Lege Artis Medicinae

[New treatment option for oral anticoagulation in the prevention of cardiogenic stroke - Focus on the RE-LY trial]


MARCH 20, 2011

Lege Artis Medicinae - 2011;21(03)

[Atrial fibrillation (AF) represents the most common cause of cardioembolic stroke. The prevalence of AF increases with age and affects 10% of elderly people. AF-related stroke is usually severe and has a high mortality. The risk of stroke can be estimated on the basis of risk factors accompanying AF and age. Patients with one of the highest risk are those with AF and previous TIA or stroke. Efficient prevention is achieved by chronic anticoagulation therapy. In clinical practice, the use of vitamin K antagonists (VKA) has been the only option. The use of these agents is limited for a number of reasons, and clinicians are especially reluctant to use them in elderly patients at high risk of stroke. Consequently, of the patients with AF for whom anticoagulant therapy is indicated, only about 50-60% receives such therapy, and only half of the treated patients achieves target INR values. More than 50 years after the introduction of warfarin, data of trials with the new direct thrombin inhibitor dabigatran have been published in the past few years. In this paper, we review the results of the phase III, international RE-LY trial, published in 2009, which evaluated the preventive efficacy dabigatran etexilate in patients with AF compared with warfarin at a therapeutic dose. On the basis of the results, dabigatran used at a dose of 2×110mg daily provides the same protection as warfarin, whereas at a dose of 2×150mg it provides a signiificantly more efficient protection from AF-associated stroke and systemic embolism. In addition to its excellent preventive effect, dabigatran tretament results in a significant decrease in the risk of intracranial haemorrhages, and of other major haemorrhages. On the basis of the results, dabigatran will probably change the current treatment paradigm in the stroke prevention in patients with AF, and its introduction can substantially increase the number of patients treated efficiently and safely.]



Further articles in this publication

Lege Artis Medicinae

[Analysis of short-term and long-term survival and causes of death in patients with systemic lupus erythematosus]

TARR Tünde, KISS Emese, SZEGEDI Gyula, ZEHER Margit

[INTRODUCTION - In systemic lupus erythematosus (SLE), both short-term and long-term survival rates have improved worldwide. We analysed retrospectively the short-term and long-term survival data and causes of death at a single center. These data were compared with previous survival data recorded at the same centre and published in international studies. PATIENTS AND METHOD - The data of 550 patients with SLE were analysed between 1970 and 2009. We examined the effect of clinical symptoms, age, severity and onset of the disease and the applied immunosuppressive treatment on survival, using the Kaplan-Meier method. RESULTS - Survival rates at 5, 10, 15 and 20 years after the diagnosis were 98%, 94%, 90% and 89%, respectively. Late onset, neuropsychiatric symptoms and severe SLE were found to be prognostic factors. Manifestations affecting other organs and the applied immunosuppressive therapy did not influence survival rates. During the study period, 57 out of the 550 patients (10.4%) died. The main causes of death were cardiovascular complications (50.9%), infections (21%), and malignancies (12.3%). CONCLUSIONS - Our results show that among patients with SLE, it is mostly longterm survival that has increased, owing to the close control of patients. The increase in cardiovascular mortality highlights the importance of regular screening.]

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Lege Artis Medicinae

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Lege Artis Medicinae

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Lege Artis Medicinae

[JAK2 V617F: a new risk factor of stent thrombosis?]

PINCZÉS István, FEKETE Viktória, ZÁMOLYI Károly

[INTRODUCTION - Although the introduction of stents has dramatically improved the efficiency of percutaneous coronary interventions, a new complication, the stent thrombosis has appeared. Owing to intensive research, the incidence of this previously common complication is currently 1%. Because of the high mortality and morbidity, it is important to find more and more predictors, which might help to further reduce the incidence. CASE REPORT - Our elderly male patient presented with acute anterior myocardial infarct. Stent implantation of the left anterior descendent branch was performed using coronarography, with no complications. After five days without any symptoms, ST elevation recurred and subacute stent thrombosis was deteceted. Because of the laboratory results showing thrombocytosis, we performed JAK2 V617F screening, with a positive result. Prolonged heparin therapy, platelet aggegation inhibition at a transiently elevated dose and hydroxyurea treatment because of the myeloproliferativ malignancy were used. At the follow-up visit, the patient did not report any complaints, and cell counts for all three myeloid cell lines were in the normal range. CONCLUSION - The thrombogenic feature of the classic myeloproliferative disorders is well-known, and JAK2 V617F mutations further increase the risk. In our departement, screeing for such genetic alteration was performed in patients with stent thrombosis and a platelet count higher than 450 G/l. Two of the three cases had positive results. Supported by the literature, we think that the hematologic disease lead to the thrombotic complication in our patients. In our opinion, the JAK2 V617F is a potential risk factor of stent thrombosis.]

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Related contents

Lege Artis Medicinae

[Actual questions of the longterm anticoagulant therapy]

SAS Géza

[In the last few years we have witnessed some changes in the area of the chronic oral anticoagulant therapy. The nomenclature of the anticoagulant drugs has been modified and concern has arisen about the possible vascular calcification in patients on long-term warfarin therapy. Because of the novelty of the “new” anticoagulants (dabigatran etc.) has been lost, instead of their previous acronym (NOAC) the DOAC (direct oral anticoagulants) term has been accepted for their marking. Experimental and clinical data suggested that vitamin K-antagonists (VKA) in addition to the coagulation factors disturb the production of other proteins, too. By inhibiting the matrix Gla protein (MGP), the chronic warfarin therapy promotes the calcification in media of the arteries as it was shown in women participating in routine mammography. However, the clinical importance of this observation is dubious, because the incidence of acute coronary events is not increased in cases of warfarin therapy in patients with atrial fibrillation. Notwith­standing, in addition to the bleeding complications we have to take into account of the possible harmful vascular calcification, too, at the indication of chronic coumarin therapy. Therefore, this therapy should be applied only in proper cases, such as non-valvular atrial fibrillation with a high risk of ischaemic stroke or unprovoked venous thromboembolic disease with a high risk of recurrence. The results of the Swedish anticoagulant register show that the efficacy and safety of the well-managed coumarin therapy may be superior to the treatments with DOACs. However, DOACs are indispensable in certain cases in which a previous “probe” coumarin treatment is unfounded.]

Clinical Neuroscience

[The importance of anticoagulant therapy in patients with artial fibrillation in stroke prevention – summary of international data and novel therapeutic modalities]


[The most common cardiogenic cause of ischaemic stroke is atrial fibrillation which increases the probability of stroke five-fold and doubles case fatality. Based on international data the incidence of atrial fibrillation is approx. 2% however this rapidly increases with age. The necessity of using oral anticoagulants in the prevention of non-valvular atrial fibrillation related stroke is decided based on estimated stroke risk. The CHADS2 and the more predictive CHA2DS2-VASc scales are used for this purpose while the bleeding risk of patients treated with anticoagulant may be estimated by the HAS-BLED scoring scale. For decades oral anticoagulation meant using vitamin-K antagonists. Based on international data we can see that rate of anticoagulation is unacceptably low, furthermore most of the anticoagulated patients aren’t within the therapeutic range of INR (INR: 2-3). A lot of disadvantages of vitamin-K antagonists are known (e.g. food-drug interaction, need for regular coagulation monitoring, increased risk of bleeding), therefore compounds with new therapeutic target have been developed. The novel oral anticoagulants (NOAC) can be divided in two major subgroups: direct thrombin inhibitors (dabigatran etexilate) and Xa-factor inhibitors (rivaroxaban, apixaban, edoxaban). These products are administered in fix doses, they less frequently interact with other medications or food, and regular coagulation monitoring is not needed when using these drugs. Moreover several studies have shown that they are at least as effective in the prevention of ischaemic stroke than the vitamin-K antagonists, with no more haemorrhagic complications.]

LAM Extra for General Practicioners


KANCZ Sándor

[In this article, we summarise the available information on dabigatran, focusing on clinical practice, in particular on the prevention of stroke and systemic embolism, the critical aspects of anticoagulant treatment with dabigatran, potential drug-drug interactions and adverse reactions in nonvalvular atrial fibrillation. The most important molecular characteristics of dabigatran are also described. We highlight the implications of safety issues that have emerged during everyday clinical practice.]

Clinical Neuroscience


OLÁH László, CSÉPÁNY Tünde, BERECZKY Zsuzsanna, KERÉNYI Adrienne, MISZ Mária, KAPPELMAYER János, CSIBA László

[Introduction - Decreased activity of natural anticoagulants (antithrombin-III, protein C, protein S) rarely causes cerebral ischaemia, however it can be found frequently in acute phase of ischaemic stroke. The authors’ aim was to investigate whether the decreased activity of natural anticoagulants is accompanied by worsening of symptoms in ischaemic stroke. Patients and method - Sixty-eight acute ischaemic stroke patients were investigated. Severity of symptoms were assessed and followed by the NIH Stroke Scale. Antithrombin- III, protein C, protein S activities, and concentration of C-reactive protein (CRP) were measured within 48 hours after onset of ischaemic stroke. Results - Progressing stroke was found in 29% of patients. Decreased activity of at least one natural anticoagulant proteins was present in 31% of patients. Progression of stroke symptoms occured in 76% of patients with decreased natural anticoagulant activity, while this proportion was only 9% in those with normal natural coagulation inhibitor protein activity (p<0.01). Progressing stroke was also more frequent in patients with elevated CRP value (60%) than in those with normal CRP level (11%; p<0.05). Decreased activity of natural anticoagulants was more frequent in patients with elevated CRP concentration compared with patients with normal CRP. Conclusion - The results demonstrate the importance of decreased activity of natural anticoagulants in acute phase of ischaemic stroke. This abnormality was present in about 1/3 of stroke patients. The decreased activity of natural coagulant inhibitor proteins may play an important role in development of progressing stroke thus indicating unfavourable outcome.]

Journal of Nursing Theory and Practice

[Examination of cardio-vascular risk factors in the priority of atrial fibrillation]


[Objectives: Stroke-prophylaxis is the biggest question regarding atrial fibrillation. Their aim is to examine the risk factors, successfulness of frequency control, and the effectiveness of anticoagulant therapy. Methods: This quantitative cross-sectional study used a non-randomized sampling method. Enrollment criteria: anticoa-gulant therapy, atrial fibrillation, age 20-90 years, NYHA stage II. Excursion criteria: patients having elective intervention that influences INR rates. Patient data was collected from the records of the University of Pécs, Cardiology Clinic between 01.01.2012-31.12. They used linear regression, T-test, χ2-test, variance analysis (ANOVA), SPSS 20.0. Results: Significant correlation between BMI values-, systolic blood pressure-, modified medication and its effect on frequency control-, correct anticoagulant therapy, INR parameters and the increased risk of thromboembolia in patients with atrial fibrillation. (p<0.05) Conclusion: Stratification of risk factors and individual optimisation of anticoagulant therapy is important for effective stroke prevention and increased survival rate.]