation. In conclusion, in AF patients AF, VKA cessation is independently associated with mortality stroke and cardiovascular events. Specifically, VKA cessation independently increased the risk of stroke, even after adjusting for CHA₂DS₂-VASc score. TTR was an independent risk factor for major bleeding following initiation of VKA therapy.

289: Vitamin K antagonists self management with COAGUCHEK XS® in children: an observational study

The use of COAGUCHEK XS ® (Roche Diagnostics), an INR home measuring device, was authorised by the French Health High Authority on June 2008 for children. Nevertheless, there are few data on safety and effectiveness of patients self management particularly in children. Since 2008, 23 children (mean age: 9 y; 16 males, 7 females) and their families were trained to INR self testing and self management of vitamin K antagonists (VKA) (acenocoumarol: n=10, fluindione : n=9, warfarin: n=4). INR controls (self testing or lab) were made at expected dates established by the french law. Additional measurements were authorised in risky situations (illness, hyperthermia, forgetting VKA treatment, bleeding, etc…). Drug dose adaptation was made either by the family or by the health team if needed. To evaluate safety and efficacy in families performing self management in our centre. Time in therapeutic range (TTR), severe haemorrhage (needing hospitalization and/or blood transfusion) and thrombosis recurrence were observed. Mean follow-up time was 529 days [1.5 y; range 0.3-2.5y]. Mean TTR was 68.53% and was 90.14% when tolerance range was applied. There was no severe haemorrhage or thrombosis recurrence during follow-up and INR >5 were 0.5% (8/1604 measurements). Lastly, 3.5% additional measurements were performed by the families. VKA self management using COAGUCHEK XS ® was safe and effective in our centre. Clinical studies with larger sample and cost-effectiveness considerations are required.

Abstract 18238: Transition from Vitamin-K-antagonists to New Oral Anticoagulants in Daily Care - First Results of the Prospective NOAC Registry (NCT 01588119)

Background: New oral anticoagulants (NOAC) have been approved in a number of countries for long-term anticoagulation in atrial fibrillation (AF) and venous thromboembolism (VTE). Currently, many patients are switched from Vitamin-K antagonists (VKA) to NOAC. We evaluated the transition process (time gap between last intake of VKA, last INR sampling and first intake of NOAC) in unselected patients from daily care. Patients and methods: A network of 115 physicians from private practice and hospitals enrol patients in the NOAC registry. Inclusion criteria are: 1) indication for NOAC anticoagulation &gt;3 month; 2) age &gt; 18 years; 3) written informed consent; 4) availability for follow-up. No Exclusion criteria apply. Patients are prospectively followed by phone visits at day 30 day and quarterly thereafter to collect efficacy and safety data. Results: Until June 6 th 2012, 683 patients were registered. Of the 266 patients switched from VKA, data on the transition process were available in 213 patients (70.0% AF, 30.0% VTE). Of these, only 104 patients (48.8%) had a recorded INR measurement at the end or within 7 days before the end of VKA treatment (mean INR 2.4 for all, 2.6 in AF and 2.1 in VTE patients; table 1). In patients with INR tests, time between last INR and start of NOAC was around 3 days (5 days in AF and 2 days in VTE patients). For all patients, time between last VKA and start NOAC was around 7 days (8 days in AF; 4 days in VTE patients). Conclusion: In unselected patients in daily care, only 50% of patients have a documented INR test before NOAC is started. Despite documented INR values in the lower therapeutic range, physicians are reluctant to start NOAC therapy immediately and allow for another 2 to 5 days before NOAC is started. However, no major vascular events or major bleedings were observed in VKA transition patients at day 30, indicating that this procedure is safe.

Cancer risk in long‐term users of vitamin K antagonists: A population‐based case–control study

Some evidence suggests that long-term use of vitamin K antagonists (VKAs) has a cancer chemopreventive effect. Such an effect would have considerable implications in terms of understanding tumor biology. To evaluate if long-term VKA treatment influences the risk of developing cancer, we performed a matched case-control analysis. We used data from four Danish nationwide registers. Cases were all Danish individuals with a first-time cancer diagnosis (except nonmelanoma skin cancer) between 2000 and 2009. For each case, eight controls, matched by birth year and gender, were selected from the source population by risk-set sampling. Long-term VKA use was defined as exposure to VKA for a period of 3 or more years. Conditional logistic regression was used to compute odds ratios (ORs) for cancer associated with long-term VKA exposure, adjusting for potential confounders. Prespecified subanalyses were performed for selected cancer sites, subgroups and measures of exposure. A total of 238,196 cases and 1,713,176 controls were included. The adjusted OR for cancer associated with long-term VKA exposure was 0.99 (95% CI: 0.95-1.02). Long-term VKA use was associated with increased ORs for alcohol- or obesity-related cancer sites, whereas we observed a decreased risk of prostate cancer (OR: 0.86; 95% CI: 0.78-0.95). Our study does not support a general chemopreventive effect of VKA drugs. However, in accordance with findings from previous studies, we found an inverse association between use of VKA and prostate cancer.

Secondary Intracerebral Hemorrhage Due to Early Initiation of Oral Anticoagulation After Ischemic Stroke

The uncertain risk of secondary intracerebral hemorrhage (sICH) frequently keeps clinicians from initiating oral anticoagulation (OAC) early after ischemic cardioembolic stroke. The goal of this experimental study was to determine the risk of sICH depending on the timing of OAC initiation relative to stroke onset and to address the role of hematogenous macrophages for repair processes preventing OAC-associated sICH. C57BL/6 mice were subjected to transient middle cerebral artery occlusion. Subgroups were treated with either the vitamin K antagonist (VKA) phenprocoumon or the direct thrombin inhibitor dabigatran etexilate. Hematogenous macrophages were depleted using intraperitoneal injections of clodronate-filled liposomes. Time to therapeutic OAC was 48 hours with VKA and 0.5 hours with dabigatran etexilate treatment. In VKA-treated mice, the risk of sICH was high if effective OAC was already present at stroke onset or achieved within 48 hours after ischemia. With more delayed OAC, the risk of sICH rapidly decreased. Compared with VKA treatment, effective anticoagulation with dabigatran etexilate was associated with a significantly reduced extent of sICH, either if present at stroke onset or if achieved 48 hours later. Partial depletion of macrophages greatly increased the extent of OAC-associated sICH in the subacute stage of 3 to 4 days after ischemia. Our findings suggest that repair mechanisms involving hematogenous macrophages rapidly decrease the risk of OAC-associated sICH in the first days after ischemic stroke. The lower risk of sICH under dabigatran etexilate compared with VKA treatment may facilitate early initiation of OAC after cardioembolic stroke.

Bleeding During Treatment With Aspirin Versus Apixaban in Patients With Atrial Fibrillation Unsuitable for Warfarin

Apixaban reduces stroke with comparable bleeding risks when compared with aspirin in patients with atrial fibrillation who are unsuitable for vitamin k antagonist therapy. This analysis explores patterns of bleeding and defines bleeding risks based on stroke risk with apixaban and aspirin. The Apixaban versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin k Antagonist Treatment (AVERROES) trial randomized 5599 patients with atrial fibrillation and risk factors to receive either apixaban or aspirin. Bleeding events were defined as the first occurrence of either major bleeding or clinically relevant nonmajor bleeding. The rate of a bleeding event was 3.8%/year with aspirin and 4.5%/year with apixaban (hazard ratio with apixaban, 1.18; 95% CI, 0.92-1.51; P=0.19). The anatomic site of bleeding did not differ between therapies. Risk factors for bleeding common to apixaban and aspirin were use of nonstudy aspirin>50% of the time and a history of daily/occasional nosebleeds. The rates of both stroke and bleeding increased with higher CHADS2 scores but apixaban compared with aspirin was associated with a similar relative risk of bleeding (P interaction 0.21) and a reduced relative risk of stroke (P interaction 0.37) irrespective of CHADS2 category. Anatomic sites and predictors of bleeding are similar for apixaban and aspirin in these patients. Higher CHADS2 scores are associated with increasing rates of bleeding and stroke, but the balance between risks and benefits of apixaban compared with aspirin is favorable irrespective of baseline stroke risk. Clinical Trial Registration Information- www.clinicaltrials.gov. Unique identifier: NCT 00496769.

Benchmark for Time in Therapeutic Range in Venous Thromboembolism: A Systematic Review and Meta-Analysis

IntroductionThe percentage of time within the target INR range 2.0 to 3.0 (TTR) in patients treated with vitamin K antagonists varies considerably among efficacy-studies of novel anticoagulants. In order to properly asses the quality of anticoagulant control in upcoming cost-effectiveness studies and real life registries this systematic review reports a benchmark of TTR for different treatment durations in patients with venous thromboembolism and discusses ways to calculate TTR.MethodsMedline and Embase were searched for studies published between January 1990 and May 2012. Randomized controlled trials and cohort studies reporting the TTR in patients with objectively confirmed venous thromboembolism treated with vitamin K antagonists (VKA) were eligible. Duplicate reports, studies only reporting INR during initial treatment or with VKA treatment less than 3 months were excluded. Three authors assessed trials for inclusion and extracted data independently. Discrepancies were resolved by discussion between the reviewers. A meta-analysis was performed by calculating a weighted mean, based on the number of participants in each included study, for each time-period in which the TTR was measured since the confirmation of the diagnosis of VTE.ResultsForty studies were included (26064 patients). The weighted means of TTR were 54.0% in the first month since the start of treatment, 55.6% in months 1 to 3, 60.0% in months 2 to 3, 60.0% in the months1 to 6+ and 75.2% in months 4 to 12+. Five studies reported TTR in classes. The INR in these studies was ≥67% of time in therapeutic range in 72.0% of the patients.ConclusionReported quality of VKA treatment is highly dependent on the time-period since the start of treatment, with TTR ranging from approximately 56% in studies including the 1st month to 75% in studies excluding the first 3 months.

Cost-Effectiveness of Apixaban Compared With Aspirin for Stroke Prevention in Atrial Fibrillation Among Patients Unsuitable for Warfarin

Compared with aspirin, apixaban reduces stroke risk in atrial fibrillation (AF) patients unsuitable for warfarin by 63% but does not increase major bleeding. We sought to determine the cost-effectiveness of apixaban versus aspirin. Using the Apixaban versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin-K Antagonist Treatment (AVERROES) trial and other studies, we constructed a Markov model to evaluate the costs (2011US$), quality-adjusted life-years (QALYs), and incremental cost-effectiveness of apixaban versus aspirin from the Medicare perspective. Our base-case assumed a 70-year-old AF patient cohort with a CHADS(2) score=2 and a lower-risk of bleeding. We used a 1-month cycle-length and ran separate base-case analyses assuming a trial-length (1-year) and a longer-term (10-year) follow-up. Total costs/patient were $3454 and $1805 for apixaban and aspirin in the trial-length and $44 232 and $50 066 in the 10-year model. Corresponding QALYs were 0.96 and 0.96 in the trial-length and 6.87 and 6.51 in the 10-year model, making apixaban inferior in the first model but dominant in the latter. Conclusions were sensitive to baseline stroke rate in both models, and the monthly cost of major stroke, relative risk of stroke, and prior vitamin-K antagonist use in the life-time model. Probabilistic sensitivity analysis suggested apixaban would only be a cost-effective alternative (<$50 000/QALY) to aspirin 11% of the time in the trial-length model, but cost-effective or dominant 96.7% and 87.5% of iterations in the 10-year model. In our trial-length model, apixaban was more costly and no more effective than aspirin; however, as follow-up was extended, apixaban became cost-effective and eventually dominant.

Portable Technologies for Self-Monitoring of Coagulation Time: A Review

Anti-coagulation treatments are required for medical conditions that become more and more frequent with the ageing of the population in developed countries (atrial fibrillation, deep-venous thrombosis, heart prosthetic valves, etc.). These treatments generally use coumarin derivative (vitamin-K antagonist), whose activity needs to be monitored in order to keep the patient in an appropriate therapeutic range. This measurement can be done in laboratories but can also be performed by the patient himself using portable devices. This paper presents the different technological ways to selfmonitor vitamin-K antagonist treatment by measuring coagulation time. It will focus on portable devices, well suited to be used at home and on device to be manipulated by the patient, thus not requiring an extensive training nor sample treatment. Keywords: Anti-coagulant, vitamin-K antagonist, coagulation, coagulation time measurement, coumarin, diagnostic, hand-held devices, international normalized ratio, point-of-care, portable devices, prothrombin time, Quick test, self-monitoring, thromboses prevention.

Abstract 170: Pharmacological Stroke Prophylaxis and Correlates among Patients with Atrial Fibrillation: The US National Health and Wellness Survey

Purpose: To describe pharmacological stroke prophylaxis and identify patient characteristics associated with vitamin K antagonist (VKA) and/or aspirin (ASA) use among adult patients with atrial fibrillation (AF). Methods: Data were analyzed from the 2009 U.S. National Health and Wellness Survey, a self-administered, internet-based epidemiological study of a nationwide sample of 75,000 adults (aged 18+) stratified by gender, age, and race/ethnicity. Included were a total of 1,290 participants (1.72%) who checked AF diagnosis among their condition(s) that have “been diagnosed by a physician” (mean age=64.9 years, 65% male). AF patients were asked about their current treatments for AF or stroke prevention. Stroke prophylaxis patterns were identified as VKA only (VKA), ASA only (ASA), both VKA and ASA (VKA+ASA), and no VKA or ASA (non-VKA/ASA). Logistic regressions were used to examine factors associated with prophylaxis patterns, including demographics, health insurance, smoking, exercise, alcohol use, body mass index (BMI), modified Charlson comorbidity index , and CHADS 2 score (0, 1, or 2+). Results: Among AF participants, 343 (26.6%) were treated with VKA, 445 (34.5%) with ASA, 199 (15.4%) with VKA+ASA, and 303 (23.5%) with neither. Compared with non-VKA/ASA users, VKA or ASA users were more likely to be male, older, obese, and have a higher CHADS 2 score. Compared with VKA users, ASA users were younger and had more comorbidities. Multivariate logistic regression models showed that, compared with non-VKA/ASA use, obesity (OR=2.03, p=0.02), being married (OR=3.24, p=0.02), and male gender (OR=2.00, p=0.002) were associated with VKA+ASA use, and CHADS 2 ≥1 was associated with VKA or ASA use (OR≥1.69, p≤0.017). Comorbidities were associated with ASA versus VKA use (OR=1.68-3.79, p≤0.01). CHADS 2 score was not associated with VKA versus ASA use (p&gt;0.4). Conclusions: More than half of AF patients were not treated at all (23%) or treated with ASA only (34.5%) for stroke prevention. While older age, male gender, obesity, and stroke risk were associated with VKA or ASA treatment, CHADS 2 score was not related to VKA versus ASA treatment. Further study is needed to examine the clinical and economic consequences of VKA and ASA treatment among AF patients in a real-world setting.

Stroke and mortality in patients with incident heart failure: the Diet, Cancer and Health (DCH) cohort study

ObjectiveThe objective was to test the hypothesis that the risk of stroke, death and the composite of ‘stroke and death’ would be increased among patients with incident heart failure (HF)....

Monitoring new oral anticoagulants, managing thrombosis, or both?

Monitoring new oral anticoagulants, managing thrombosis, or both?

Perceived stress predicts the stability of vitamin K-antagonist treatment of anticoagulant clinic patients

Perceived stress predicts the stability of vitamin K-antagonist treatment of anticoagulant clinic patients -

Cécité secondaire à un surdosage en antivitamine K chez l’enfant : un argument pour l’éducation thérapeutique

Vitamin K antagonist (VKA) treatment is associated with significant risks and requires strict monitoring by measuring the international normalized ratio (INR), either by conventional methods or by self-measurement under medical supervision. We present a case of blindness occurring secondary to a moderate head injury, in a pediatric setting with no VKA therapeutic education. A 7-year-old child with a single ventricle had been operated on for a total cavopulmonary shunt at the age of 5 years. He took VKA therapy with an INR target between 2 and 3. After a head trauma, he had a frontal hematoma. His parents did not request a medical exam and did not check his INR. Six days after the injury, the INR was 2.23. The parents went to the emergency ward because the child had bilateral orbital hematoma. At admission, the INR was 5.6. The orbital hematoma was surgically evacuated in the emergency setting. Unilateral blindness occurred and remains a sequelae of the overdose. VKA treatment requires close supervision to prevent overdose, whose complications such as internal bleeding can have terrible consequences such as the case of blindness reported herein. This case report is a strong argument in favor of an educational program for children with VKA treatment.

Risk of bleeding in low-risk atrial fibrillation patients on warfarin waiting for elective cardioversion

IntroductionSystemic embolism is the most serious complication of cardioversion of atrial fibrillation (AF) and the immediate post-cardioversion period is associated with increased risk for thrombus formation. For this reason, treatment with vitamin K antagonist (VKA) is recommended for patients with AF. No information is available about bleeding risk related to this practice. MethodsWe performed a prospective multicentre study on 242 low-risk AF patients (CHADS2 score 0–1) that started on warfarin for elective cardioversion to evaluate their bleeding risk. Results178 were males (73.6%), mean age 63.9±9.8years, 60 patients (25%) were aged ≤59years. Patients with CHADS2 score=0 were 73 (30%), those with CHADS2 score=1 were 169 (70%). Patients were on VKA treatment, maintained at INR intended therapeutic range 2.0-3.0, for a median time of 159days (range 30–631)total follow-up period 127 patient-years (pt-yrs). Quality of anticoagulation and occurrence of bleeding events were recorded. Patients spent 23%, 64% and 8% of time below, within and above the intended therapeutic range, respectively. When we observed the INR levels, we found that 62 patients (25.6%) had INR>4.5 at least in one occasion, and 23 (9.5%) in ≥2. During follow-up, 2 patients had major bleeds (rate 1.6% pt-yrs), one fatal. No embolic complications were recorded. ConclusionOur results show that low-risk AF patients, treated with VKA for elective cardioversion, carry a not irrelevant risk of bleeding. Efforts are required to properly select patients who could benefit from this procedure, reducing the time of warfarin exposure.

Effect on perfusion chamber thrombus size in patients with atrial fibrillation during anticoagulant treatment with oral direct thrombin inhibitors, AZD0837 or ximelagatran, or with vitamin K antagonists

IntroductionAZD0837 and ximelagatran are oral direct thrombin inhibitors that are rapidly absorbed and bioconverted to their active forms, AR-H067637 and melagatran, respectively. This study investigated the antithrombotic effect of AZD0837, compared to ximelagatran and the vitamin K antagonist (VKA) phenprocoumon (Marcoumar®), in a disease model of thrombosis in patients with non-valvular atrial fibrillation (NVAF). MethodsOpen, parallel-group studies were performed in NVAF patients treated with VKA, which was stopped aiming for an international normalized ratio (INR) of ≤2 before randomization. Study I: 38 patients randomized to AZD0837 (150,250 or 350mg) or ximelagatran 36mg twice daily for 10–14days. Study II: 27 patients randomized to AZD0837 250mg twice daily or VKA titrated to an INR of 2–3 for 10–14days. A control group of 20 healthy elderly subjects without NVAF or anticoagulant treatment was also studied. Size of thrombus formed on pig aorta strips was measured after a 5-minute perfusion at low shear rate with blood from the patient/control subject. ResultsThrombus formation was inhibited by AZD0837 and ximelagatran. Relative to untreated patients, a 50% reduction of thrombus size was estimated at plasma concentrations of 0.6 and 0.2μmol/L for AR-H067637 and melagatran, respectively. For patients receiving VKA treatment, the thrombus size was about 15% lower compared with healthy elderly controls. ConclusionsEffects of AZD0837 and ximelagatran on thrombus formation were similar or greater than for VKA therapy and correlated with plasma concentrations of their active forms.

Ulcères de jambe nécrotiques induits par les anti-vitamines K : à propos de cinq cas

Vitamin K antagonists (VKAs) are widely used in thromboembolic diseases. We report five cases of necrotic leg ulcers having a particularly severe course and in which withdrawal of VKA treatment alone enabled healing. Five patients presented with necrotic leg ulcers clinically evocative of necrotic angiodermatitis or vasculitis. Histological features were variable, including inconstantly inflammatory lesions (leukocytoclastic vasculitis) and microthrombosis. None of the patients had laboratory signs of autoimmune disease. Healing occurred in all patients only after withdrawal of VKA therapy (fluindione or acenocoumarol). Associated vascular diseases included superficial venous, distal arterial insufficiency and postphlebitic disease. In three cases, thrombotic factors were observed: hyperhomocysteinaemia or heterozygous Factor V Leiden mutation. Although the causative role of VKAs is based solely on chronological criteria, this potential side effect deserves publication because of its practical therapeutic consequences. The physiopathological mechanisms accounting for the role of VKAs, including immunoallergic phenomena and, above all, microcirculatory thrombotic processes, are hypothetical and not universally accepted.

Patients using vitamin K antagonists show increased levels of coronary calcification: an observational study in low-risk atrial fibrillation patients

Vitamin K antagonists (VKA) are currently the most frequently used drug to prevent ischaemic stroke in atrial fibrillation (AF) patients. However, VKA use has been associated with increased vascular calcification. The aim of this study was to investigate the contribution of VKA use to coronary artery calcification in low-risk AF patients. A prospective coronary calcium scan was performed in 157 AF patients without significant cardiovascular disease (108 males; mean age 57 ± 9 years). A total of 71 (45%) patients were chronic VKA users. The duration of VKA treatment varied between 6 and 143 months (mean 46 months). No significant differences in clinical characteristics were found between patients on VKA treatment and non-anticoagulated patients. However, median coronary artery calcium scores differed significantly between patients without and patients with VKA treatment [0, inter-quartile range (IQR) 0-40, vs. 29, IQR 0-184; P = 0.001]. Mean coronary calcium scores increased with the duration of VKA use (no VKA: 53 ± 115, 6-60 months on VKA: 90 ± 167, and >60 months on VKA: 236 ± 278; P < 0.001). Multivariable logistic regression analysis revealed that age and VKA treatment were significantly related to increased coronary calcium score. Patients using VKA show increased levels of coronary calcification. Age and VKA treatment were independently related to increased coronary calcium score.