Antal Tibold

Aspirin Resistance : Focus on Clinical Endpoints

Introduction: Via its antiplatelet effect, aspirin reduces the odds of an arterial thrombotic event in high-risk patients by approximately 25%. However, 10% to 20% of patients with an arterial thrombotic event who are treated with aspirin have a recurrent arterial thrombotic event during long-term follow-up. Nevertheless, the effectiveness of aspirin has been questioned by the emergence of the concept of aspirin resistance, which has been introduced as an explanation of the fact that a considerable proportion of patients treated with aspirin exhibit normal platelet function. Objectives and Methods: We systematically reviewed all available evidence till March 2008 on prevalence of aspirin resistance and its association with clinical outcome. We also collected articles showing the possible way of treatment. Conclusion: Analyzing the data of different laboratory methods aspirin resistance seems to be associated with poor clinical outcome, although currently no standardized or widely accepted definition of aspirin resistance exists. The widely used laboratory methods might not be comparable with each other; therefore, specific treatment recommendations for patients who exhibit high platelet reactivity during aspirin therapy or who have poor platelet inhibition by aspirin are not established.

Platelet Aggregometry Testing: Molecular Mechanisms, Techniques and Clinical Implications.

Platelets play a fundamental role in normal hemostasis, while their inherited or acquired dysfunctions are involved in a variety of bleeding disorders or thrombotic events. Several laboratory methodologies or point-of-care testing methods are currently available for clinical and experimental settings. These methods describe different aspects of platelet function based on platelet aggregation, platelet adhesion, the viscoelastic properties during clot formation, the evaluation of thromboxane metabolism or certain flow cytometry techniques. Platelet aggregometry is applied in different clinical settings as monitoring response to antiplatelet therapies, the assessment of perioperative bleeding risk, the diagnosis of inherited bleeding disorders or in transfusion medicine. The rationale for platelet function-driven antiplatelet therapy was based on the result of several studies on patients undergoing percutaneous coronary intervention (PCI), where an association between high platelet reactivity despite P2Y12 inhibition and ischemic events as stent thrombosis or cardiovascular death was found. However, recent large scale randomized, controlled trials have consistently failed to demonstrate a benefit of personalised antiplatelet therapy based on platelet function testing.

Statintherapy in the primary and the secondary prevention of ischaemic cerebrovascular diseases

INTRODUCTION Stroke is a major public health problem. It is the third leading cause of death worldwide and results in hospital admissions, morbidity, and long-term disability. Despite the inconsistent or weak association between cholesterol and stroke, statins can reduce the incidence of stroke in high-risk populations and in patients with a stroke or transient ischaemic attack. METHODS The aim of our study was to review the efficacy of statin therapy in both primary and secondary stroke prevention. We also reviewed the effectiveness and cost-effectiveness among different statins and we also reviewed the possible effect of treatment added to statin monotherapy. RESULTS There is evidence that statin therapy in both primary and secondary prevention significantly reduces subsequent major coronary events but only marginally reduces the risk of stroke recurrence. There is no clear evidence of beneficial effect from statins in those with previous haemorrhagic stroke and it is unclear whether statins should be started immediately post stroke or later. There is a pressing need for direct evidence, from head-to-head trials, to determine whether individual statins provide differing protection from clinically important events in stroke prevention. It is possible that combinations of lipid-lowering agents did not improve clinical outcomes more than high-dose statin monotherapy, although clinical trials are still ongoing.

Enhancement of Organ Regeneration in Animal Models by a Stem Cell-Stimulating Plant Mixture

Adult stem cells play an important role in the regeneration of damaged organs. Attempts have already been made to enhance stem cell production by cytokines, in order to increase the improvement of cardiac functions after myocardial infarction. In our present study we investigated the possibility whether instead of cytokine injection dietary stimulation of stem cell production accelerates the organ regeneration in animals. A dietary supplement, Olimpiq StemXCell (Crystal Institute Ltd., Eger, Hungary), containing plant extracts (previously proved to increase the number of circulating CD34(+) cells) was consumed in human equivalent doses by the experimental animals. In the first experiment carbon tetrachloride was applied to CBA/Ca mice, to induce liver damage, and liver weights between StemXCell-fed and control animals were compared 10 days after the treatment. In the second model experimental diabetes was induced in F344 rats by alloxan. Blood sugar levels were measured for 5 weeks in the control and StemXCell-fed groups. The third part of the study investigated the effect of StemXCell on cardiac functions. Eight weeks after causing a myocardial infarction in Wistar rats by isoproterenol, left ventricular ejection fraction was determined as a functional parameter of myocardial regeneration. In all three animal models StemXCell consumption statistically significantly improved the organ regeneration (relative liver weights, 4.78 +/-0.06 g/100 g vs. 4.97 +/- 0.07 g/100 g; blood sugar levels at week 5, 16 +/- 1.30 mmol/L vs. 10.2 +/- 0.92 mmol/L; ejection fraction, 57.5 +/- 2.23 vs. 68.2 +/- 4.94; controls vs. treated animals, respectively). Our study confirms the hypothesis that dietary enhancement of stem cell production may protect against organ injuries and helps in the regeneration.

Gender differences in hemorheological parameters and in in vitro platelet aggregation in acetylsalicylic acid and clopidogrel treated vascular patients

BACKGROUND Sex-specific response to antiplatelet medications have been reported in several previous studies. OBJECTIVE We investigated a possible connection between gender differences in hemorheological parameters and in vitro platelet aggregation in vascular patients treated with widely used antiplatelet agents. METHODS In vitro platelet aggregation was assessed in 2687 patients treated with 100 mg acetylsalicylic acid (ASA), 1047 patients treated with 75 mg clopidogrel and 311 patients on dual antiplatelet therapy (100 mg aspirin and 75 mg clopidogrel) according to the method of Born. In subgroups of patients fibrinogen concentration, whole blood and plasma viscosity, red blood cell aggregation and hematocrit were simultaneously measured. The subjects were divided into groups according to their gender. RESULTS ADP induced platelet aggregation was significantly higher in women in the case of ASA treatment (p<0.001). No gender differences could be observed in platelet function in patients treated with clopidogrel or on dual antiplatelet therapy. Hematocrit and whole blood viscosity were significantly higher in men in all groups (p<0.001), while no significant gender differences were observed in red blood cell aggregation indices in either group. Fibrinogen concentration was significantly higher in women than in men among patients treated with 100 mg ASA (p<0.05), but not in the other groups. CONCLUSIONS Significantly higher fibrinogen concentration found in aspirin treated women than men may play a role in higher ADP induced platelet aggregation. Gender differences in response to monotherapy suggest that benefits from combination therapy may be greater in females. The clinical relevance of higher ADP induced platelet aggregation in women treated with ASA needs further investigation.

Clopidogrelrezisztencia vizsgálata cerebrovascularis betegségben – egyéves utánkövetés@@@Clopidogrel resistance in cerebrovascular disease – results of one-year follow-up

Bevezetes: Korabban mar leirtak a clopidogrelkezeles hatekonysagat akut ischaemias cerebrovascularis esemenyen atesett betegek koreben rovid tavon. Celkitűzes: A szerzők celja a betegek egyeves utankovetesi adatainak bemutatasa. Modszer: A vizsgalatban 100, akut stroke-on/tranziens ischaemias attakon atesett beteg vett reszt. A betegek az első 48 oraban aszpirinkezelesben, majd clopidogrelkezelesben reszesultek. A kezeles hatekonysagat a gyogyszeres terapia bevezeteset kovetően 7 es 28 nap, majd 3, 6 es 12 honap utan ellenőriztek. A betegeket ket csoportra osztottak optikai aggregometrias leletuk alapjan (clopidogrelerzekeny es -rezisztens). A ket csoport kockazati profiljat, gyogyszereit, laboratoriumi parametereit es a klinikai kimenetelt elemeztek. Eredmenyek: A clopidogrelkezeles eseteben szoros osszefugges mutatkozott az aktualis vernyomas, a vercukor- es verzsiranyagcsere-parameterek, az ultraszenzitiv C-reaktiv protein szintje es a thrombocytaaggregacios ertekek kozott (p<0,05). Erelyes szekunder prevencios kezeles hatasara a fent jelzett parameterek normalizalasaval parhuzamosan a thrombocytaaggregacio-gatlo kezeles hatekonysaga is novelhető volt, hosszabb tavon rezisztens beteg nem volt. Az egyeves utankovetes soran a kezdetben rezisztens betegek eseteben tobb volt a vascularis esemenyek aranya (4 kezdeti clopidogrelerzekeny [4,5%] vs. 2 kezdeti clopidogrelrezisztens [18,1%], p<0,01), ugyanakkor a rezisztencia jelensege nem bizonyult a kesőbbi kedvezőtlen kimenetel fuggetlen kockazati faktoranak a multivariacios analizis soran. Kovetkeztetesek: Jelen vizsgalat eredmenyei alapjan igen komolyan felvetődik az erelyes szekunder prevencios kezeles szerepe a thrombocytaaggregacio-gatlo terapia hatekonysaganak hattereben. Orv. Hetil., 2015, 156(2), 53–59.

Clopidogrelrezisztencia vizsgálata cerebrovascularis betegségben – egyéves utánkövetés

Bevezetes: Korabban mar leirtak a clopidogrelkezeles hatekonysagat akut ischaemias cerebrovascularis esemenyen atesett betegek koreben rovid tavon. Celkitűzes: A szerzők celja a betegek egyeves utankovetesi adatainak bemutatasa. Modszer: A vizsgalatban 100, akut stroke-on/tranziens ischaemias attakon atesett beteg vett reszt. A betegek az első 48 oraban aszpirinkezelesben, majd clopidogrelkezelesben reszesultek. A kezeles hatekonysagat a gyogyszeres terapia bevezeteset kovetően 7 es 28 nap, majd 3, 6 es 12 honap utan ellenőriztek. A betegeket ket csoportra osztottak optikai aggregometrias leletuk alapjan (clopidogrelerzekeny es -rezisztens). A ket csoport kockazati profiljat, gyogyszereit, laboratoriumi parametereit es a klinikai kimenetelt elemeztek. Eredmenyek: A clopidogrelkezeles eseteben szoros osszefugges mutatkozott az aktualis vernyomas, a vercukor- es verzsiranyagcsere-parameterek, az ultraszenzitiv C-reaktiv protein szintje es a thrombocytaaggregacios ertekek kozott (p<0,05). Erelyes szekunder prevencios kezeles hatasara a fent jelzett parameterek normalizalasaval parhuzamosan a thrombocytaaggregacio-gatlo kezeles hatekonysaga is novelhető volt, hosszabb tavon rezisztens beteg nem volt. Az egyeves utankovetes soran a kezdetben rezisztens betegek eseteben tobb volt a vascularis esemenyek aranya (4 kezdeti clopidogrelerzekeny [4,5%] vs. 2 kezdeti clopidogrelrezisztens [18,1%], p<0,01), ugyanakkor a rezisztencia jelensege nem bizonyult a kesőbbi kedvezőtlen kimenetel fuggetlen kockazati faktoranak a multivariacios analizis soran. Kovetkeztetesek: Jelen vizsgalat eredmenyei alapjan igen komolyan felvetődik az erelyes szekunder prevencios kezeles szerepe a thrombocytaaggregacio-gatlo terapia hatekonysaganak hattereben. Orv. Hetil., 2015, 156(2), 53–59.

[Clopidogrel resistance in cerebrovascular disease -- results of one-year follow-up].

Bevezetes: Korabban mar leirtak a clopidogrelkezeles hatekonysagat akut ischaemias cerebrovascularis esemenyen atesett betegek koreben rovid tavon. Celkitűzes: A szerzők celja a betegek egyeves utankovetesi adatainak bemutatasa. Modszer: A vizsgalatban 100, akut stroke-on/tranziens ischaemias attakon atesett beteg vett reszt. A betegek az első 48 oraban aszpirinkezelesben, majd clopidogrelkezelesben reszesultek. A kezeles hatekonysagat a gyogyszeres terapia bevezeteset kovetően 7 es 28 nap, majd 3, 6 es 12 honap utan ellenőriztek. A betegeket ket csoportra osztottak optikai aggregometrias leletuk alapjan (clopidogrelerzekeny es -rezisztens). A ket csoport kockazati profiljat, gyogyszereit, laboratoriumi parametereit es a klinikai kimenetelt elemeztek. Eredmenyek: A clopidogrelkezeles eseteben szoros osszefugges mutatkozott az aktualis vernyomas, a vercukor- es verzsiranyagcsere-parameterek, az ultraszenzitiv C-reaktiv protein szintje es a thrombocytaaggregacios ertekek kozott (p<0,05). Erelyes szekunder prevencios kezeles hatasara a fent jelzett parameterek normalizalasaval parhuzamosan a thrombocytaaggregacio-gatlo kezeles hatekonysaga is novelhető volt, hosszabb tavon rezisztens beteg nem volt. Az egyeves utankovetes soran a kezdetben rezisztens betegek eseteben tobb volt a vascularis esemenyek aranya (4 kezdeti clopidogrelerzekeny [4,5%] vs. 2 kezdeti clopidogrelrezisztens [18,1%], p<0,01), ugyanakkor a rezisztencia jelensege nem bizonyult a kesőbbi kedvezőtlen kimenetel fuggetlen kockazati faktoranak a multivariacios analizis soran. Kovetkeztetesek: Jelen vizsgalat eredmenyei alapjan igen komolyan felvetődik az erelyes szekunder prevencios kezeles szerepe a thrombocytaaggregacio-gatlo terapia hatekonysaganak hattereben. Orv. Hetil., 2015, 156(2), 53–59.