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SPIRIT Checklists with recommended items to address in a clinical trial protocol and related documents. (DOC 122 kb)
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Introduction Knowledge of the implementation gap would facilitate the use of intravenous thrombolysis in stroke, which is still low in many countries. The study was conducted to identify national implementation targets for the utilisation... more
Introduction Knowledge of the implementation gap would facilitate the use of intravenous thrombolysis in stroke, which is still low in many countries. The study was conducted to identify national implementation targets for the utilisation and logistics of intravenous thrombolysis. Material and Method Multicomponent interventions by stakeholders in health care to optimise prehospital and hospital management with the goal of fast and accessible intravenous thrombolysis for every candidate. Implementation results were documented from prospectively collected cases in all 45 stroke centres nationally. The thrombolytic rate was calculated from the total number of all ischemic strokes in the population of the Czech Republic since 2004. Results Thrombolytic rates of 1.3 (95%CI 1.1 to 1.4), 5.4 (95%CI 5.1 to 5.7), 13.6 (95%CI 13.1 to 14.0), 23.3 (95%CI 22.8 to 23.9), and 23.5% (95%CI 23.0 to 24.1%) were achieved in 2005, 2009, 2014, 2017, and 2018, respectively. National median door-to-needl...
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Research Interests: Medicine and Thrombolysis
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Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) underestimates clinical severity in posterior circulation stroke and patients presenting with low NIHSS may be considered ineligible for reperfusion therapies.... more
Background and Purpose: The National Institutes of Health Stroke Scale (NIHSS) underestimates clinical severity in posterior circulation stroke and patients presenting with low NIHSS may be considered ineligible for reperfusion therapies. This study aimed to develop a modified version of the NIHSS, the Posterior NIHSS (POST-NIHSS), to improve NIHSS prognostic accuracy for posterior circulation stroke patients with mild-moderate symptoms. Methods: Clinical data of consecutive posterior circulation stroke patients with mild-moderate symptoms (NIHSS <10), who were conservatively managed, were retrospectively analyzed from the Basilar Artery Treatment and Management registry. Clinical features were assessed within 24 hours of symptom onset; dysphagia was assessed by a speech therapist within 48 hours of symptom onset. Random forest classification algorithm and constrained optimization were used to develop the POST-NIHSS in the derivation cohort. The POST-NIHSS was then validated in a...
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Klinicke situace vyžadujici monitoraci nových oralnich antikoagulancii (NOAC) jsou: přitomnost krvaceni, renalni insuficience, podezřeni na předavkovani nebo u ischemicke cevni mozkove přihody, kdy se zvažuje trombolýza. Běžně dostupne... more
Klinicke situace vyžadujici monitoraci nových oralnich antikoagulancii (NOAC) jsou: přitomnost krvaceni, renalni insuficience, podezřeni na předavkovani nebo u ischemicke cevni mozkove přihody, kdy se zvažuje trombolýza. Běžně dostupne koagulacni testy, jako např. aPTT, TT ci PT mohou, ale nemusi být pro monitoraci NOAC dostacujici. Lekaři rozhodujici např. o trombolýze musi znat interpretaci naměřených hodnot, ktera může být odlisna u pacientů uživajicich dabigatran, rivaroxaban nebo apixaban. Navic, pro NOAC jsou použivany specialni testy, např. Hemoclot ci standardizovane anti-Xa testy, u kterých je opět důležite znat spravnou interpretaci. Tento clanek proto přinasi přehled o vhodných koagulacnich testech pro jednotliva NOAC a shrnuje přehledným způsobem ve formě tabulek dostupna data o interpretaci naměřených výsledků tak, aby měl klinik okamžitou informaci napřiklad o možnosti podat trombolýzu.
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OBJECTIVE: To evaluate safety and efficacy of percutaneous transluminal angioplasty (PTA) and mechanical embolectomy (ME) in the treatment of acute middle cerebral artery occlusion (MCAo), including bridging therapy (intravenous... more
OBJECTIVE: To evaluate safety and efficacy of percutaneous transluminal angioplasty (PTA) and mechanical embolectomy (ME) in the treatment of acute middle cerebral artery occlusion (MCAo), including bridging therapy (intravenous thrombolysis [IVT] with subsequent endovascular treatment [EVT]). BACKGROUND: In the treatment of acute MCAo, IVT has only limited effectiveness, while EVT represents an alternative treatment method. EVT comprises also “older” PTA and “up-to-date” ME. Nevertheless, only limited data with controversial results is available regarding the comparison of their safety and efficacy (including bridging therapy). DESIGN/METHODS: In the retrospective study, data from the national multicenter registry of cerebral mechanical recanalizations was analyzed. The set consisted of 126 acute ischemic stroke patients (64 males; mean age 68.0 ± 13.3 years) with radiologically confirmed MCAo. Following data was collected: baseline characteristics, risk factors, pre-event treatmen...
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Time is of the essence to prevent brain damage in the context of acute ischaemic stroke, yet most patients do not receive specialist care or early reperfusion therapy in the setting of acute ischaemic stroke. In order to increase the... more
Time is of the essence to prevent brain damage in the context of acute ischaemic stroke, yet most patients do not receive specialist care or early reperfusion therapy in the setting of acute ischaemic stroke. In order to increase the number of patients treated in stroke-ready hospitals and optimise the quality of treatment in all existing stroke centres, the ANGELS (Acute Networks Striving for Excellence in Stroke) Initiative was established in 2015. This article summarizes the experiences of different countries in stroke unit planning and quality monitoring presented at a symposium at the 4th European Stroke Organization Conference (ESOC) in May 2018 in Gothenburg, Sweden.
Embolic stroke of undetermined source (ESUS) is a subset of cryptogenic stroke. Recurrence rates are high following ESUS and the optimal treatment to reduce the risk of recurrent stroke depends on the pathophysiology of the index stroke.... more
Embolic stroke of undetermined source (ESUS) is a subset of cryptogenic stroke. Recurrence rates are high following ESUS and the optimal treatment to reduce the risk of recurrent stroke depends on the pathophysiology of the index stroke. Because of the composition of emboli, anticoagulants may be a better treatment option than antiplatelet therapy in secondary stroke prevention. This article reviews recent and ongoing clinical trials evaluating antithrombotic treatments in the setting of ESUS, examines differences among the trials, and discusses the implications of anticoagulation in ESUS.
The aim: Chronic intracranial hypertension is present with the prevalence of 30–40% in syndrome craniosynostoses, of 12–20% in monosynostoses. This study aim was to establish whether there exists relation between the values of lumbar... more
The aim: Chronic intracranial hypertension is present with the prevalence of 30–40% in syndrome craniosynostoses, of 12–20% in monosynostoses. This study aim was to establish whether there exists relation between the values of lumbar cerebrospinal fluid pressure in children with scaphocephaly and flow indices at the examinations using transcranial doppler sonography (TCD), and to compare preand postoperative results of TCD investigations. Method: Twenty-two children with scaphocephaly underwent, besides routine pre-operative examinations, the manometric measurements of the lumbar liquor pressures and TCD investigation that was repeated 7–8 days after the surgery. A paired t-test was used for the comparison of preand post-operative flow indices. Spearman ́s correlation coefficient was applied for establishing the correlation of the lumbar pressure values and TCD flow indices. Results: Neither brain CT nor cranial roentgenograms showed pre-operative signs of chronic intracranial hyper...
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Souhrn V přehledove praci jsou shrnuty soucasne poznatky o vlivu cevnich změn mozku a jejich rizikových faktorů na rozvoj a průběh Alzheimerovy choroby. Je diskutovano o casove souvislosti a vzajemne interakci cevnich a... more
Souhrn V přehledove praci jsou shrnuty soucasne poznatky o vlivu cevnich změn mozku a jejich rizikových faktorů na rozvoj a průběh Alzheimerovy choroby. Je diskutovano o casove souvislosti a vzajemne interakci cevnich a neurohistopatologických změn pro chorobu typických. Jsou popsany jednotlive neurozobrazovaci metody detekujici cevni změny mozku; nalezy těchto vysetřeni jsou korelovany s dopadem na kognitivni funkce ci riziko vzniku Alzheimerovy choroby. Nejcastějsimi strukturalnimi změnami provazejicimi cevni patologii jsou změny bile hmoty (white matter lesions) a drobna mozkova petechialni krvaceni (cerebral microbleeds) zobrazitelne pomoci MR. Funkcni změny mozkove perfuze mapuje perfuzni SPECT nebo neurosonologie. Bližsi specifikace cevnich změn u pacientů s Alzheimerovou chorobou se může stat významným parametrem pro predikci rychlosti progrese onemocněni u pacientů s mirnou kognitivni poruchou nebo pocatecni demenci. Rovněž může přispět při stanoveni rizika rozvoje Alzheimer...
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Introduction: Dabigatran is direct thrombin inhibitor approved in the prevention of stroke in patients with atrial fibrillation. It was shown in the RELY trial substudy that genetic variants could ...
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Alemtuzumab as a treatment of highly active multiple sclerosis causes a rapid decrease in inflammatory activity due the lysis of immune cells. Subsequent cytokine release determines the infusion-associated reaction that is a frequent... more
Alemtuzumab as a treatment of highly active multiple sclerosis causes a rapid decrease in inflammatory activity due the lysis of immune cells. Subsequent cytokine release determines the infusion-associated reaction that is a frequent adverse event of alemtuzumab treatment. Recently, serious cardiovascular and thrombotic adverse reactions following alemtuzumab infusion have been described. In our study, the dynamics of coagulation parameters were analyzed in 13 multiple sclerosis patients treated with alemtuzumab. An immediate, significant increase in the level of D-dimer was observed after the first administration of alemtuzumab. This observation provides evidence of coagulation activation and the potential risk of thrombotic complications with this therapy. Prophylactic low molecular weight heparin pretreatment maybe considered in patients receiving alemtuzumab.
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BACKGROUND Cerebral microangiopathy in Alzheimer's disease (AD) causes chronic hypoperfusion and probably accelerates neurodegenerative changes. OBJECTIVE We hypothesize microvascular impairment could be present already in mild... more
BACKGROUND Cerebral microangiopathy in Alzheimer's disease (AD) causes chronic hypoperfusion and probably accelerates neurodegenerative changes. OBJECTIVE We hypothesize microvascular impairment could be present already in mild cognitive impairment (MCI) and can be revealed using transcranial color-coded sonography (TCCS) and the breath-holding maneuver. METHODS Three groups of subjects (AD in the stage of dementia, MCI, and cognitively normal controls) with detailed neuropsychological testing and low cerebrovascular burden (no history of stroke, no intra- or extracranial artery stenoses, and no severe vascular lesions on brain MRI), underwent a TCCS assessment of peak systolic (PSV), mean flow (MFV), and end diastolic velocities (EDV) and resistance and pulsatility indices (RI, PI) in large intracranial vessels bilaterally. Cerebrovascular reserve capacity was assessed using the breath-holding index (BHI) in middle cerebral artery (MCA) bilaterally. The ultrasound parameters were compared between the groups, correlated with neuropsychological tests, and compared between amnestic and non-amnestic MCI subtypes. RESULTS Fourteen AD (3 males, 67.9±11.1 years, MMSE 18.0±4.6), 24 MCI (13 males, 71.9±7.3 years, MMSE 28.0±1.6), and 24 risk factor-matched controls (14 males, 67.8±6.4 years, MMSE 29.1±1.2) were enrolled. Significant differences were found between AD and controls in MFV, EDV, RI, PI in right MCA after breath holding, in PSV, MFV, EDV in left MCA after breath holding, and in BHI on the left side. The left BHI correlated positively with verbal memory test. CONCLUSION Results show decreased cerebrovascular reserve capacity in AD as a sign of impaired cerebral hemodynamic status without severe underlying atherosclerosis. This can be identified using TCCS and BHI.
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Warfarin treatment is commonly started with a fixed loading dose that might be associated with an increased risk of bleeding. An individual maintenance dose can then be estimated based on a pharmacogenetic algorithm. Starting treatment... more
Warfarin treatment is commonly started with a fixed loading dose that might be associated with an increased risk of bleeding. An individual maintenance dose can then be estimated based on a pharmacogenetic algorithm. Starting treatment with the estimated dose implies a longer time to reach the therapeutic range. Our goal was to compare the safety and efficacy of initiating warfarin treatment with a loading dose guided by pharmacogenetics versus a maintenance dose. The primary endpoint was time in the therapeutic range (TTR) in the first 10 days of treatment. Secondary endpoints were time to the first international normalized ratio (INR) in therapeutic range (2.0–3.0) and occurrence of serious adverse events. Consenting cardioembolic stroke patients were genotyped for CYP2C9 (cytochrome P450 2C9 gene) and VKORC1 (vitamin K epoxide reductase complex, subunit 1 gene) polymorphisms and a maintenance warfarin dose was estimated. Patients were randomized into two groups. The loading dose group (LDG) patients received twice the estimated dose in the first 2 days of treatment. The maintenance dose group (MDG) patients received the estimated dose directly from day one. The TTR in the first 10 days was significantly higher in the LDG than in the MDG (50.5% vs. 38.3%, p = 0.003). The time to the first INR in this range was significantly shorter in the LDG (5.24 vs. 7.3 days). There were no significant differences in the INR above this range or serious adverse events. Warfarin loading dose guided by pharmacogenetics after recent cardioembolic stroke improved the efficacy of warfarin initiation without increasing the risk of adverse events.
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Randomized clinical trials have proven mechanical thrombectomy (MT) to be a highly effective and safe treatment in acute stroke. The purpose of this study was to compare neurothrombectomy data from the Czech Republic (CR) with data from... more
Randomized clinical trials have proven mechanical thrombectomy (MT) to be a highly effective and safe treatment in acute stroke. The purpose of this study was to compare neurothrombectomy data from the Czech Republic (CR) with data from the HERMES meta-analysis. Available nationwide data for the CR from 2016 from the Safe Implementation of Treatments in Stroke-Thrombectomy (SITS-TBY) registry for patients with terminal internal carotid artery (ICA) and/or middle cerebral artery (MCA) occlusions were compared with data from HERMES. CR and HERMES patients were comparable in age, sex, and baseline National Institutes of Health Stroke Scale scores. From a total of 1053 MTs performed in the CR, 845 (80%) were reported in the SITS-TBY. From these, 604 (72%) were included in this study. Occlusion locations were as follows (CR vs HERMES): ICA 22% versus 21% (P=0.16), M1 MCA 62% versus 69% (P=0.004), and M2 MCA 16% versus 8% (P<0.0001). Intravenous thrombolysis was given to 76% versus 83%...
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Stroke patients with unknown onset (UKO) are excluded from thrombolytic therapy. We aim to study the safety and efficacy of intravenous alteplase in ischemic stroke patients with UKO of symptoms compared with those treated within 4.5... more
Stroke patients with unknown onset (UKO) are excluded from thrombolytic therapy. We aim to study the safety and efficacy of intravenous alteplase in ischemic stroke patients with UKO of symptoms compared with those treated within 4.5 hours in a large cohort. Data were analyzed from 47 237 patients with acute ischemic stroke receiving intravenous tissue-type plasminogen activator in hospitals participating in the Safe Implementation of Treatment in Stroke-International Stroke Thrombolysis Registry between 2010 and 2014. Two groups were defined: (1) patients with UKO (n=502) and (2) patients treated within 4.5 hours of stroke onset (n=44 875). Outcome measures were symptomatic intracerebral hemorrhage per Safe Implementation of Treatment in Stroke on the 22 to 36 hours post-treatment neuroimaging and mortality and functional outcome assessed by the modified Rankin Scale at 3 months. Patients in UKO group were significantly older, had more severe stroke at baseline, and longer door-to-...
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Research Interests: Research Design, Magnetic Resonance Imaging, Treatment Outcome, Czech Republic, Humans, and 15 moreFemale, Male, Risk factors, Clinical Sciences, Aged, Middle Aged, Adult, Time Factors, Risk Factors, Clinical Protocols, Fibrinolysis, Predictive value of tests, Cerebral Infarction, Carotid Stenosis, and Cardiovascular medicine and haematology
Interferon-β (IFNß) is the first-line treatment for relapsing-remitting multiple sclerosis. Myxovirus resistance protein A (MxA) is a marker of IFNß bioactivity, which may be reduced by neutralizing antibodies (NAbs) against IFNß. The aim... more
Interferon-β (IFNß) is the first-line treatment for relapsing-remitting multiple sclerosis. Myxovirus resistance protein A (MxA) is a marker of IFNß bioactivity, which may be reduced by neutralizing antibodies (NAbs) against IFNß. The aim of the study was to analyze the kinetics of MxA mRNA expression during long-term IFNβ treatment and assess its predictive value. A prospective, observational, open-label, non-randomized study was designed in multiple sclerosis patients starting IFNß treatment. MxA mRNA was assessed prior to initiation of IFNß therapy and every three months subsequently. NAbs were assessed every six months. Assessment of relapses was scheduled every three months during 24 months of follow up. The disease activity was correlated to the pretreatment baseline MxA mRNA value. In NAb negative patients, clinical status was correlated to MxA mRNA values. 119 patients were consecutively enrolled and 107 were included in the final analysis. There was no correlation of MxA mR...
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Variable response after clopidogrel is well documented and may affect major adverse clinical events after stroke. Impact of CYP2C19 genetic polymorphisms is an established marker linked to variable response after clopidogrel. However, the... more
Variable response after clopidogrel is well documented and may affect major adverse clinical events after stroke. Impact of CYP2C19 genetic polymorphisms is an established marker linked to variable response after clopidogrel. However, the association of certain genetic polymorphisms with prediction of major adverse clinical events following stroke still remains controversial, especially in Caucasians. The primary aim was to evaluate the impact of CYP2C19 allele *2 in heterozygote form on major adverse clinical events in Caucasian poststroke survivors treated with clopidogrel. The secondary aim was to analyze the potential link between CYP2C19 genetic polymorphism and variable response after clopidogrel. One hundred thirty patients of Caucasian origin following documented ischemic stroke were included. Platelet reactivity was assessed by light transmittance aggregometry (LTA) and matched with various CYP2C19 loss-of-function genetic polymorphisms and major adverse clinical events (composite of vascular deaths, stroke/transient ischemic attack, and myocardial infarction). Over the mean follow-up of 14.9 months, 19 patients experienced major adverse clinical events. The risk of major adverse clinical events was nearly 3-fold in loss-of-function allele carriers (hazard ratio = 2.904; 95% confidence interval, 1.083-7.786; P = 0.013), whereas the risk of ischemic stroke or transient ischemic attack alone was also higher (hazard ratio = 3.170; 95% confidence interval, 1.281-7.849; P = 0.034). Platelet activity was strongly associated with allele *2 status (rs = 0.21, P = 0.016) but not with other genetic polymorphisms. Carriers of allele*2 exhibited lower platelet response to adenosine diphosphate-mean LTA (30.1% vs. 42.0%; P = 0.017). There were no significant differences in LTA results with other agonists. Strong association of increase in adenosine diphosphate-induced aggregation with diabetes mellitus (rs = 0.20, P = 0.023), increasing age (rs = 0.23, P = 0.008), and conversely diminishing over increased weight (rs = 0.23, P = 0.009) was also detected. The carriers of other gene allele variants lack uniformed impact on variable response after clopidogrel. Even heterozygous CYP2C19*2 allele carriers among Caucasian patients after ischemic stroke had a higher risk of major adverse clinical events. The LTA, however, did not predict major adverse clinical events. The exact clinical utility of these findings is still uncertain and requires large outcome-driven randomized trial in Caucasians for proof of concept.
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PEGASUS trial reported reduction of composite primary endpoint after conventional 180mg/daily ticagrelor (CT), and lower 120mg/daily dose ticagrelor (LT) at expense of extra bleeding. Following approval of CT and LT for long-term... more
PEGASUS trial reported reduction of composite primary endpoint after conventional 180mg/daily ticagrelor (CT), and lower 120mg/daily dose ticagrelor (LT) at expense of extra bleeding. Following approval of CT and LT for long-term secondary prevention indication, recent FDA review verified some bleeding outcomes in PEGASUS. To compare the risks after CT and LT against placebo by seven TIMI scale variables, and 9 bleeding categories considered as serious adverse events (SAE) in light of PEGASUS drug discontinuation rates (DDR). The DDR in all PEGASUS arms was high reaching astronomical 32% for CT. The distribution of some outcomes (TIMI major, trauma, epistaxis, iron deficiency, hemoptysis, and anemia) was reasonable. However, the TIMI minor events were heavily underreported when compared to similar trials. Other bleedings (intracranial, spontaneous, hematuria, and gastrointestinal) appear sporadic, lacking expected dose-dependent impact of CT and LT. Few SAE outcomes (fatal, ecchymos...
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Long-awaiting PHILO trial, conducted in 2011-2012 has been submitted and published late in 2015. In contrast to overall PLATO results, but similar to PLATO-US cohort, PHILO revealed numerical inferiority of ticagrelor with regard to... more
Long-awaiting PHILO trial, conducted in 2011-2012 has been submitted and published late in 2015. In contrast to overall PLATO results, but similar to PLATO-US cohort, PHILO revealed numerical inferiority of ticagrelor with regard to death, myocardial infarction, stroke, and bleeding over clopidogrel. Hence, we comprehend the PHILO results in light of the PLATO-US evidence. To assess the PHILO (n=801) outcomes, applied statistics, and trial conduct, matching them with the PLATO-US (n=1413) patients. The Asian, predominantly Japanese ticagrelor patients had worsened outcomes even when compared to the negative American cohort with regard to death (OR=1.44 (PHILO) vs. 1.17 (PLATO-US); myocardial infarction (OR=1.63 vs. 1.38); and composite primary endpoint (OR=1.60 vs. 1.27); but not for stroke (OR=1.51 vs. 1.75). Moreover, in contrast to the trend in PLATO-US (OR=1.11; CI=0.84-1.48, p=0.46), PHILO revealed significant excess of PLATO-defined composite of major and minor bleeding events...
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Warfarin is a cornerstone of oral anticoagulation for stroke prevention. Anticoagulation with warfarin in patients with atrial fibrillation is over twice as effective in secondary prevention of stroke as any other tested alternatives,... more
Warfarin is a cornerstone of oral anticoagulation for stroke prevention. Anticoagulation with warfarin in patients with atrial fibrillation is over twice as effective in secondary prevention of stroke as any other tested alternatives, including all other antithrombotic drugs or surgical interventions. General belief is that warfarin is capable of preventing 20 ischemic strokes for every hemorrhagic one it causes. However, warfarin is one of the most feared agents as a result of its woeful safety profile and difficulties in maintaining the proper daily dose. Recent research in pharmacogenetics predominantly focused on elucidating the influence of individual genetic predispositions to administered warfarin. Although the incorporation of genotype information improves the accuracy of adequate dose prediction, an improvement in anticoagulation control or a reduction in hemorrhagic complications has not been yet convincingly demonstrated. It is clear that identifying an individual patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s risk for hemorrhage on warfarin will require more broad clinical and genetic studies. Future research focused on patients with stroke should concentrate on defining the possible differences, especially focusing on predicting bleeding events in general and intracranial hemorrhages in particular. The purpose of this review is to summarize the existing evidence about pharmacogenetics of warfarin in general, especially focusing on stroke prevention.
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TCD s podáním pulmolabilní echokontrastní látky umožňuje s vysokou senzitivitou detekovat pravo-levý srdeční zkrat, kterým je nejčastěji PFO. TCD umožňuje kvantifikovat míru, a tedy i riziko zkratu a dále odhadnout jeho lokalizaci... more
TCD s podáním pulmolabilní echokontrastní látky umožňuje s vysokou senzitivitou detekovat pravo-levý srdeční zkrat, kterým je nejčastěji PFO. TCD umožňuje kvantifikovat míru, a tedy i riziko zkratu a dále odhadnout jeho lokalizaci (extra-nebo intrakardiální). Oproti ...
... 2. Hesse D, Sellebjerg F, Soelberg Sorensen P. Absence of MxA induction by interferon ² in patients with MS reflects comple-te loss ... medzi finalistov v štyroch kategóriách – ďalšími dvomi kategóriami, v ktorých bola nominovaná,... more
... 2. Hesse D, Sellebjerg F, Soelberg Sorensen P. Absence of MxA induction by interferon ² in patients with MS reflects comple-te loss ... medzi finalistov v štyroch kategóriách – ďalšími dvomi kategóriami, v ktorých bola nominovaná, boli „Executive of the Year – Glenn Saldanha“ a ...
The optimal utilization of antiplatelet therapy in patients with renal impairment (RI) following acute coronary syndromes (ACS) represents an urgent, unmet and yet unsolved need with regards to the choice of agents, duration of treatment... more
The optimal utilization of antiplatelet therapy in patients with renal impairment (RI) following acute coronary syndromes (ACS) represents an urgent, unmet and yet unsolved need with regards to the choice of agents, duration of treatment and potential dose/regimen adjustment. The lack of any large randomized trials designed and powered specifically in such high-risk patients, absence of the uniformed efficacy and safety data reporting policy to the FDA and endless overoptimistic publications based on post hoc analyses of primary trials sometimes exaggerating benefits and hiding risks, clouds reality. In addition, triaging RI patients is problematic due to ongoing kidney deterioration and the fact that such patients are prone to both vascular occlusions and bleeding. The authors summarize available FDA-confirmed evidence from the latest trials with approved antiplatelet agents, namely clopidogrel (CAPRIE, CURE, CREDO, CLARITY, CHARISMA); prasugrel (TRITON, TRILOGY); ticagrelor (PLATO, and PEGASUS); and vorapaxar (TRACER and TRA2P) in RI patient cohorts on top of aspirin as part of dual antiplatelet therapy (DAPT). We deliberately avoided any results unless they were verified by the FDA, with the exception of the recent PEGASUS, since Agency reviews are not yet available. Despite differences among the trials and DAPT choices, RI patients universally experience much higher (HR = 1.3-3.1) rates of primary endpoint events, and bleeding risks (HR = 1.7-3.6). However, only ticagrelor increases creatinine and uric acid levels above that of clopidogrel; has the worst incidence of serious adverse events, more adverse events, and inferior outcomes in patients with severe (eGFR &amp;amp;amp;amp;amp;amp;lt;30 ml/min), especially in the lowest (eGFR &amp;amp;amp;amp;amp;amp;lt;15 ml/min) RI subsets. Clopidogrel, prasugrel and vorapaxar appear safer. Moreover, less aggressive half dose (5 mg/daily) prasugrel and strict DAPT, are well justified in RI, but not predominantly triple strategies with vorapaxar as tested in TRA2P and especially in TRACER. In conclusion, data from clinical trials, their sub-studies and affiliated FDA reviews indicate that RI cause more vascular occlusions and bleeding in ACS patients treated with DAPT. Among the novel antiplatelet agents, prasugrel and vorapaxar, but probably not ticagrelor, offer advantage in RI patients.
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Even with its narrow therapeutic index, interindividual variability in daily dose and possible serious bleeding complications, is warfarin the mainstay of therapy and prevention of thromboembolic disease. The application of... more
Even with its narrow therapeutic index, interindividual variability in daily dose and possible serious bleeding complications, is warfarin the mainstay of therapy and prevention of thromboembolic disease. The application of pharmacogenetics in testing individual polymorphisms of two genes CYP 2C9 (pharmacokinetics of warfarin) and VKORC1 (sensitivity on warfarin) is promising tactics leading to a safe anticoagulation. The first of two applications of pharmacogenetics is assesment of the daily dose of warfarin for individual patients even before starting the therapy. The second is the risk stratification of already warfarinized patients: The carriers of variant genotype are in a greater risk of bleeding complications. The following article is dedicated to the evaluation of literature and our own laboratory and clinical experience with these applications in clinical practise.