LAM Extra for General Practicioners

[DABIGATRAN: A NEW ORAL ANTICOAGULANT AGENT FOR THE PREVENTION OF STROKE AND SYSTEMIC EMBOLISM IN NONVALVULAR ATRIAL FIBRILLATION]

KANCZ Sándor

MARCH 20, 2013

LAM Extra for General Practicioners - 2013;5(01)

[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.]

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LAM Extra for General Practicioners

[NON-HDL-CHOLESTEROL AND ITS SIGNIFICANCE]

SIMONYI Gábor

[The role of LDL-cholesterol in cardiovascular risk has been established in a number of studies. According to current recommendations, therefore, the primary goal of lipidlowering therapy is reducing the level of LDL-cholesterol. Of lipid-lowering drugs, statins are the most efficient in reducing cardiovascular risk. According to large studies on statins, however, there is a significant residual risk even in patients receiving aggressive treatment. It is well known that many patients continue to have dyslipidaemia despite statin therapy, and not all patients with cardiovascular disease have elevated LDL-cholesterol levels. These observations indicate that lipids other than LDL-cholesterol also have a role in the development of atherosclerosis. A growing attention is paid to non-HDL-cholesterol as a cardiovascular risk factor. Calculating non-HDL-cholesterol target is easy: LDL-cholesterol measurement plus 0,8. Non-HDL-cholesterol incorporates a number of atherogenic lipoprotein particles [VLDL-cholesterol, IDL-cholesterol, LDL-cholesterol, and lipoprotein(a)]. As the atherogenic effect of apoB-containing lipoproteins (LDL, IDL-C és VLDL) is significant, they may be stronger predictors of coronary heart disease (CHD) risk than LDL-cholesterol is. Considering the strong correlation between apoB and non-HDLcholesterol and the limitations of apoB measurement (standardisation, cost), non- HDL-cholesterol is a more useful parameter and therapeutic target, especially if triglyceride levels are greater than 2.26 mmol/l.]

LAM Extra for General Practicioners

[THE BIOLOGICAL BASIS OF SCREENING: NATURAL HISTORY OF MALIGNOUS TUMOURS]

DÖBRŐSSY Lajos, KOVÁCS Attila, BUDAI András

[The development of malignous tumours is a prolonged, multistage process. The onset of clinical symptoms and subjective complaints is preceded by the preclinical detectable phase, during which the tumour does not cause any symptoms but it has some signs and can be detected by screening. Information on the tumour’s natural history is of practical importance for choosing the screening strategy. When evaluating screening results, the various biases related to biological reasons need to be taken into consideration.]

LAM Extra for General Practicioners

[ANTIDIABETIC THERAPY OF PATIENTS WITH TYPE 2 DIABETES MELLITUS - THE PLACE OF INSULIN ADMINISTRATION]

GYIMESI András

LAM Extra for General Practicioners

[EXPERIENCE WITH COENZYME Q10 IN HEART FAILURE]

KOHUT László

[INTRODUCTION - The protein complex coenzyme Q10 (CoQ10) has a role in ATP production as a mitochondrial electron transport molecule, and it also has a strong antioxidant effect. Several studies have proved the correlation between the decrease in CoQ10 level and the severity of heart failure. Heart failure is a multifactorial syndrome, the development of which is greatly influenced by an abnormal energy metabolism. CASE REPORT - The 61-year-old woman developed heart failure after a myocardial infarction. She complained of fatigue, dyspnoea and reduced physical endurance even with optimal treatment. When her therapy was completed by CoQ10, her endurance and life quality significantly improved and her symptoms ameliorated. CONCLUSIONS - Medical treatment of chronic heart failure is an evidence-based, complex therapy. Despite the complex management, morbidity and mortality of this condition remain high. A number of studies have shown that CoQ10 substitution can improve the clinical and haemodynamical parameters of patients with heart failure. On the basis of these results, the use of CoQ10 as an adjuvant therapy to complex treatment has an increasing role.]

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Lege Artis Medicinae

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

SZAPÁRY László

[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.]

Clinical Neuroscience

[Effective, safe stroke prevention with novel oral anticoagulants in patients with atrial fibrillation. Focus on dabigatran]

SZAPÁRY László, FEHÉR Gergely, BOSNYÁK Edit, DELI Gabriella, CSÉCSEI Péter

[Non-valvular AF is the most common cardiac arrhytmia. Its incidence increases with age. AF is an independent risk factor for ischaemic stroke, representing a five times higher risk for it, associated with a high mortality rate. Beside AF, there are several other risk factors which influence the risk of stroke. Stroke risk calculator can be used to assess the risk of patient having a stroke. The most endangered group of patients with AF are those who have already suffered from cerebrovascular event. The only effective medication for prevention of stroke due to AF had been the application of vitamin K antagonists (VKA) which considerably decrease the rate of ischaemic event in a patient with AF providing that the INR is in the therapeutic range. VKA have several limitations of use in clinical practice and the fear of bleeding complications results an underusing of these drugs. Only 50% of all patients treated with VKA reaches the therapeutic range of INR. The breakthrough of prevention of stroke in recent years is undisputedly the coming out of novel oral anticoagulants (NOACs, thrombin and Xa-factor inhibitors). Recent studies suggest that these novel drugs prove the same efficacy as VKA drugs, furthermore dabigatran in a dose of 2×150 mg or apixaban in 2×5mg was statistically superior to warfarin in the prevention of stroke. NOACs have shown a large reduction in intracranial hemorrhage compared with warfarin. They are given as a fixed dose and do not require persistent monitoring making them much more convenient. NOACs at guidelines of European Society of Cardiology act as a preferable drugs in case of ischaemic stroke with AF. Probably the extended use of NOACs in clinical practice will be the mainstream of stroke prevention in the future.]

Clinical Neuroscience

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

MIROLOVICS Csaba, PAPP Judit, ZSUGA Dániel

[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.]

Clinical Neuroscience

[Systemic thrombolysis after the administration of idarucizumab in acute ischemic stroke]

PÁSZTOR Máté, BERECZKI Dániel, SZAKÁCS ZOLTÁN, MAY Zsolt

[Introduction - Expanding indications have resulted in an increasing number of patients taking novel oral anticoagulants, posing a major treatment dilemma in acute ischemic stroke. Case presentation - We present a successful intravenous thrombolysis in a dabigatran-treated patient with acute ischemic stroke after the administration of idarucizumab. Discussion - According to current guidelines, systemic thrombolysis is contraindicated under treatment with novel oral anticoagulants (taken within 48 hours). In this scenario, idarucizumab offers a solution by reversing the anticoagulant effect of dabigatran. Conclusion - Although there have only been case reports published so far, the dabigatran-antidote idarucizumab seems to give new therapeutic opportunities in the treatment of acute ischemic stroke.]

Lege Artis Medicinae

[Dabigatran: a new oral anticoagulant agent for the prevention of stroke and systemic embolism in nonvalvular atrial fibrillation]

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.]