Safety Of Anticoagulant Therapy Research Articles

The polyphosphate–factor XII pathway drives coagulation in prostate cancer-associated thrombosis

AbstractCancer is a leading cause of thrombosis. We identify a new procoagulant mechanism that contributes to thromboembolism in prostate cancer and allows for safe anticoagulation therapy development. Prostate cancer-mediated procoagulant activity was reduced in plasma in the absence of factor XII or its substrate of the intrinsic coagulation pathway factor XI. Prostate cancer cells and secreted prostasomes expose long chain polyphosphate on their surface that colocalized with active factor XII and initiated coagulation in a factor XII-dependent manner. Polyphosphate content correlated with the procoagulant activity of prostasomes. Inherited deficiency in factor XI or XII or high-molecular-weight kininogen, but not plasma kallikrein, protected mice from prostasome-induced lethal pulmonary embolism. Targeting polyphosphate or factor XII conferred resistance to prostate cancer-driven thrombosis in mice, without increasing bleeding. Inhibition of factor XII with recombinant 3F7 antibody reduced the increased prostasome-mediated procoagulant activity in patient plasma. The data illustrate a critical role for polyphosphate/factor XII-triggered coagulation in prostate cancer-associated thrombosis with implications for anticoagulation without therapy-associated bleeding in malignancies.

Feasibility and safety of uninterrupted dabigatran therapy in patients undergoing ablation for atrial fibrillation.

Uninterrupted oral warfarin strategy has become the standard protocol to prevent complications during catheter ablation (CA) for the treatment of atrial fibrillation (AF). However, little is known about the safety and efficacy of uninterrupted dabigatran therapy in patients undergoing CA for AF. Therefore, this study investigated the safety and efficacy of uninterrupted dabigatran therapy and compared the findings with those for uninterrupted warfarin therapy. Bleeding and thromboembolic events during the periprocedural period were evaluated in 363 consecutive patients who underwent CA for AF at Nagoya University Hospital, and received uninterrupted dabigatran (n=173) or uninterrupted warfarin (n=190) for periprocedural anticoagulation. A total of 27 (7%) patients experienced either bleeding or thromboembolic complications. Major bleeding complications occurred in 2 (1%) patients in the dabigatran group (DG) and 2 (1%) patients in the warfarin group (WG). Eight (5%) patients in the DG and 9 (5%) patients in the WG experienced groin hematoma, a type of minor bleeding complication. Meanwhile, no patient in the DG and 1 (1%) in the WG developed cerebral ischemic stroke. Overall, there was no significant difference between the groups for any category. The activated partial thromboplastin time (APTT) independently predicted periprocedural complications in the DG. Uninterrupted dabigatran therapy in CA for AF thus may be a safe and effective anticoagulant therapy, and appears to be closely similar to continuous warfarin; however, it is essential to pay close attention to the APTT values when using dabigatran during CA.

Strategy of sinus rhythm restoration after single stage correction of mitral valve defect and maze procedure for improvement of efficacy and safety of anticoagulant therapy

We analyzed clinical efficacy of a strategy of sinus rhythm (SR) restoration after single stage correction of mitral valve defect and failed radiofrequency maze procedure elaborated and realized in the Research Institute for Complex Issues of Cardiovascular Diseases, and assessed its value for increase of efficacy and safety of anticoagulant therapy. First stage of this strategy--cardiosurgical treatment with maze procedure--resulted in restoration of SR in 61.8% of cases. In case of persistence of tachyarrhythmia external elelectro-impulse therapy was used in 1-1.5 months after cardiac surgery as a second stage of our strategy. Third stage--catheter radiofrequency ablation--was applied to patients with implanted biological cardiac valves. Second and third stages facilitated restoration of SR in 84.8 and 93.2% of patients, respectively, and provided 100% SR restoration in patients with biological valve prostheses. The suggested strategy allowed to withdraw anticoagulant therapy in patients with biological valves and to reduce level of hypocoagulation to lower limit of target range in patients with mechanical prostheses.

Anticoagulant treatment for subsegmental pulmonary embolism.

Acute pulmonary embolism (PE) is a common cause of death, accounting for 50,000 to 200,000 deaths annually. It is the third most common cause of mortality among the cardiovascular diseases, after coronary artery disease and stroke.The advent of multi-detector computed tomographic pulmonary angiography (CTPA) has allowed better assessment of PE regarding visualisation of the peripheral pulmonary arteries, increasing its rate of diagnosis. More cases of peripheral PEs, such as isolated subsegmental PE (SSPE) and incidental PE, have thereby been identified. These two conditions are usually found in patients with few or none of the classic PE symptoms such as haemoptysis or pleuritic pain, acute dyspnoea or circulatory collapse. However, in patients with reduced cardio-pulmonary (C/P) reserve the classic PE symptoms can be found with isolated SSPEs. Incidental SSPE is found casually in asymptomatic patients, usually by diagnostic imaging performed for other reasons (for example routine CT for cancer staging in oncologic patients).Traditionally, all PEs are anticoagulated in a similar manner independent of the location, number and size of the thrombi. It has been suggested that many patients with SSPE may be treated without benefit, increasing adverse events by possible unnecessary use of anticoagulants.Patients with isolated SSPE or incidental PE may have a more benign clinical presentation compared with those with proximal PEs. However, the clinical significance in patients and their prognosis have to be studied to evaluate whether anticoagulation therapy is required. To assess the effectiveness and safety of anticoagulation therapy versus no intervention in patients with isolated subsegmental pulmonary embolism (SSPE) or incidental SSPE. The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). MEDLINE, EMBASE, LILACS and clinical trials databases were also searched (October 2013). Randomised controlled trials of anticoagulation therapy versus no intervention in patients with SSPE or incidental SSPE. Two review authors inspected all citations to ensure reliable selection. We planned for two review authors to independently extract data and to assess the methodological quality of identified trials using the criteria recommended in the Cochrane Handbook for Systematic Reviews of Interventions. No studies were identified that met the inclusion criteria. There is no randomised controlled trial evidence for the effectiveness and safety of anticoagulation therapy versus no intervention in patients with isolated subsegmental pulmonary embolism (SSPE) or incidental SSPE, and therefore we can not draw any conclusions. Well-conducted research is required before informed practice decisions can be made.

Safety of Chronic Anticoagulation Therapy After Endovascular Abdominal Aneurysm Repair (EVAR)

Current data supporting the effect of anticoagulation drug use on aneurysm sealing and the durability of endovascular abdominal aneurysm repair (EVAR) are conflicting. This study assessed the safety of chronic anticoagulation therapy after EVAR. Records of 1409 consecutive patients having elective EVAR during 1997-2011 who were prospectively followed were reviewed. Survival, reintervention, conversion, and endoleak rates were analyzed in patients with and without chronic anticoagulants. Cox proportional hazards models were used to estimate the effect of anticoagulation therapy on outcomes. One-hundred and three (7.3%) patients were on chronic anticoagulation drugs (80 on vitamin K antagonists) at the time of EVAR. An additional 46 patients started on anticoagulants after repair were identified. Patients on chronic anticoagulation therapy at repair (mean age 73.6 years; 91 males) had more frequent cardiac disease (74.8% vs. 44.2%; p < 00001), but no other differences in demographic and major baseline comorbidities with respect to the others. At baseline, mean abdominal aortic aneurysm (AAA) diameter was 56.43 mm vs. 54.65 mm (p = .076) and aortic neck length 26.54 mm vs. 25.21 mm (p = .26) in patients with and without anticoagulants, respectively. At 5 years, freedom from endoleak rates were 55.5% vs. 69.9% (p < .0001), and freedom from reintervention/conversion rates were 69.4% vs. 82.4% (p < .0001) in patients with (including those with delayed drug use) and without chronic anticoagulants, respectively. Controlling for covariates with the Cox regression method, at a mean follow-up of 64.3 ± 45.2 months after EVAR, use of anticoagulation drugs was independently associated with an increased risk of endoleak (odds ratio, OR 1.6; 95% confidence interval, CI: 1.23-2.07; p < .0001) and reintervention or late conversion rates (OR 1.8; 95% CI: 1.31-2.48; p < .0001). The safety of anticoagulation therapy after EVAR is debatable. Chronic anticoagulation drug use risks exposure to a poor long-term outcome. A critical and balanced decision-making approach should be applied to patients with AAA and cardiac disease who may require prolonged anticoagulation treatment.

Drug adherence in patients taking oral anticoagulation therapy

Oral anticoagulation has proven to reduce mortality and morbidity of thromboembolic events. One of the most important determinants of the effectiveness and safety of anticoagulation therapy is the adherence to the prescribed therapy. Vitamin K antagonists are characterized by under-utilization, a narrow therapeutic window and multiple food and drug interactions which contribute to a variable dose-response relationship with the risk of insufficient protection and/or increased bleeding risk. The "new" direct oral anticoagulants have demonstrated equal or superior protection and reduced bleeding risks compared to warfarin and are easier to use because of fixed dosing without monitoring of anticoagulation. Controlling of adherence to the direct oral anticoagulants is difficult. Therefore, continuous and regular medication intake represents a pre-requisite for achieving optimal protection. The present review aims to give an overview about the factors that affect drug adherence in patients taking oral anticoagulation drugs and discusses strategies to improve drug adherence.

Usefulness of Dabigatran Etexilate as Periprocedural Anticoagulation Therapy for Atrial Fibrillation Ablation

The usefulness of dabigatran etexilate for the prevention of stroke in patients with atrial fibrillation (AF) has been reported. In this study the efficacy and safety of dabigatran etexilate for anticoagulation for AF ablation were examined. Patients were divided into three groups: Group 1, interrupted warfarin bridged by heparin between pre- and post-ablation; Group 2, continuous warfarin therapy; and Group 3, dabigatran etexilate therapy. Anticoagulation therapy with warfarin or dabigatran etexilate was performed from 30 days before to at least 90 days after AF ablation. Dabigatran etexilate was administered at 110 or 150 mg twice daily, depending on renal function and age. Patients' clinical characteristics, associated disorders, echocardiographic parameters and arrhythmia status were not different among the three groups. Procedural parameters such as procedural time and radiofrequency energy supply were also not different among the three groups. The dabigatran etexilate group and the warfarin groups had no embolic complications (stroke, cerebral transient ischaemic attack, deep venous thrombosis or pulmonary embolism). No pericardial tamponade was observed in the dabigatran etexilate group, while two patients in each of Group 1 (2/194, 1.0 %) and Group 2 (2/203, 0.98 %) developed cardiac tamponade, though the differences were not significant. Pericardial effusion and groin haematoma were observed in one patient each (1/105, 0.9 %) in the dabigatran etexilate group, and the incidences were not different from the warfarin group (Group 1: 4/194, 2.1 % and 2/194, 1.0 %; Group 2: 3/203, 1.5 % and 2/203, 1.0 %, respectively). As a whole, the safety outcomes did not differ among the three groups. Dabigatran etexilate is an effective and safe anticoagulation therapy for AF ablation. Thus, dabigatran etexilate appears to be useful as an alternative anticoagulant therapy to warfarin for AF ablation.

The arrival of genomic medicine to the clinic is only the beginning of the journey

The arrival of genomic medicine to the clinic is only the beginning of the journey

APPLICATIONS OF PHARMACOGENETIC TESTING FOR PERSONALIZATION OF THERAPY WITH ORAL ANTICOAGULANTS IN RUSSIA

The clinical significance of the patient genetic characteristics in the individual pharmacological response to oral anticoagulants is considered. Possible tactics of warfarin dosing and new oral anticoagulants choice on the basis of pharmacogenetic testing as well as indications for this approach in clinical practice are discussed. It should increase efficacy and safety of anticoagulant therapy.

Anticoagulation for cerebral venous sinus thrombosis.

Treatment of cerebral venous thrombosis with anticoagulants may prevent new venous infarcts, neurological deterioration, and pulmonary embolism but may also promote hemorrhages. ### Objectives The objective of the study was to assess the efficacy and safety of anticoagulant therapy in patients with radiologically confirmed cerebral venous thrombosis. This is an update of the 2002 version of the Cochrane Review on this topic.1 ### Search Strategy We searched the Cochrane Stroke Group Trials Register (last searched August 2010), MEDLINE (1950 to August 2010), EMBASE (1980 to August 2010), and the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011 Issue 1). In an effort to identify further published, unpublished, and ongoing trials, we searched ongoing trial registers and reference lists of relevant articles and contacted the authors. ### Selection Criteria Selection criteria included nonconfounded randomized controlled trials in which anticoagulant …

Safety of anticoagulants in children with arterial ischemic stroke

AbstractPediatric arterial ischemic stroke (AIS) is increasingly diagnosed and carries significant risks of recurrence, morbidity, and mortality. Anticoagulant therapy (ACT) is commonly prescribed in childhood AIS. Hemorrhagic complication rates in pediatric stroke are unknown, and adult safety data are of limited applicability. We analyzed a prospectively enrolled cohort of children (aged 1 month-18 years) with acute AIS selected using standardized criteria for protocol-based ACT over14-year period. We assessed ACT-associated intracranial hemorrhage (ICH), including frequency, clinical and radiologic characteristics, predictors, and outcome. Among 215 children with AIS, 123 received ACT within 7 days after diagnosis. During anticoagulation, 14 (11%) children developed new or increased ICH, all within 26 days from diagnosis. ICH was symptomatic in 5 (4%), asymptomatic in 9 (7%), and mild (European Cooperative Acute Stroke Study grades HI1 or HI2) in all but 1 child (ECASS PH-2). Long-term neurologic outcomes after ACT-associated ICH in survivors were abnormal in 73% (8/11). Comparably, 12 of 75 (16%) children treated without anticoagulation developed new or increased ICH on follow-up imaging (P = .3507). We conclude that ACT is relatively safe in children with AIS, with a 4% risk of symptomatic ICH. Based on the safety of ACT in our study, clinical trials of ACT in childhood AIS are warranted.

Prospective evaluation of a pharmacogenetics-guided warfarin loading and maintenance dose regimen for initiation of therapy

AbstractSingle-nucleotide polymorphisms in genes that affect warfarin metabolism (cytochrome P450 2C9 gene, CYP2C9) and response (vitamin K epoxide reductase complex 1 gene, VKORC1) have an important influence on warfarin therapy, particularly during initiation; however, there is a lack of consensus regarding the optimal pharmacogenetics-based initiation strategy. We conducted a prospective cohort study in which patients requiring warfarin therapy for atrial fibrillation or venous thromboembolism were initiated with a novel pharmacogenetics-initiation protocol (WRAPID, Warfarin Regimen using A Pharmacogenetics-guided Initiation Dosing) that incorporated loading and maintenance doses based on genetics, clinical variables, and response (n = 167, followed up for 90 days), to assess the influence of genetic variations on anticoagulation responses. Application of the WRAPID algorithm resulted in a negligible influence of genetic variation in VKORC1 or CYP2C9 on time to achievement of first therapeutic response (P = .52, P = .28) and risk of overanticoagulation (P = .64, P = .96). After adjustment for covariates, time to stable anticoagulation was not influenced by VKORC1 or CYP2C9 genotype. Importantly, time spent within or above the therapeutic range did not differ among VKORC1 and CYP2C9 genotype groups. Moreover, the overall time course of the anticoagulation response among the genotype groups was similar and predictable. We demonstrate the clinical utility of genetics-guided warfarin initiation with the WRAPID protocol to provide safe and optimal anticoagulation therapy for patients with atrial fibrillation or venous thromboembolism.

New allele-specific real-time PCR system for warfarin dose genotyping equipped with an automatic interpretative function that allows rapid, accurate, and user-friendly reporting in clinical laboratories

IntroductionThe optimal dose of the oral anticoagulant warfarin varies with polymorphisms of the vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9) genes. A fast and reliable method of warfarin dose adjustment is required to prevent serious hemorrhagic or thrombotic complications. The aim of this study is to develop and validate a new warfarin dose genotyping system with an automatic interpretation function. Materials and methodsFour VKORC1 and two CYP2C9 SNPs were genotyped by real-time PCR using allele-specific primers and probes. Multiple reactions that included internal positive controls were performed in each well, and an automatic interpretative algorithm was developed. This system was validated using 82 clinical specimens previously genotyped by PCR-direct sequencing. The analytical time of the method was calculated. ResultsNo interference was observed when multiple samples were included in each reaction, with all internal positive control reactions being successful. In the genotyping algorithm, Ct differences <2 and ≥2 identified heterozygotes and homozygotes, respectively. All results obtained were concordant with those of the reference method. The overall analytical time for assay of 12 specimens was around 3 hours. ConclusionThis rapid, accurate, and user-friendly genotyping system improves the efficacy and safety of anticoagulation therapy in clinical practice.

Anticoagulation for cerebral venous sinus thrombosis

Treatment of cerebral venous sinus thrombosis with anticoagulants has been controversial. Anticoagulants may prevent new venous infarcts, neurologic deterioration and pulmonary embolism but may also promote haemorrhages. To assess the effectiveness and safety of anticoagulant therapy in patients with confirmed cerebral venous sinus thrombosis. We searched the Cochrane Stroke Group Trials Register (last searched August 2010), MEDLINE (1950 to August 2010), EMBASE (1980 to August 2010) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, 2011 Issue 1). In an effort to identify further published, unpublished and ongoing trials we searched ongoing trials registers and reference lists of relevant articles, and contacted authors. Unconfounded randomised controlled trials in which anticoagulant therapy was compared with placebo or open control in patients with cerebral venous sinus thrombosis (confirmed by intra-arterial contrast, or venography with magnetic resonance, or venography with computed tomography imaging). Two review authors independently extracted outcomes for each of the two treatment groups (anticoagulant treatment and control). The outcome data for each patient were analysed in the treatment group to which the patient was originally allocated (intention-to-treat analysis). We calculated a weighted estimate of the treatment effects across trials (relative risk, absolute risk reduction). We included two small trials involving 79 patients. One trial (20 patients) examined the efficacy of intravenous, adjusted dose unfractionated heparin. The other trial (59 patients) examined high dose, body weight adjusted, subcutaneous, low-molecular weight heparin (nadroparin). Anticoagulant therapy was associated with a pooled relative risk of death of 0.33 (95% confidence interval (CI) 0.08 to 1.21) and of death or dependency of 0.46 (95% CI 0.16 to 1.31). The absolute reduction in the risk of death or dependency was 13% (95% CI 30% to -3%). No new symptomatic intracerebral haemorrhages were observed. One major gastro-intestinal haemorrhage occurred after anticoagulant treatment. Two control patients (placebo) had a diagnosis of probable pulmonary embolism (one fatal). Based upon the limited evidence available, anticoagulant treatment for cerebral venous sinus thrombosis appeared to be safe and was associated with a potentially important reduction in the risk of death or dependency which did not reach statistical significance.

Venous Thromboembolic Events With Chemotherapy Plus Bevacizumab: A Pooled Analysis of Patients in Randomized Phase II and III Studies

Thromboembolism is a major source of morbidity and mortality in patients with cancer. The contribution of anti-vascular endothelial growth factor therapy to these events remains controversial. Individual patient data were available for 6,055 patients in 10 randomized studies. Unadjusted and exposure-adjusted incidence of venous thromboembolisms (VTEs) was estimated for the overall population and by tumor type. Multivariate analysis was performed to identify risk factors for development of VTE. The safety of anticoagulant therapy in patients undergoing bevacizumab treatment was also examined. There were no statistically significant increases in the unadjusted or exposure-adjusted incidences of all-grade VTEs for bevacizumab versus controls in the overall population or by tumor type. The unadjusted incidence in the overall population was 10.9% with bevacizumab versus 9.8% with controls (odds ratio, 1.14; 95% CI, 0.96 to 1.35; P = .13); the rate per 100 patient-years was 18.5 for bevacizumab and 20.3 for controls (rate ratio, 0.91; 95% CI, 0.77 to 1.06; P =.23). Incidences of grade 3 to 5 events were similar in both groups. Several risk factors for VTEs were identified, including tumor type, older age, poorer performance status, VTE history, and baseline oral anticoagulant use. No interactions between bevacizumab treatment and these factors were observed. For patients who had a VTE and received full-dose anticoagulation therapy, the risk of severe bleeding was low (< 1%) and unaffected by bevacizumab treatment. The addition of bevacizumab to chemotherapy did not statistically significantly increase the risk of VTEs versus chemotherapy alone. The risk for VTEs is driven predominantly by tumor and host factors.

Venous thromboembolism in nonagenarians

The balance between the efficacy and safety of anticoagulant therapy in patients aged >/=90 years with venous thromboembolism (VTE) is uncertain. RIETE is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic VTE. We evaluated the efficacy and safety of anticoagulant therapy during the first three months in all patients aged >/=90 years. In addition, we tried to identify those at a higher risk for VTE. Of 21,873 patients enrolled from March 2001 to February 2008, 610 (2.8%) were aged >/=90 years. Of these, 307 (50%) presented with pulmonary embolism (PE), 240 (39%) had immobility >/=4 days, and 271 (44%) had abnormal creatinine levels. During the first three months of therapy, 140 patients aged >/=90 years (23%) died. Of these, 45 (32%) died of PE (34 of the initial episode, 11 of recurrent PE), 18 (13%) had fatal bleeding. Recent immobility >/=4 days was the most common risk factor for VTE (240 of 610 patients, 39%), but only 54 of them (22%) had received thromboprophylaxis. The most frequent causes for immobility were senile dementia, acute infection, trauma or decompensated heart failure. The duration of immobility was <4 weeks in 126 patients (52%), and most of them were bedridden at home. In conclusion, one in every four VTE patients aged >/=90 years died during the first three months of therapy. Of these, one in every three died of PE, one in every eight had fatal bleeding. Identifying at-risk patients may help to prevent some of these deaths.

SAFETY OF LONGTERM THERAPY WITH WARFARIN: POSSIBILITY OF TREATMENT RENEWING AFTER HEMORRHAGIC COMPLICATIONS

The safety of anticoagulant therapy is discussed. Warfarin position in prevention of thrombotic complications is analyzed according to the evidence base medicine approach. Possible hemorrhagic complications of warfarin are described and accompanied with clinical cases. Possibility of renewal of anticoagulant therapy in patients after hemorrhagic complications is discussed.

Management of venous thromboembolism (VTE) in melanoma patients with brain metastasis

9522 Background: Venous thromboembolism (VTE) is a frequent complication in melanoma pts with brain metastases (BM). Because these pts are at very high risk of intracranial bleeding, treating VTE in this population is challenging. Limited data is available regarding the safety of anti-coagulation therapy (TX). Herein we evaluate the clinical outcome of our pts. Methods: Data was collected retrospectively on pts with BM that had deep venous thrombosis (DVT) and/or pulmonary embolism (PE). Eight-one pts were included in the analysis. The purpose of the study was to assess whether TX with anticoagulation would affect the development of hemorrhage post-VTE. Two endpoints are of interest: 1) Overall survival and 2) Development of hemorrhage post-VTE. Cox proportional hazards regression methodology was used for analyses of survival. Analyses of hemorrhage were performed using logistic regression or Fisher’s exact tests. The covariates of interest included VTE therapy (IVC filter vs. anticoagulant vs. both vs. neither), VTE event (DVT vs. PE vs. both), VTE symptoms, DVT location and/or PE, pattern and location of BM (solitary, multiple, hemorrhagic), size of largest BM lesion, co-morbidities, and systemic chemotherapy. Results: 60/81 pts were given anticoagulation. 6/60 pts receiving anticoagulation developed hemorrhage within 1 month (4 intracranial, 1 GI tract, 1 bladder), which was not statistically different from 5 of 21 pts who developed hemorrhage within 1 month in the absence of anticoagulation (3 intracranial, 1 GI tract, 1 adrenal). Of the 6 pts who developed hemorrhage on anticoagulation, 2/6 pts remain alive after 5 and 6 months post VTE and 4 died due to PD. Regimens that included low molecular weight heparin (LMWH) vs. heparin or vitamin K antagonists alone or in combination, showed improved overall survival p=0.033. Hazard ratios (HR) for IVC filter, anticoagulant, and the combination ranged from 0.17 to 0.37. No statistically significant differences in survival were seen between pts treated with anticoagulation alone, IVC filter alone, or the combination of the two. Conclusions: Anticoagulants did not increase the risk of hemorrhage. The presence of BM without evidence of hemorrhage is not a contraindication for the use of anticoagulation therapy. No significant financial relationships to disclose.

Current Status of Anticoagulation Therapy for Elderly Atrial Fibrillation Patients in Japan From Hokuriku Atrial Fibrillation Trial

The number of the elderly patients with atrial fibrillation (AF) is increasing, but the current status of anticoagulation therapy for elderly patients with AF in Japan is not clear. Among the patients registered in the "Hokuriku Atrial Fibrillation Trial (HAT) 1", 365 AF patients aged > or =65 years were enrolled in this study. Warfarin was used for significantly less patients in the oldest group aged > or =85 years (36%) than in younger populations, but the percentage of antiplatelet use in this oldest population was largest (40%). The elderly group (> or =85 years) was compared with a younger group aged between 75 and 84 years. Warfarin was given to 61% of the younger group compared with 36% in the elderly group. In the younger group, the more thromboembolic risks they had according to CHADS2 score, the more warfarin was used, whereas there was no clear trend in the usage of warfarin in the elderly group. The number of elderly Japanese patients with AF taking warfarin is currently low, but because the population of elderly AF patients will increase in the future, there is a need for safe and suitable anticoagulation therapy for elderly patients.

Prognosis and Safety of Anticoagulation in Intracranial Artery Dissections in Adults

To characterize different forms of intracranial artery dissections (IADs), and to test the assumption that IADs are frequently associated with subarachnoid hemorrhage (SAH) and poor outcome, and that anticoagulant therapy is contraindicated in these patients. We studied 81 consecutive non-SAH IAD patients and 22 IAD patients with SAH, diagnosed between 1994 and 2004 and 1998 and 2004, respectively, and treated the former patients immediately with heparin, followed with at least 3 months of warfarin. Outcomes were recorded at 3 months. Approximately one-third of all cervicocephalic artery dissections were identifiably either completely located intracranially or extended into the intracranial space. At 3 months, 64 of the 81 non-SAH patients (79%) had a favorable outcome (modified Rankin Scale, 0 to 2); 1 patient died of brain infarction in the acute stage. Only 1 aneurysm developed during follow-up in the non-SAH group, and no intracranial bleeding was observed during anticoagulant treatment. Those presenting with SAH formed approximately 25% of all IADs, and 21 cases out of 22 (95%) were associated with ruptured fusiform dissecting aneurysm. This latter group displayed significantly worse outcomes: 7 died, and only 7 had modified Rankin Scale 0 to 2 at 3 months. Our results provide important information for clinical practice. IADs appear to polarize into 2 groups: (1) nonaneurysmatic IADs presenting without SAH that are associated with favorable outcomes and safe anticoagulant therapy; and (2) aneurysmatic IADs, characterized by SAH and poorer prognosis. Literature on IADs may have been biased toward group 2.