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1.
J Am Heart Assoc ; 10(1): e018184, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33327737

RESUMO

Background Type 2 diabetes mellitus is a risk factor for lower extremity arterial disease. Cilostazol expresses antiplatelet, anti-inflammatory, and vasodilator actions and improves the claudication intermittent symptoms. We investigated the efficacy and safety of adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus exhibiting symptomatic lower extremity arterial disease, in the prevention of ischemic vascular events and improvement of the claudication intermittent symptoms. Methods and Results In a prospective 2-arm, multicenter, open-label, phase 4 trial, patients with type 2 diabetes mellitus with intermittent claudication receiving clopidogrel (75 mg/d) for at least 6 months, were randomly assigned in a 1:1 ratio, either to continue to clopidogrel monotherapy, without receiving placebo cilostazol (391 patients), or to additionally receive cilostazol, 100 mg twice/day (403 patients). The median duration of follow-up was 27 months. The primary efficacy end point, the composite of acute ischemic stroke/transient ischemic attack, acute myocardial infarction, and death from vascular causes, was significantly reduced in patients receiving adjunctive cilostazol compared with the clopidogrel monotherapy group (sex-adjusted hazard ratio [HR], 0.468; 95% CI, 0.252-0.870; P=0.016). Adjunctive cilostazol also significantly reduced the stroke/transient ischemic attack events (sex-adjusted HR, 0.38; 95% CI, 0.15-0.98; P=0.046) and improved the ankle-brachial index and pain-free walking distance values (P=0.001 for both comparisons). No significant difference in the bleeding events, as defined by Bleeding Academic Research Consortium criteria, was found between the 2 groups (sex-adjusted HR, 1.080; 95% CI, 0.579-2.015; P=0.809). Conclusions Adjunctive cilostazol to clopidogrel-treated patients with type 2 diabetes mellitus with symptomatic lower extremity arterial disease may lower the risk of ischemic events and improve intermittent claudication symptoms, without increasing the bleeding risk, compared with clopidogrel monotherapy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02983214.


Assuntos
Isquemia Encefálica , Cilostazol , Clopidogrel , Diabetes Mellitus Tipo 2/complicações , Claudicação Intermitente , Infarto do Miocárdio , Idoso , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologia , Isquemia Encefálica/mortalidade , Isquemia Encefálica/prevenção & controle , Cilostazol/administração & dosagem , Cilostazol/efeitos adversos , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada/métodos , Feminino , Humanos , Claudicação Intermitente/complicações , Claudicação Intermitente/terapia , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/fisiopatologia , Masculino , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Avaliação de Processos e Resultados em Cuidados de Saúde , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Resultado do Tratamento
2.
J Cardiol Cases ; 22(6): 273-275, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33304419

RESUMO

The development of angina in the setting of new-onset left bundle branch block (LBBB) that resolves at the same time with the disappearance of LBBB, without coexistent myocardial ischemia, denotes the painful LBBB syndrome. In this illustrative case report we describe a young male patient with painful LBBB syndrome. The LBBB was rate-dependent occurring during exercise and the patient was successfully treated with bisoprolol. We also provide a concise review of the literature and we briefly discuss the diagnosis and management of this clinical entity. .

3.
Hellenic J Cardiol ; 61(6): 362-377, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33045394

RESUMO

The perception that women represent a low-risk population for cardiovascular (CV) disease (CVD) needs to be reconsidered. Starting from risk factors, women are more likely to be susceptible to unhealthy behaviors and risk factors that have different impact on CV morbidity and mortality as compared to men. Despite the large body of evidence as regards the effect of lifestyle factors on the CVD onset, the gender-specific effect of traditional and non-traditional risk factors on the prognosis of patients with already established CVD has not been well investigated and understood. Furthermore, CVD in women is often misdiagnosed, underestimated, and undertreated. Women also experience hormonal changes from adolescence till elder life that affect CV physiology. Unfortunately, in most of the clinical trials women are underrepresented, leading to the limited knowledge of CV and systemic impact effects of several treatment modalities on women's health. Thus, in this consensus, a group of female cardiologists from the Hellenic Society of Cardiology presents the special features of CVD in women: the different needs in primary and secondary prevention, as well as therapeutic strategies that may be implemented in daily clinical practice to eliminate underestimation and undertreatment of CVD in the female population.


Assuntos
Cardiologia , Doenças Cardiovasculares , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Feminino , Humanos , Masculino , Fatores de Risco , Prevenção Secundária , Saúde da Mulher
4.
Arch Med Sci ; 16(5): 1013-1021, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32863989

RESUMO

INTRODUCTION: The use of generic drugs is continuously growing; however, there are limited epidemiological data regarding the therapeutic equivalence of each original drug formulation with its generic counterparts. We evaluated the 12-month composite endpoint of recurrent acute myocardial infarction, ischaemic stroke, cardiac deaths, or hospitalisation due to a major bleeding in acute coronary syndrome (ACS) patients treated with original clopidogrel or a generic clopidogrel formulation, in relation to sociodemographic and clinical characteristics. MATERIAL AND METHODS: Consecutive Greek ACS patients (n = 1194) hospitalised in the Aegean islands and the Attica region were enrolled. Clopidogrel treatment was recorded either as original clopidogrel hydrogen sulphate (Plavix®/Iscover®) or as a generic clopidogrel besylate formulation (Clovelen®). The composite endpoint was recorded at 12-month follow-up. RESULTS: The 12-month composite endpoint was 3.9% (4.6% in the Aegean islands and 3.5% in the Attica area, p > 0.05). The respective incidence in men was 4.0% and in women 3.8% (p > 0.05). Overall, generic and original clopidogrel use was 87% and 13% of patients, respectively. No significant differences were observed between original and generic clopidogrel use and 12-month composite endpoint incidence. Subgroup analysis with gender, region of residence, and clinical and lifestyle factors as strata did not reveal any significant outcomes. Haemorrhage incidence did not exceed 1% in the total sample. CONCLUSIONS: The use of a generic clopidogrel besylate formulation was quite high in both urban and insular areas of Greece and had similar efficacy and safety profile with the original clopidogrel salt, supporting the routine use of this low-cost generic clopidogrel in the management of cardiovascular disease patients.

5.
Curr Vasc Pharmacol ; 17(6): 635-643, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29866011

RESUMO

BACKGROUND: Triflusal has demonstrated an efficacy similar to aspirin in the prevention of vascular events in patients with acute myocardial infarction (ΜΙ) and ischaemic stroke but with less bleeding events. OBJECTIVE: We performed a randomised, multicentre, phase 4 clinical trial to compare the clinical efficacy and safety of triflusal versus aspirin, administered for 12 months in patients eligible to receive a cyclooxygenase-1 (COX-1) inhibitor. METHODS: Patients with stable coronary artery disease or with a history of non-cardioembolic ischaemic stroke were randomly assigned to receive either triflusal 300 mg twice or 600 mg once daily or aspirin 100 mg once daily for 12 months. The primary efficacy endpoint was the composite of: (a) ΜΙ, (b) stroke (ischaemic or haemorrhagic), or, (c) death from vascular causes for the entire follow-up period. The primary safety endpoints were the rate of bleeding events as defined by Bleeding Academic Research Consortium (BARC) criteria. RESULTS: At 12-month follow-up, an equivalent result was revealed between the triflusal (n=559) and aspirin (n=560) in primary efficacy endpoint. Specifically, the combined efficacy outcome rate (i.e. MI, stroke or death from vascular causes) difference was equal to -1.3% (95% confidence interval -1.1 to 3.5) and lied within the a-priori defined equivalence interval (p<0.001). Regarding the primary safety endpoints, patients on triflusal treatment were 50% less likely to develop bleeding events according to the BARC criteria, and especially any clinically overt sign of haemorrhage that requires diagnostic studies, hospitalisation or special treatment (BARC type 2). CONCLUSION: The efficacy of triflusal in the secondary prevention of vascular events is similar to aspirin when administered for 12 months. Importantly, triflusal significantly reduced the incidence of ΜΙ and showed a better safety profile compared with aspirin. (ASpirin versus Triflusal for Event Reduction In Atherothrombosis Secondary prevention, ASTERIAS trial; Clinical Trials.gov Identifier: NCT02616497).


Assuntos
Aspirina/uso terapêutico , Isquemia Encefálica/prevenção & controle , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Embolia Intracraniana/prevenção & controle , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Salicilatos/uso terapêutico , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controle , Idoso , Aspirina/efeitos adversos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/mortalidade , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Inibidores de Ciclo-Oxigenase/efeitos adversos , Feminino , Grécia , Hemorragia/induzido quimicamente , Humanos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/mortalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Inibidores da Agregação Plaquetária/efeitos adversos , Recidiva , Fatores de Risco , Salicilatos/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo , Resultado do Tratamento
6.
Drugs Aging ; 34(12): 917-923, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29177885

RESUMO

OBJECTIVES: The objective of this study was to test platelet function pre- and peri-operatively in clopidogrel-treated patients undergoing transurethral resection of the prostate. METHODS: This was a pilot study involving 20 male patients treated with clopidogrel (75 mg/day) for the secondary prevention of cardiovascular disease and scheduled for elective transurethral resection of the prostate. Platelet function testing with light transmittance aggregometry in platelet-rich plasma of four samples (T0, T1, T2, and T3 drawn on the same day, 3 and 7 days of clopidogrel cessation and 24-h post-operatively, respectively) was performed and evaluated in each patient. P-selectin membrane expression was evaluated using monoclonal antibodies. RESULTS: The platelet response to adenosine diphosphate 5 µΜ and 20 µΜ at T0 were 42 ± 15 and 60 ± 14%, respectively. After discontinuation of clopidogrel, corresponding maximum aggregation values at T1 were 60 ± 16 and 74 ± 14%, and increased to 69 ± 16 and 79 ± 18% at T2. No significant difference in platelet aggregation values were noted between T1 and T2, while similar aggregation values were recorded at T3. CONCLUSIONS: Our findings indicate that in patients undergoing transurethral resection of the prostate, platelet activation is similar 3 and 7 days from clopidogrel cessation. These results may be of relevance in subjects at increased thrombotic risk prior to a surgical procedure carrying a high-bleeding risk.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Hiperplasia Prostática/cirurgia , Ticlopidina/análogos & derivados , Ressecção Transuretral da Próstata/métodos , Idoso , Doenças Cardiovasculares/sangue , Clopidogrel , Humanos , Masculino , Selectina-P/biossíntese , Projetos Piloto , Agregação Plaquetária , Inibidores da Agregação Plaquetária/administração & dosagem , Testes de Função Plaquetária , Medicina de Precisão/métodos , Hiperplasia Prostática/sangue , Ticlopidina/administração & dosagem
7.
J Cardiovasc Pharmacol Ther ; 21(6): 516-525, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27081185

RESUMO

BACKGROUND: In the present clinical trial, we compared the efficacy and safety of the generic clopidogrel besylate (CB) with the innovator clopidogrel hydrogen sulfate (CHS) salt in patients eligible to receive clopidogrel. METHODS: A prospective 2-arm, multicenter, open-label, phase 4 clinical trial. Consecutive patients (n = 1864) were screened and 1800 were enrolled in the trial and randomized to CHS or CB. Primary efficacy end point was the composite of myocardial infarction, stroke, or death from vascular causes, and primary safety end point was rate of bleeding events as defined by Bleeding Academic Research Consortium criteria. RESULTS: At 12-month follow-up, no differences were observed between CB (n = 759) and CHS (n = 798) in primary efficacy and safety end points (age, sex, history of percutaneous coronary intervention adjusted odds ratio [OR], 0.70; 95% confidence interval [CI], 0.41-1.21 and OR, 0.81; 95% CI, 0.51-1.29, respectively) between CHS and CB. Analyses of efficacy and safety in subgroups that were defined according to the qualifying diagnosis revealed that there was no difference between CHS and CB. CONCLUSION: The efficacy and safety of CB administered for 12 months for the secondary prevention of atherothrombotic events are similar to that of CHS. (Salts of Clopidogrel: Investigation to ENsure Clinical Equivalence, SCIENCE trial; ClinicalTrials.gov Identifier:NCT02126982).


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Medicamentos Genéricos/uso terapêutico , Inibidores da Agregação Plaquetária/uso terapêutico , Prevenção Secundária/métodos , Ticlopidina/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/mortalidade , Clopidogrel , Composição de Medicamentos , Medicamentos Genéricos/efeitos adversos , Medicamentos Genéricos/química , Feminino , Grécia , Hemorragia/induzido quimicamente , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Razão de Chances , Intervenção Coronária Percutânea , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/química , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Equivalência Terapêutica , Ticlopidina/efeitos adversos , Ticlopidina/química , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
8.
Glob Heart ; 10(4): 255-63, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26260581

RESUMO

BACKGROUND: Low socioeconomic status is associated with poorer cardiovascular health. OBJECTIVES: The aim of the present work was to evaluate how social and economic factors influence modifiable cardiovascular disease risk factors and thus, acute coronary syndrome or ischemic stroke presence. METHODS: One thousand participants were enrolled; 250 consecutive patients with a first acute coronary syndrome (83% were male, 60 ± 12 years old) and 250 control subjects, as well as 250 consecutive patients with a first ischemic stroke (56% were male, 77 ± 9 years old) and 250 control subjects. The control subjects were population-based and age-sex matched with the patients. Detailed information regarding their medical records, lifestyle characteristics, education level, financial status satisfaction, and type of occupation were recorded. RESULTS: After controlling for potential confounding factors, significant inverse associations were observed regarding financial status satisfaction and sedentary/mental type occupation with acute coronary syndrome or stroke presence, but not with the educational level. Nevertheless, further evaluation using path analysis, revealed quite different results, indicating that the education level influenced the type of occupation and financial satisfaction, hence affecting indirectly the likelihood of developing a cardiovascular disease event. CONCLUSIONS: Social and economic parameters interact with modifiable cardiovascular disease risk factors through multiple pathways.


Assuntos
Síndrome Coronariana Aguda/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Distribuição por Idade , Idoso , Estudos de Casos e Controles , Feminino , Grécia/epidemiologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Fatores Socioeconômicos
9.
Angiology ; 65(6): 473-90, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23966569

RESUMO

Ischemic heart disease and cerebrovascular disease remain major health problems with associated mortality and quality-of-life consequences. Antiplatelet agents, including thienopyridines and the new P2Y12 inhibitors, have been shown to improve survival in the secondary prevention setting. We review the available evidence on the effectiveness and safety of previous established as well as novel antithrombotic agents in the secondary prevention of cardiovascular disease with a special focus on cerebrovascular disease.


Assuntos
Ataque Isquêmico Transitório/prevenção & controle , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação Plaquetária/uso terapêutico , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controle , Quimioterapia Combinada , Inibidores do Fator Xa/uso terapêutico , Fibrinolíticos/uso terapêutico , Humanos
10.
Curr Vasc Pharmacol ; 12(5): 766-77, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23885646

RESUMO

Clopidogrel is a thienopyridine that selectively and irreversibly inhibits the ADP purinergic receptor P2Y12 and the subsequent ADP-mediated platelet activation. Clopidogrel has been approved for clinical use as clopidogrel hydrogen sulfate (bisulfate) salt. The clinical usefulness of clopidogrel bisulfate salt has been proved in a wide variety of large scale clinical trials, thus clopidogrel bisulfate has been extensively used in a large spectrum of patients been under thrombotic risk. Recently, several generic clopidogrel formulations have been approved for clinical use. Consequently, clopidogrel is currently a cost-effective antiplatelet agent. Only small studies have compared the pharmacokinetic and pharmacodynamic properties of various clopidogrel generic salt formulations with the innovator bisulfate salt. In addition few data are available concerning the clinical efficacy and safety of these generic clopidogrel formulations in order to guide clinicians in deciding when generic substitution is appropriate. The aim of this review is to summarize the physicochemical properties as well as the pharmacokinetic and pharmacodynamic characteristics of the generic clopidogrel salts. We also critically present existing data on the clinical efficacy and safety of the generic clopidogrel formulations compared with the innovator clopidogrel bisulfate salt in patients with cardiovascular disease.


Assuntos
Inibidores da Agregação Plaquetária/química , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/análogos & derivados , Animais , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/metabolismo , Química Farmacêutica , Ensaios Clínicos como Assunto/métodos , Clopidogrel , Medicamentos Genéricos/química , Medicamentos Genéricos/farmacocinética , Medicamentos Genéricos/uso terapêutico , Humanos , Inibidores da Agregação Plaquetária/farmacocinética , Ticlopidina/química , Ticlopidina/farmacocinética , Ticlopidina/uso terapêutico
12.
Artif Intell Med ; 59(3): 175-83, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24080079

RESUMO

OBJECTIVE: To compare the accuracy of a-priori and a-posteriori dietary patterns in the prediction of acute coronary syndrome (ACS) and ischemic stroke. This is actually the first study to employ state-of-the-art classification methods for this purpose. METHODS AND MATERIALS: During 2009-2010, 1000 participants were enrolled; 250 consecutive patients with a first ACS and 250 controls (60±12 years, 83% males), as well as 250 consecutive patients with a first stroke and 250 controls (75±9 years, 56% males). The controls were population-based and age-sex matched to the patients. The a-priori dietary patterns were derived from the validated MedDietScore, whereas the a-posteriori ones were extracted from principal components analysis. Both approaches were modeled using six classification algorithms: multiple logistic regression (MLR), naïve Bayes, decision trees, repeated incremental pruning to produce error reduction (RIPPER), artificial neural networks and support vector machines. The classification accuracy of the resulting models was evaluated using the C-statistic. RESULTS: For the ACS prediction, the C-statistic varied from 0.587 (RIPPER) to 0.807 (MLR) for the a-priori analysis, while for the a-posteriori one, it fluctuated between 0.583 (RIPPER) and 0.827 (MLR). For the stroke prediction, the C-statistic varied from 0.637 (RIPPER) to 0.767 (MLR) for the a-priori analysis, and from 0.617 (decision tree) to 0.780 (MLR) for the a-posteriori. CONCLUSION: Both dietary pattern approaches achieved equivalent classification accuracy over most classification algorithms. The choice, therefore, depends on the application at hand.


Assuntos
Algoritmos , Dieta , Síndrome Coronariana Aguda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Acidente Vascular Cerebral/diagnóstico
13.
World J Cardiol ; 5(7): 242-6, 2013 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-23888193

RESUMO

AIM: To examine the effect of ibutilide on novel indexes of repolarization in patients with persistent atrial fibrillation (AF). METHODS: We studied consecutive patients scheduled for elective electrical cardioversion. Intravenous ibutilide (1 + 1 mg) was administered before the electrical cardioversion while close electrocardiographic (ECG) monitoring was performed. ECG indexes such as corrected QT interval (QTc), the interval from the peak until the end of T wave (Tpe), and the Tpe/QT ratio were measured before ibutilide infusion and 10 min after the end of infusion. RESULTS: The final study population consisted of 20 patients (mean age: 67.1 ± 9.9 years, 10 men). Six patients were cardioverted pharmacologically and did not proceed to electrical cardioversion. Two patients developed short non-sustained episodes of torsades de pointes ventricular tachycardia. All but one of the aforementioned ECG indexes increased significantly after ibutilide administration. In specific, the QTc interval increased from 442 ± 29 to 471 ± 37 ms (P = 0.037), the Tpe interval in precordial leads from 96 ms (range 80-108 ms) to 101 ms (range 91-119 ms) (P = 0.021), the Tpe interval in lead II from 79 ms (range 70-88 ms) to 100 ms (range 87-104 ms) (P < 0.001), the Tpe/QT ratio in precordial leads from 0.23 ms (range 0.18-0.26 ms) to 0.26 ms (range 0.23-0.28 ms) (P = 0.028), and the Tpe interval dispersion from 25 ms (range 23-30 ms) to 35 ms (range 27-39 ms) (P = 0.012). However, the Tpe/QT ratio in lead II did not change significantly. CONCLUSION: Ibutilide increases the duration and dispersion of ventricular repolarization. The prognostic value of Tpe and Tpe/QT in the setting of drug-induced proarrhythmia needs further study.

14.
Pacing Clin Electrophysiol ; 36(3): 322-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23305256

RESUMO

BACKGROUND: Sudden cardiac death is prevalent in chronic hemodialysis (HD) patients while the dialysis process may have arrhythmogenic potential. We sought to examine the effect of HD on conventional electrocardiographic parameters as well as on novel indexes of repolarization, given that increased spatial dispersion of repolarization is related to ventricular arrhythmias. METHODS: We recorded clinical, echocardiographic, and laboratory parameters as well as electrocardiographic indexes before and after a single HD session. Specifically, we calculated the QTc interval, the QRS duration, the T peak-to-end (Tpe) interval, and the Tpe/QT ratio. RESULTS: The study population consisted of 66 chronic HD patients (mean age: 68.9 ± 11.8 years, 40 males). Heart rate, blood pressure, QRS duration, QTc interval, and QT dispersion did not change significantly after the HD session. However, the Tpe interval and the Tpe/QT ratio increased significantly (80 [65-90] ms vs 85 [77.5-100] ms; P = 0.04, and 0.21 [0.18-0.24] vs 0.25 [0.21-0.28]; P = 0.05, respectively). Correlation analysis and multiple regression analysis failed to show significant associations between the baseline parameters and the baseline values of Tpe and Tpe/QT or between the change of the laboratory parameters during HD and the corresponding change of the Tpe and the Tpe/QT values. No significant arrhythmias were observed during the HD sessions. CONCLUSIONS: HD induces an increase in novel markers of spatial dispersion of ventricular repolarization. Whether the assessment of these indexes of heterogeneity of repolarization at baseline or their change during HD has a prognostic value with regard to future untoward events, remains to be elucidated.


Assuntos
Eletrocardiografia , Ventrículos do Coração/fisiopatologia , Falência Renal Crônica/fisiopatologia , Diálise Renal , Idoso , Feminino , Humanos , Falência Renal Crônica/complicações , Masculino , Projetos Piloto
15.
Atherosclerosis ; 225(1): 187-93, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22975231

RESUMO

OBJECTIVES: The aim of the present work was to evaluate the association between salt and salty food consumption on the development of an acute coronary syndrome (ACS) or ischemic stroke, under the context of adherence to the Mediterranean diet. METHODS: During 2009-2010, 1000 participants were enrolled; 250 were consecutive patients with a first ACS, 250 were consecutive patients with a first ischemic stroke and 500 population-based, control subjects, one-for-one matched to the patients by age and sex. Socio-demographic, clinical, psychological, dietary and other lifestyle characteristics were measured. Consumption of foods with high salt concentration was evaluated with a special score (range 0-10). Adherence to the Mediterranean diet was assessed by the validated MedDietScore (theoretical range: 0-55). RESULTS: After adjustment for potential confounding factors, use of salt added in table was associated with 81% higher likelihood of stroke (95% Confidence Interval: 1.03-3.20), whereas no association was observed regarding the development of ACS. Salt use during cooking was not associated with the development of ACS or stroke. Each unit increase of the score evaluating total salty food consumption was associated with 33% higher likelihood of stroke development (95% Confidence Interval: 1.08-1.64), but not with ACS. The effect of salt and salty food consumption regarding stroke presence was more evident for participants with lower adherence to the Mediterranean diet. CONCLUSION: Simple dietary changes, with emphasis on reducing salt and salty food consumption, along with better adherence to the Mediterranean diet, should be incorporated in public health strategies for the primary prevention of stroke.


Assuntos
Síndrome Coronariana Aguda/prevenção & controle , Dieta Mediterrânea , Cloreto de Sódio na Dieta/efeitos adversos , Acidente Vascular Cerebral/prevenção & controle , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Retrospectivos
16.
Expert Rev Clin Pharmacol ; 5(3): 319-36, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22697594

RESUMO

Platelets play an important role in atherothrombotic disease. The currently available antiplatelet drugs target key steps of platelet activation including thromboxane A(2) synthesis, ADP-mediated signaling, and glycoprotein IIb/IIIa-mediated platelet aggregation. The improvement of our understanding on the pharmacokinetic and pharmacodynamic characteristics of these drugs enables the tailoring of the most appropriate anti-thrombotic therapy to the individual patient and risk situation in the daily clinical practice. However, current antiplatelet therapies are associated with increased bleeding risk. Thus, further research on platelet functions may give rise to numerous new antiplatelet agents with high anti-thrombotic efficiency and low adverse hemorrhagic side effects.


Assuntos
Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/efeitos dos fármacos , Trombose/prevenção & controle , Tromboxano A2/antagonistas & inibidores , Plaquetas/efeitos dos fármacos , Ensaios Clínicos como Assunto , Humanos , Inibidores da Agregação Plaquetária/farmacocinética , Trombose/metabolismo
17.
Hellenic J Cardiol ; 53(2): 95-100, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22484774

RESUMO

INTRODUCTION: Data regarding sources of oxidative stress in the failing myocardium are sparse. Leukocytes actively participate in the oxidative damage observed in human heart failure (HF). The intracellular labile iron pool (LIP) represents a source of toxic reactive oxygen species. METHODS: We studied patients with chronic systolic HF who had a left ventricular ejection fraction (LVEF) 45%. We examined the LIP status in different populations of leukocytes in HF patients and we investigated its association with clinical and laboratory parameters, including conventional inflammatory markers. RESULTS: Sixty patients were finally included in the analysis (mean age: 67 ± 11 years, 54 men, 42 with ischemic cardiomyopathy). The multivariate logistic regression analysis showed that only LIP in granulocytes (OR: 0.73; 95% CI: 0.55-0.98; p=0.039) and right ventricular systolic pressure (RVSP) (OR: 0.95; 95% CI: 0.92-0.99; p=0.027) were independently associated with severe LV systolic dysfunction (LVEF30%). The correlation analysis revealed that LVEF was inversely associated with LIP in granulocytes (Spearman's rho: -0.39, p=0.002), LIP in monocytes (Spearman's rho: -0.35, p=0.007), and RVSP (Spearman's rho: -0.43, p=0.003). No significant correlation between LVEF and inflammatory indexes was noted. CONCLUSIONS: LIP in granulocytes is independently associated with the severity of LV dysfunction in patients with systolic HF. Intracellular redox active iron may represent a source of leukocyte reactive oxygen species in this setting.


Assuntos
Insuficiência Cardíaca Sistólica/metabolismo , Ferro/metabolismo , Leucócitos/metabolismo , Miocárdio/metabolismo , Função Ventricular Esquerda/fisiologia , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca Sistólica/fisiopatologia , Humanos , Masculino , Estresse Oxidativo , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , Volume Sistólico , Pressão Ventricular
18.
Curr Vasc Pharmacol ; 10(5): 539-49, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22338568

RESUMO

Inflammation of the vascular wall is considered as the principal underlying mechanism in the development of atherosclerosis. Besides their specific functions in haemostasis via thrombus formation after an endothelial injury, a growing body of evidence indicates that platelets play an important role in the inflammatory reactions occurring in the vascular wall as well as in the subsequent tissue repair mechanisms. Platelets interact with activated endothelium as well as with circulating leukocytes and progenitor cells. These interactions, involve direct cell-to-cell interactions as well as autocrine and paracrine pathways, which lead to activation of platelets and their respective cellular counterpart. An increasing body of evidence suggests that antiplatelet therapy may reduce vascular inflammation primarily by inhibiting platelet activation. The aim of the present review is to highlight the molecular basis of platelet-mediated inflammatory response, focusing on the mechanisms underlying the platelet-endothelial cell interaction. The anti-inflammatory effects of current antiplatelet therapies will be also discussed.


Assuntos
Plaquetas/metabolismo , Doenças Cardiovasculares/fisiopatologia , Inflamação/fisiopatologia , Animais , Comunicação Autócrina , Doenças Cardiovasculares/tratamento farmacológico , Endotélio Vascular/patologia , Humanos , Inflamação/tratamento farmacológico , Leucócitos/metabolismo , Comunicação Parácrina , Ativação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Células-Tronco/metabolismo
19.
Expert Opin Pharmacother ; 13(2): 149-58, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22188544

RESUMO

OBJECTIVE: The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. In this study we compared the antiplatelet effectiveness of a generic clopidogrel salt, clopidogrel besylate (CB), with the original CHS in patients with an ACS. RESEARCH DESIGN AND METHODS: Ninety-six ACS patients were randomized to receive a 600-mg loading dose of either CHS (n = 45) or CB (n = 51), followed by 75 mg/day. Sixty-eight patients underwent a percutaneous coronary intervention (PCI), whereas 28 were treated conservatively. Platelet aggregatory response, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression and platelet-leucocyte conjugates were determined before clopidogrel loading (baseline), as well as at 5 days and at 1 month afterwards. RESULTS: No difference in the clopidogrel response variability was observed between patients receiving CHS or CB either at 5 days or at 1 month of follow-up. Similarly, no difference in the inhibition of platelet aggregation, P-selectin expression or in the platelet-leucocyte conjugates was observed between CHS and CB group during the follow-up. CONCLUSIONS: There is no overall significant difference in the antiplatelet efficacy between CB and CHS during their administration in ACS patients for up to 1 month after the episode.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/sangue , Idoso , Clopidogrel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/uso terapêutico
20.
Angiology ; 63(7): 547-51, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22144668

RESUMO

The efficacy of clopidogrel therapy in patients with an acute coronary syndrome (ACS) has been established using the clopidogrel hydrogen sulfate (CHS) formulation. We compared the antiplatelet effectiveness of long-term administration of the original CHS with a generic clopidogrel besylate (CB) salt formulation in 86 patients with a history of an ACS. At 1 month after the episode, patients receiving 75 mg/d CHS were randomized to continue with CHS (n = 41) or to switch to 75 mg/d CB (n = 45). Platelet aggregation, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, P-selectin expression, and platelet-leucocyte conjugates were determined before randomization and at 6 months afterward. No difference in any platelet parameter studied was observed between the 2 groups either before randomization or after 6 months of treatment with CHS or CB. We conclude that there is no difference in the antiplatelet efficacy between CB and CHS during long-term administration in patients with a history of an ACS.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Medicamentos Genéricos/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/sangue , Clopidogrel , Medicamentos Genéricos/efeitos adversos , Humanos , Assistência de Longa Duração , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/efeitos adversos , Ticlopidina/administração & dosagem , Ticlopidina/efeitos adversos , Resultado do Tratamento
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