Clinical Neuroscience

[Rivaroxaban in prevention of stroke in patients with atrial fibrillation]


NOVEMBER 20, 2012

Clinical Neuroscience - 2012;65(11-12)

[Atrial fibrillation (AF) is well established risk factor for cardioembolic stroke. With thromboprophylatic treatment we can reduce the risk of stroke in patients with AF. Oral vitamin K antagonists (VKA) such as warfarin and acenocoumarol are effective for stroke prevention in patients with atrial fibrillation. VKAs are associated with several limitations including very narrow therapeutic range, several factors (diet, drugs, alcohol consumption) affecting the effect of VKA and excessive bleeding may occur if INR value not controlled successfully. New oral anticoagulant direct Xa factor inhibitor rivaroxaban has a good therapeutic efficacy in prevention (primary and secondary) of stroke in AF patients. Its advantages are including no need for monitoring, fixed oral dose, not affected by meal, age and body weight, all of them can improve patient adherence. In ROCKET AF trial in patients with AF, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group.]



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[Clinical significance of the cardiovascular effects of fingolimod treatment in multiple sclerosis]


[Fingolimod is a sphingosine-1 phosphate receptor modulator, which is effective in the treatment of severe relapsingremitting form of multiple sclerosis. Once daily oral use of fingolimod decreased the annualized relapse rate, inflammatory brain lesion activity and the rate of brain atrophy compared both to placebo and intramuscular administered interferon beta-1a. The drug targets the cardiovascular system as well via sphingosine- 1 phosphate receptors. After initiation of fingolimod therapy transient sinus bradycardia and slowing of the atrioventricular conduction develops. The onset of the effect is as early as 1 hour post administration, while heart rate and conduction normalized in 24 hours in most of the cases. According to the clinical trials symptomatic bradycardia developed in 0.5% of the cases, responding to the appropriate therapy. The incidence of Mobitz I type II atrioventricular blocks and blocks with 2:1 atrioventricular conduction was 0.2% and 0.1%, respectively. All of these cardiovascular events showed regression during observation and no higher degree atrioventricular blocks were detected at the approved therapeutic dose. Following the first dose effect, fingolimod had a moderate hypertensive effect on long-term. For the safety of fingolimod treatment detailed cardiovascular risk stratification of all patients, adequate patient monitoring after the first dose and competency in treating the possible side effects is necessary. In patients with increased cardiovascular risks, treatment should be considered only if anticipated benefits outweigh potential risks and extended monitoring is required.]

Clinical Neuroscience

[Dear Colleagues!]

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Clinical Neuroscience

[Vinpocetin in neurological diseases]

SZAPÁRY László, KÉSMÁRKY Gábor, TÓTH Kálmán, MISNYOVSZKY Melinda, TÓTH Tímea, BALOGH Ágnes, NAGY Krisztián, NÉMETH György, FEHÉR Gergely

[Introduction - Stroke is the third leading cause of death worldwide (following cardiovascular and cancer mortality) and associated with serious disability for the vast majority of patients. There is no salvage therapy for irreversibly damaged brain areas, improving the circulation of the surrounding hypoperfused territories may be associated with benefitial clinical states. Cerebral hypoperfusion may play a role in the pathogenesis of other kind of neurological diseases, improvement of global circulation may have a preventive effect on these conditions. Aims - The aim of our study was to review the experimental and clinical articles focusing on the role of vinpocetin in different neurological conditions. Results - Vinpocetin appears to have several different mechanisms of action that allow for its antiinflammatory, antioxidant, vasodilating, antiepileptic and neuroprotective activities in experimental conditions. On the other hand, several meta-analysis of the existing studies in acute stroke examining short and long term fatality rates with vinpocetin was unable to assess efficacy. In chronic cerebrovascular patients, vinpocetin improves impaired hemorheological variables, has significant vasodilating properties, improves endothelial dysfunction, neuroimaging studies showed selective increase in cerebral blood flow and cerebral metabolic rate, all of which are potentially beneficial in cerebrovascular disease and may improve cognitive functions. Summary - Based on the above mentioned results vinpocetin plays an important role both in basic research and in clinical management of different neurological diseases.]

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[Blood pressure management for stroke prevention and in the acute stroke. The new guideline of European Society of Hypertension (ESH, 2018), European Society of Cardiology and Hungarian Society of Hypertension (HSH, 2018)]

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[Hypertension is the leading modifiable risk factor for stroke. Its prevalence amongst stroke patient is about 60-70% and the benefit of blood pressure (BP) lowering therapy on stroke risk reduction is well established. However the optimal BP targets for preventing stroke and reducing stroke consequences have been controversial. The new European (ESC/ESH) and Hungarian (HSH) hypertension guideline published in 2018 highlighted the primary and secondary prevention of stroke and the BP management in the acute stroke care as well. According results from ACCORD, SPRINT, HOPE-3, and other metaanalysis the systolic blood pressure (SBP) lowering < 120 mmHg has not favourable effect, thus in hypertensive patients < 65 years the SBP should be lowered to a BP range of 120-129 mmHg. In older patients ≥ 65 years the SBP should be targeted to a BP range of 130-139 mmHg (IA). In patients with acute intracerebral haemorrhage careful acute BP lowering with iv. therapy, to <180 mmHg should be considered only in case of SBP ≥ 220 mmHg (IIaB). In patients with acute ischaemic stroke who are eligible for iv. thrombolysis, BP should be carefully lowered and maintained to < 180/105 mmHg for at least the first 24 h after thrombolysis (IIaB). If the patient is not eli gible for lysis and BP ≤ 220/110 mmHg, routine BP lowering drug therapy is not recommended inside 48-72 h (IA). In patients with markedly elevated BP > 220/110 mmHg who do not receive fibrinolysis, drug therapy may be considered, based on clinical judgement, to reduce BP by 15% during the first 24 h after the stroke onset (IIbC). After 72 h of acute stroke in case of hypertensive patients < 65 years the SBP should be lowered to a BP range of 120-129 mmHg (IIaB). In older patients ≥ 65 years the SBP should be targeted to a BP range of 130-139 mmHg (IA). If BP < 140/90 mmHg after stroke, the BP lowering should be considered (IIbA). It is recommended to initiate an antihypertensive treatment with combination, preferably single pill combination of renin-angiotensin system blockers plus a calcium channel blocker and/or a thiazide like diuretics (IA). Lowering SBP < 120 mmHg is not recommended due to advers events regardless of age and type of stroke either in primary or secondary stroke prevention.]

Clinical Oncology

[The role of the microbiome in the etiology and treatment of neoplastic diseases]

SCHWAB Richárd, BACSUR Emese, TORDAI Attila, PETÁK István

[Experimental data on the role of the microbiome in the onset and progression of infl ammatory diseases and cancer have been accumulated for years. An important milestone in this respect was the discovery that APC mutant mice in sterile conditions do not develop colon cancer of the FAP type. The direct role of the Enterobacteriaceae and Fusobacteriaceae bacterial families were also shown in the pathomechanism of the same experimental model. The toxic effect of chemotherapy on the gut fl ora has been well documented, but it may very well be that this putative side effect is part of the effi cacy, primarily in the case of adjuvant chemotherapy. The fi rst reproducible methods of microbiome molecular diagnostics are already available today. In addition to standard large clinical studies, we can increasingly rely on evidence of molecular pathomechanism and „real-world” clinical experience in the clinical interpretation of the microbiome. The overview summarizes the results of the fi eld research and its translation possibilities in terms of routine clinical practice.]

Clinical Neuroscience

[Excerpts of achievements of pharmaceutical cerebro-vascular protection, with especial regard to the statins]


[Despite that hypercholesterinemia is not a risk factor of stroke, treatment with statins is able to reduce these events in a clinically relevant degree. Intervention trials suggest that while for primary prevention, statins are effective in conventional dose, after stroke or TIA this is true only if LDL-cholesterol is reduced below 1,8 mmol/L. To reach this goal, usually intensive antilipid treatment is necessary. There are studies showing beneficial impacts of other lipid drugs, beyond statins, i.e. fibrates and fish oil (among the settings of primary, and secondary preventions, respectively). Against cerebro-vascular events, pleitropic effects of some antihypertensive and antidiabetic medications can also be established.]


[Vitamin D treatment: hormone therapy for patients who need it or simply a supplementation for everyone?]


[Various medical associations issue different recommendations for the prevention and treatment of vitamin D deficiency. These significant differences are partly explained by the different definition of normal vitamin D level and the use of completely different mathematical models to predict the increase in vitamin D level as a response to therapy. According to the Institute of Medicine (IOM), the target vitamin D level is 20 ng/ml, whereas the Endocrine Society (ES) recommends 30 ng/m as the miminum target value. According to the ES, a 1 ng/ml increase of vitamin D level can be reached by a daily intake of 100 NE, while the IOM recommends 3.6 ng/ml. Moreover, the IOM states that the effect of therapy on serum level is nonlinear. These differences show that the ES and IOM have different views on the risk of adverse effects. The IOM recommends 400 IU vitamin D daily for children younger than 1 year, 800 IU for those above 70 years and 600 IU/per day for everyone else. The ES recommend 400-1000 IU daily for all infants and 1500- 2000 IU for adults. Screening, however, is not recommended by either society. To decrease uncertainty concerning the side effects of higher-dose vitamin D treatment, it is important to understand, use and support the function of the pharmacovigilance system of the pharmaceutical industry that manufactures and markets various (prescription, over-the-counter) preparations. This is what the author aims to highlight in the second part of this article. Using this system, both the doctor and the patient can help support and accept the justification of higher-dose vitamin D therapy.]