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4.
Angiol Sosud Khir ; 26(3): 28-36, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33063749

RESUMO

This article presents a review of the literature on studying Cilostazol, a type 3 phosphodiesterase inhibitor, also providing the Russian and foreign statistics on the prevalence of peripheral artery disease. It is underlined that the majority of patients with peripheral artery disease have atherosclerotic lesions in the coronary and cerebral vascular basins. Cilostazol deservedly occupies the first lines in the sections of pharmacotherapy for intermittent claudication in international and Russian consensus documents on peripheral artery disease. The drug has an extensive evidence base for the following pharmacological effects: vasodilating, antiplatelet, endothelial protective, and vasculogenic. Clinical efficacy of Cilostazol was confirmed in 15 randomized clinical trials (3 718 patients with intermittent claudication) studying the use of Cilostazol taken twice daily at doses of 50 mg, 100 mg, and 150 mg as compared with placebo or versus pentoxifylline given in a dose of 400 mg three times daily, with a demonstrable increase in the pain-free walking distance and the maximal walking distance on the background of taking Cilostazol. The drug significantly improves the outcomes of endovascular interventions on arteries of lower extremities, decreasing the incidence of restenosis, prolonging limb survival, and reducing the frequency of major amputations. Many studies addressing the use of Cilostazol in patients with coronary and cerebral atherosclerosis have investigated the effect of the drug as a component of dual antiplatelet therapy (aspirin + Cilostazol) and triple antiplatelet therapy (aspirin + clopidogrel + Cilostazol) after endovascular interventions. The addition of Cilostazol to treatment resulted in a significant decrease in the occurrence of re-stenosis, with no increase in the incidence of haemorrhage. Cilostazol may be recommended for patients with multifocal atherosclerosis and resistance to aspirin and clopidogrel. Also presented in the article are the results of a Russian clinical trial studying comparative efficacy of Cilostazol and pentoxifylline in patients with intermittent claudication.


Assuntos
Cilostazol , Doença Arterial Periférica , Humanos , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/tratamento farmacológico , Federação Russa , Tetrazóis
5.
Orv Hetil ; 161(38): 1637-1645, 2020 09.
Artigo em Húngaro | MEDLINE | ID: mdl-32924968

RESUMO

INTRODUCTION: Intermittent claudication has a significant negative impact on the patients' quality of life. Revascularization procedures and noninvasive medical therapies can improve walking capacity. Cilostazol has IA recommendation for the treatment of intermittent claudication. AIM: The aim of this study was to evaluate the effect of a three-month cilostazol treatment on the health-related quality of life and on the lower-limb functional capacity in diabetic (DM) and non-diabetic patients (NDM) with intermittent claudication in the clinical practice. METHOD: The study was a multicenter, non-interventional trial; 812 patients with peripheral artery disease (Fontaine II stage, mean age: 67.17 years, male/female: 58.25/41.75%, 318 diabetics) were enrolled, who received cilostazol (50 or 100 mg twice a day) for 3 months. The quality of life was evaluated with the EQ-5D-3L questionnaire, the functional capacity with the WELCH questionnaire. Walking distances, ankle-brachial index were measured at baseline and after 3 months. RESULTS: Upon conclusion of the study, the EQ-5D index improved both in non-diabetic and diabetic patients (baseline: NDM -0.45 ± 0.22, DM -0.48 ± 0.23, 3rd month: -0,24 ± 0.18, -0,27 ± 0.19; respectively; p<0.0001) and there was a significant increase in the WELCH score as well (baseline: NDM 20 ± 14, DM 18 ± 14; 3rd month: 33 ± 19, 29 ± 16, respectively; p<0.0001). Both pain-free and maximal walking distance increased by 59.2% (median: 50.0%), 46.58 (median: 40.51%) in NDM and 42.85% (median: 43.33%), 41.61% (median: 34.68%) in DM patients, respectively (p<0.001). CONCLUSIONS: Three months of cilostazol treatment improved the quality of life and lower-limb functional capacity in diabetic and non-diabetic claudicant patients. The WELCH questionnaire is a useful tool in clinical practice for the evaluation of intermittent claudication treatment. Orv Hetil. 2020; 161(38): 1637-1645.


Assuntos
Cilostazol/uso terapêutico , Diabetes Mellitus/fisiopatologia , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/complicações , Qualidade de Vida/psicologia , Tetrazóis/uso terapêutico , Vasodilatadores/uso terapêutico , Idoso , Estudos de Casos e Controles , Complicações do Diabetes , Feminino , Humanos , Claudicação Intermitente/psicologia , Extremidade Inferior/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/tratamento farmacológico , Resultado do Tratamento , Caminhada
7.
J Stroke Cerebrovasc Dis ; 29(8): 104936, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689594

RESUMO

BACKGROUND: Non-stenotic intracranial and systemic atherosclerosis are associated with ischemic stroke. We report frequency and response to anticoagulant vs. antiplatelet prophylaxis of patients with embolic stroke of undetermined source (ESUS) who have non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis. METHODS: Exploratory analysis of the international NAVIGATE ESUS randomized trial comparing rivaroxaban 15mg daily with aspirin 100mg daily in 7213 patients with recent ESUS. Among participants with results of intracranial arterial imaging with either computed tomographic angiography (CTA) or magnetic resonance angiography (MRA), the frequency and predictors of non-stenotic intracranial and systemic atherosclerosis and responses to antithrombotic therapy were assessed. RESULTS: Among 4723 participants with available intracranial CTA or MRA results (65% of the trial cohort), the prevalence of intracranial atherosclerosis was 16% (n=739). Patient features independently associated with intracranial atherosclerosis included East Asian region (odds ratio 2.7, 95%CI 2.2,3.3) and cervical carotid plaque (odds ratio 2.3, 95%CI 1.9,2.7), among others. The rate of recurrent ischemic stroke averaged 4.8%/year among those with intracranial atherosclerosis vs. 5.0.%/year for those without (HR 0.95, 95%CI 0.65, 1.4). Among those with intracranial atherosclerosis, the recurrent ischemic stroke rate was higher if assigned to rivaroxaban (5.8%/year) vs. aspirin (3.7%/year), but the difference was not statistically significant (HR 1.6, 95%CI 0.78, 3.3). There was trend for the effect of antithrombotic treatments to be different according to the presence or absence of intracranial atherosclerosis (pinteraction=0.09). Among participants with evidence of systemic atherosclerosis by either history or imaging (n=3820), recurrent ischemic stroke rates were similar among those assigned to rivaroxaban (5.5%/year) vs. aspirin (4.9%/year)(HR 1.1, 95%CI 0.84, 1.5). CONCLUSIONS: East Asia region was the strongest factor associated with intracranial atherosclerosis. There were no statistically significant differences between rivaroxaban and aspirin prophylaxis for recurrent ischemic stroke in patients with non-stenotic intracranial atherosclerosis and/or systemic atherosclerosis.


Assuntos
Aspirina/administração & dosagem , Inibidores do Fator Xa/administração & dosagem , Fibrinolíticos/administração & dosagem , Arteriosclerose Intracraniana/tratamento farmacológico , Embolia Intracraniana/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Idoso , Aspirina/efeitos adversos , Método Duplo-Cego , Inibidores do Fator Xa/efeitos adversos , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Arteriosclerose Intracraniana/epidemiologia , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/epidemiologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/epidemiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Prevalência , Recidiva , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento
8.
Angiology ; 71(9): 773-790, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32638610

RESUMO

A systematic literature review was conducted to identify and summarize the clinical efficacy and safety of available antithrombotic therapies after peripheral endovascular or surgical revascularization in patients with peripheral artery disease (PAD). Five databases were searched using free-text and Emtree/Mesh terms for PAD, randomized controlled trials (RCTs), and antithrombotic therapies of interest (ie, single antiplatelet therapy, dual antiplatelet therapy, and vitamin K antagonists). Randomized controlled trials were eligible for inclusion if they assessed the risk of thrombotic events (ie, myocardial infarction, ischemic stroke, cardiovascular death, limb ischemia, or limb amputation) or safety profile (ie, minor, moderate, major, or fatal bleeding events) after revascularization. In total, 16 RCTs were identified. Only a few studies reported on treatment effects of the investigated therapies. Myocardial infarction, ischemic stroke, cardiovascular death, and amputation were reported in up to 2.3%, 2.3%, 5.6%, and 7.3% of patients, respectively. Bleeding events were observed in up to 8.4% (major) and 1.5% (fatal) of patients. Despite available treatments, patients with PAD undergoing revascularization remain at risk of thrombotic events. There is a need for new treatments that will help to optimize care for patients with symptomatic PAD undergoing revascularization.


Assuntos
Fibrinolíticos/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/cirurgia , Procedimentos Endovasculares , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
Eur J Vasc Endovasc Surg ; 60(3): 421-429, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32669223

RESUMO

OBJECTIVE: Optimal pharmacological treatment (OPT) for peripheral arterial occlusive disease (PAOD) includes prescription of lipid lowering drugs, antithrombotics, and antihypertensives to symptomatic patients affected by intermittent claudication or chronic limb threatening ischaemia. This study sought to determine sex disparities and time trends in prescription of OPT in this population (clinicaltrials.gov NCT03909022). METHODS: Using data from the second largest insurance fund in Germany, BARMER, data on patients with an index admission for symptomatic PAOD between 1 January 2010 and 30 June 2018 with follow up until the end of 2018 were analysed. Sex disparities in post-discharge prescription status six months after index admission were tested and adjusted for patient and healthcare variables using bivariable tests and logistic regression analysis. Time trends in the prescription prevalence of OPT were analysed and tested. RESULTS: There were 83 867 patients (mean age 71.9 years and 45.8% women) eligible for inclusion in the study. When compared with men, women had lower rates of prior outpatient care for PAOD (39.8% vs. 47.0%), were admitted more often with ischaemic rest pain (13.9% vs. 10.4%) and were older (74 vs. 70 y). After discharge, women had a lower rate of prescriptions for lipid lowering drugs (52.4% vs. 59.9%), while they received antihypertensive drugs more often (86.7% vs. 84.1%). We found evidence for a lower prescription prevalence of OPT in females (37.0% vs. 42.7%). Differences in patient and healthcare variables (e.g. demographics, comorbidities, prior treatment) between women and men explained 56% of this gap. The sex prescription gap did not narrow over time despite an overall upward trend in prescription prevalence for both women and men. CONCLUSION: Although presenting older and with more severe symptoms at the index admission for PAOD, women have a lower prescription prevalence of OPT compared with men, particularly with respect to lipid lowering drugs.


Assuntos
Demandas Administrativas em Assistência à Saúde , Anti-Hipertensivos/uso terapêutico , Fibrinolíticos/uso terapêutico , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/tendências , Hipolipemiantes/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Padrões de Prática Médica/tendências , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Prescrições de Medicamentos , Uso de Medicamentos/tendências , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/epidemiologia , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
10.
Am J Physiol Heart Circ Physiol ; 319(2): H456-H467, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32706261

RESUMO

Peripheral artery disease (PAD) is a manifestation of atherosclerosis in the leg arteries, which causes claudication. This may be in part due to vascular mitochondrial dysfunction and excessive reactive oxygen species (ROS) production. A mitochondrial-targeted antioxidant (MitoQ) has been shown to improve vascular mitochondrial function that, in turn, led to improved vascular function in older adults and animal models. However, the roles of vascular mitochondria in vascular function including endothelial function and arterial stiffness in patients with PAD are unknown; therefore, with the use of acute MitoQ intake, this study examined the roles of vascular mitochondria in endothelial function, arterial stiffness, exercise tolerance, and skeletal muscle function in patients with PAD. Eleven patients with PAD received either MitoQ or placebo in a randomized crossover design. At each visit, blood samples, brachial and popliteal artery flow-mediated dilation (FMD), peripheral and central pulse-wave velocity (PWV), blood pressure (BP), maximal walking capacity, time to claudication (COT), and oxygen utility capacity were measured pre- and-post-MitoQ and placebo. There were significant group by time interactions (P < 0.05) for brachial and popliteal FMD that both increased by Δ2.6 and Δ3.3%, respectively, and increases superoxide dismutase (Δ0.03 U/mL), maximal walking time (Δ73.8 s), maximal walking distance (Δ49.3 m), and COT (Δ44.2 s). There were no changes in resting heart rate, BP, malondialdehyde, total antioxidant capacity, PWV, or oxygen utility capacity (P > 0.05). MitoQ intake may be an effective strategy for targeting the vascular mitochondrial environment, which may be useful for restoring endothelial function, leg pain, and walking time in patients with PAD.NEW & NOTEWORTHY The results of this study reveal for the first time that acute oral intake of mitochondrial-targeted antioxidant (MitoQ, 80 mg) is effective for improving vascular endothelial function and superoxide dismutase in patients with peripheral artery disease (PAD). Acute MitoQ intake is also effective for improving maximal walking capacity and delaying the onset of claudication in patients with PAD. These findings suggest that the acute oral intake of MitoQ-mediated improvements in vascular mitochondria play a pivotal role for improving endothelial function, the redox environment, and skeletal muscle performance in PAD.


Assuntos
Antioxidantes/uso terapêutico , Artéria Braquial/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Tolerância ao Exercício/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Claudicação Intermitente/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Compostos Organofosforados/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Artéria Poplítea/efeitos dos fármacos , Ubiquinona/análogos & derivados , Idoso , Antioxidantes/metabolismo , Pressão Arterial/efeitos dos fármacos , Artéria Braquial/metabolismo , Artéria Braquial/fisiopatologia , Estudos Cross-Over , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/metabolismo , Claudicação Intermitente/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Contração Muscular/efeitos dos fármacos , Nebraska , Compostos Organofosforados/metabolismo , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/metabolismo , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/metabolismo , Artéria Poplítea/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Ubiquinona/metabolismo , Ubiquinona/uso terapêutico , Rigidez Vascular/efeitos dos fármacos , Caminhada
11.
Cardiovasc Ther ; 2020: 3057168, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32695228

RESUMO

Aims: Acetylsalicylic acid (ASA) is widely used for the prevention of atherothrombotic events in patients with chronic coronary artery disease (CAD) and peripheral artery disease (PAD), but the risk of vascular events remains high. We aimed at identifying randomised controlled trials (RCTs) on antithrombotic treatments in patients with chronic CAD or PAD. Methods: Searches were conducted on MEDLINE, EMBASE, and CENTRAL on March 1st, 2018. This systematic review (SR) uses a narrative synthesis to summarize the evidence for the efficacy and safety of antiplatelet and anticoagulant therapies in the population of both chronic CAD or PAD patients. Results: Four RCTs from 27 publications were included. Study groups included 15,603 to 27,395 patients. ASA alone was the most extensively studied (n = 3); other studies included rivaroxaban with or without ASA (n = 1), vorapaxar alone (n = 1), and clopidogrel with (n = 1) or without ASA (n = 1). Clopidogrel alone and clopidogrel plus ASA compared to ASA presented similar efficacy with comparable safety profile. Rivaroxaban plus ASA significantly reduced the risk of the composite of cardiovascular death, myocardial infarction, and stroke compared to ASA alone, although major bleeding with rivaroxaban plus ASA increased. Conclusion: There is limited and heterogeneous evidence on the prevention of atherothrombotic events in patients with chronic CAD or PAD. Clopidogrel alone and clopidogrel plus ASA did not demonstrate superiority over ASA alone. A combination of rivaroxaban plus ASA may offer significant additional benefit in reducing cardiovascular outcomes, yet it may increase the risk of bleeding, compared to ASA alone.


Assuntos
Anticoagulantes/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Trombose/prevenção & controle , Idoso , Anticoagulantes/efeitos adversos , Doença Crônica , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Terapia Antiplaquetária Dupla , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Trombose/diagnóstico , Trombose/epidemiologia , Resultado do Tratamento
12.
Arterioscler Thromb Vasc Biol ; 40(9): 1982-1989, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32673526

RESUMO

Atherosclerosis is a systemic disease that involves multiple vascular beds. The pathological characteristics and clinical presentation, however, vary among the different vascular territories. Acute coronary syndrome is a relatively common manifestation of coronary atherosclerotic disease, wherein the thrombosis occurs secondary to disruption (65%-75%) and erosion (25%-35%) of the fibrous caps of atheromatous plaques. The plaques associated with plaque rupture have large necrotic cores and thin and inflamed fibrous caps. However, the pathological manifestations of peripheral artery disease result from thrombosis regardless of the extent of atherosclerosis. Approximately 75% of peripheral arteries with significant stenosis demonstrate presence of thrombi, of which two-thirds have thrombi associated with insignificant atherosclerosis. The presence of obliterative thrombi in peripheral arteries of patients with critical limb ischemia in the absence of coronary artery-like lesions suggests a locally thrombogenic or remotely embolic basis of disease. Extensive calcification of the medial vascular layer is commonly observed. In this review, we have described and compared the pathological basis of coronary and peripheral artery disease in patients with acute coronary syndrome and critical limb ischemia. It is expected that pathogenetic characterization would allow for definition of strategic targets for superior management of peripheral artery disease.


Assuntos
Síndrome Coronariana Aguda/patologia , Artérias/patologia , Doença da Artéria Coronariana/patologia , Isquemia/patologia , Doença Arterial Periférica/patologia , Placa Aterosclerótica , Trombose/patologia , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/epidemiologia , Artérias/efeitos dos fármacos , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Vasos Coronários/patologia , Estado Terminal , Progressão da Doença , Fibrinolíticos/uso terapêutico , Fibrose , Humanos , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/epidemiologia , Prognóstico , Ruptura Espontânea , Trombose/tratamento farmacológico , Trombose/epidemiologia
13.
Expert Opin Pharmacother ; 21(13): 1603-1616, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32558590

RESUMO

INTRODUCTION: Peripheral artery disease (PAD) is a prevalent but underdiagnosed manifestation of atherosclerosis that has a worse prognosis than coronary artery disease. Patients with PAD are at heightened risk of both systemic cardiovascular adverse events and limb-related morbidity. There is insufficient awareness of its clinical manifestations, including intermittent claudication and critical limb ischemia and of its risk of adverse cardiovascular and limb outcomes. AREAS COVERED: The authors present the current knowledge concerning medications and their mechanism of action, landmark trials, and the evidence base behind the most commonly utilized pharmacological therapy including but not limited aspirin, clopidogrel, ticagrelor, warfarin, rivaroxaban, statins, angiotensin-converting enzyme inhibitors, Evolocumab and Ezetimibe. EXPERT OPINION: Relative to coronary artery disease, peripheral artery disease is an undertreated and under-investigated condition. The majority of the evidence base in the management of PAD is extrapolated from data subsets of large trials examining different conditions. This creates a paucity of management decisions based on trials powered for outcomes in PAD.


Assuntos
Anticoagulantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/sangue , Doença Arterial Periférica/etiologia , Fatores de Risco
14.
Am J Physiol Heart Circ Physiol ; 319(2): H320-H330, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32530751

RESUMO

The exercise pressor reflex is a feedback autonomic and cardiovascular control mechanism evoked by mechanical and metabolic signals within contracting skeletal muscles. The mechanically sensitive component of the reflex (the mechanoreflex) is exaggerated in patients with peripheral artery disease (PAD) and in a rat model of simulated PAD in which a femoral artery is chronically ligated. Products of cyclooxygenase enzyme activity have been shown to chronically sensitize the mechanoreflex in PAD, but the identity of the muscle afferent receptors that mediate the sensitization is unclear. We hypothesized that injection of the endoperoxide 4 receptor (EP4-R) antagonist L161982 or the thromboxane A2 receptor (TxA2-R) antagonist daltroban into the arterial supply of the hindlimb would reduce the pressor response to repetitive, dynamic hindlimb skeletal muscle stretch (a model of isolated mechanoreflex activation) in rats with a femoral artery that was ligated ~72 h before the experiment but not in rats with freely perfused femoral arteries. We found that EP4-R blockade had no effect on the pressor response (peak Δmean arterial pressure) to stretch in freely perfused (n = 6, pre: 14 ± 2, post: 15 ± 2 mmHg, P = 0.97) or ligated (n = 8, pre: 29 ± 4, post: 29 ± 6 mmHg, P = 0.98) rats. In contrast, TxA2-R blockade had no effect on the pressor response to stretch in freely perfused rats (n = 6, pre: 16 ± 3, post: 17 ± 4 mmHg, P = 0.99) but significantly reduced the response in ligated rats (n = 11, pre: 29 ± 4, post: 17 ± 5 mmHg, P < 0.01). We conclude that TxA2-Rs contribute to chronic mechanoreflex sensitization in the chronic femoral artery-ligated rat model of simulated PAD.NEW & NOTEWORTHY We demonstrate that thromboxane A2 receptors, but not endoperoxide 4 receptors, on the sensory endings of thin fiber muscle afferents contribute to the chronic sensitization of the muscle mechanoreflex in rats with a ligated femoral artery (a model of simulated peripheral artery disease). The data may have important implications for our understanding of blood pressure control during exercise in patients with peripheral artery disease.


Assuntos
Mecanorreceptores/metabolismo , Contração Muscular , Músculo Esquelético/inervação , Doença Arterial Periférica/metabolismo , Receptores de Tromboxano A2 e Prostaglandina H2/metabolismo , Reflexo , Animais , Pressão Arterial , Modelos Animais de Doenças , Masculino , Mecanorreceptores/efeitos dos fármacos , Mecanotransdução Celular , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/fisiopatologia , Fenilacetatos/farmacologia , Ratos Sprague-Dawley , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Receptores de Tromboxano A2 e Prostaglandina H2/antagonistas & inibidores , Reflexo/efeitos dos fármacos , Sulfonamidas/farmacologia , Fatores de Tempo
15.
Diab Vasc Dis Res ; 17(5): 1479164120930589, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32589047

RESUMO

BACKGROUND: In many cases, Ilomedin® infusions are applied as part of a perioperative measure in patients with peripheral arterial occlusive disease because it makes a relevant vasodilatatory effect in patients with type 2 diabetes mellitus and with/without peripheral neuropathy. AIMS: A prospective case-control study was performed to investigate the effect of prostanoids on peripheral resistance in patients with type 2 diabetes mellitus and patients without type 2 diabetes mellitus, as well as the role of peripheral neuropathy in patients undergoing arterial reconstruction. METHODS: Sixty patients undergoing arterial reconstruction were enrolled. Sufficient data were collected on 38 patients. Prior to surgery, peripheral nerve conduction velocity was measured. Blood flow volume at the common femoral artery was assessed intraoperatively using a Doppler flowmeter at four time points: at baseline before arterial reconstruction (T0), after reconstruction (T1), after 5 (T2) and 10 min (T3) after intra-arterial application of 3000 ng of Ilomedin. Peripheral resistance units were calculated as a function of mean arterial pressure and flow volume using the following formula: peripheral resistance unit = mean arterial pressure (mm Hg) / flow volume (mL/min). RESULTS: Ilomedin produced an immediate and significant drop of peripheral resistance in patients without type 2 diabetes mellitus as well as in patients with type 2 diabetes mellitus. Patients with peripheral neuropathy showed a less pronounced effect to Ilomedin compared to individuals with normal nerve conduction velocity.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Iloprosta/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/cirurgia , Resistência Vascular/efeitos dos fármacos , Procedimentos Cirúrgicos Vasculares , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Iloprosta/efeitos adversos , Infusões Intra-Arteriais , Cuidados Intraoperatórios , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Estudos Prospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Vasodilatadores/efeitos adversos , Adulto Jovem
16.
Lancet ; 395(10235): 1487-1495, 2020 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-32386592

RESUMO

BACKGROUND: Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. METHODS: In this systematic review and meta-analysis, all randomised trials comparing P2Y12 inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y12 inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I2 index. This study is registered with PROSPERO (CRD42018115037). FINDINGS: A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y12 inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y12 inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I2=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I2=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I2=0%), and vascular death (OR 0·97 [0·86-1·09]; I2=0%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I2=3·9%) did not differ between patients who received a P2Y12 inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y12 inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y12 inhibitor used. INTERPRETATION: Compared with aspirin monotherapy, P2Y12 inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y12 inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality. FUNDING: Italian Ministry of Education.


Assuntos
Aspirina/uso terapêutico , Aterosclerose/tratamento farmacológico , Clopidogrel/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Ticagrelor/uso terapêutico , Ticlopidina/uso terapêutico , Idoso , Aterosclerose/complicações , Transtornos Cerebrovasculares/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle
18.
N Engl J Med ; 382(21): 1994-2004, 2020 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-32222135

RESUMO

BACKGROUND: Patients with peripheral artery disease who have undergone lower-extremity revascularization are at high risk for major adverse limb and cardiovascular events. The efficacy and safety of rivaroxaban in this context are uncertain. METHODS: In a double-blind trial, patients with peripheral artery disease who had undergone revascularization were randomly assigned to receive rivaroxaban (2.5 mg twice daily) plus aspirin or placebo plus aspirin. The primary efficacy outcome was a composite of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes. The principal safety outcome was major bleeding, defined according to the Thrombolysis in Myocardial Infarction (TIMI) classification; major bleeding as defined by the International Society on Thrombosis and Haemostasis (ISTH) was a secondary safety outcome. RESULTS: A total of 6564 patients underwent randomization; 3286 were assigned to the rivaroxaban group, and 3278 were assigned to the placebo group. The primary efficacy outcome occurred in 508 patients in the rivaroxaban group and in 584 in the placebo group; the Kaplan-Meier estimates of the incidence at 3 years were 17.3% and 19.9%, respectively (hazard ratio, 0.85, 95% confidence interval [CI], 0.76 to 0.96; P = 0.009). TIMI major bleeding occurred in 62 patients in the rivaroxaban group and in 44 patients in the placebo group (2.65% and 1.87%; hazard ratio, 1.43; 95% CI, 0.97 to 2.10; P = 0.07). ISTH major bleeding occurred in 140 patients in the rivaroxaban group, as compared with 100 patients in the placebo group (5.94% and 4.06%; hazard ratio, 1.42; 95% CI, 1.10 to 1.84; P = 0.007). CONCLUSIONS: In patients with peripheral artery disease who had undergone lower-extremity revascularization, rivaroxaban at a dose of 2.5 mg twice daily plus aspirin was associated with a significantly lower incidence of the composite outcome of acute limb ischemia, major amputation for vascular causes, myocardial infarction, ischemic stroke, or death from cardiovascular causes than aspirin alone. The incidence of TIMI major bleeding did not differ significantly between the groups. The incidence of ISTH major bleeding was significantly higher with rivaroxaban and aspirin than with aspirin alone. (Funded by Bayer and Janssen Pharmaceuticals; VOYAGER PAD ClinicalTrials.gov number, NCT02504216.).


Assuntos
Aspirina/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Isquemia/prevenção & controle , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Terapia Combinada , Método Duplo-Cego , Quimioterapia Combinada , Procedimentos Endovasculares , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Hemorragia/epidemiologia , Humanos , Incidência , Isquemia/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/cirurgia , Inibidores da Agregação de Plaquetas/efeitos adversos , Rivaroxabana/efeitos adversos
19.
Eur J Vasc Endovasc Surg ; 59(4): 662-673, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32063462

RESUMO

OBJECTIVE: Findings from the Viborg Vascular (VIVA) trial show a mortality benefit of multi-faceted vascular screening which was mainly ascribed to the initiation of prophylactic medication. However, the pharmacological preventive potential, which exists when individuals have a positive screening test result and do not already use statins and anti-platelet agents, has not been analysed. The aim of this study was to investigate factors associated with a pharmacological preventive potential of statins and anti-platelet agents among attenders vascular screening for abdominal aortic aneurysm (AAA) and peripheral arterial disease (PAD). METHODS: This cross-sectional study used data from the VIVA trial screening arm including 25 074 men aged 64-75 years recruited between October 2008 and January 2011. Explanatory variables comprised socio-demographic- and socio-economic characteristics, comorbidities, medication use, and travel distance derived from nationwide registries. Outcomes included a positive screening test result, a pharmacological preventive potential, and attendance. Associations between the explanatory variables and the outcomes were investigated using the chi-square test and multivariate logistic regression. RESULTS: The factors most likely to be associated with a pharmacological preventive potential for positive AAA screening comprised age >70 years (odds ratio (OR) 1.23, 95% confidence interval 1.00-1.51), existing chronic obstructive pulmonary disease (COPD) (OR 2.22, 95% CI 1.38-3.57), and use of anti-hypertensives (OR 1.37, 95% CI 1.09-1.71). For positive PAD screening age >70 years (OR 1.41, 95% CI 1.25-1.60), living alone (OR 1.34, 95% CI 1.14-1.56), low income, COPD (OR 2.13, 95% CI 159-283), use of anti-hypertensives (OR 1.14, 95% CI 1.00-1.29) or anti-diabetics (OR 1.12, 95% CI 1.01-1.28), and short travel distance were associated with a pharmacological preventive potential. For combined vascular screening, age >70 years, living alone, low income, COPD, and use of anti-hypertensives were associated with a pharmacological preventive potential. Among these subgroups, lower attendance was associated with age >70 years, living alone, low income, COPD, and use of anti-diabetics. CONCLUSION: Future vascular screening programmes might benefit from tailoring information to subgroups who are more likely to benefit from screening but less likely to accept an offer.


Assuntos
Anti-Hipertensivos/uso terapêutico , Aneurisma da Aorta Abdominal/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Idoso , Aneurisma da Aorta Abdominal/epidemiologia , Comorbidade , Estudos Transversais , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Medição de Risco , Fatores de Risco
20.
SEMERGEN, Soc. Esp. Med. Rural Gen. (Ed. Impr.) ; 46(1): 16-26, ene.-feb. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-194403

RESUMO

OBJETIVO: Evaluar la persistencia al tratamiento y el uso de los recursos y sus costes en sujetos que inician tratamiento con clopidogrel de marca frente a genérico para el síndrome coronario agudo (SCA) y la enfermedad arterial periférica (EAP). PACIENTES Y MÉTODOS: Estudio observacional-retrospectivo, realizado a partir de los registros médicos de pacientes ≥18 años, que iniciaron un nuevo tratamiento con clopidogrel (marca vs. genérico) entre el 1 de abril de 2015 y el 31 de marzo de 2017. Se compararon 4 grupos de estudio y el seguimiento fue de un año. Principales medidas: comorbilidad, persistencia al tratamiento, ratio posesión-medicación (RPM) y uso de recursos y costes. Los resultados se analizaron mediante análisis multivariante, p < 0,05. RESULTADOS: Se compararon 4 grupos: a) SCA: clopidogrel-marca (n=1.067) vs. genérico (n=3.504); y b) EAP: clopidogrel-marca (n=425) vs. genérico (n=994). Para el SCA (edad media: 69,7 años; 61,4% hombres), con clopidogrel de marca, la persistencia (65,3% vs. 61,0%; p < 0,001); hazard-ratio ajustado 0,85 y el RPM (89,8% vs. 86,7%; p = 0,045) fueron superiores al genérico. El promedio/unitario del coste fue menor (2.890€ vs. 3.865€, p = 0,001).Para la EAP se observaron resultados similares con clopidogrel de marca, la persistencia (64,7% vs. 58,9%; p = 0,039), hazard-ratio ajustado 0,86 y el RPM (88,6% vs. 81,7%; p = 0,013) fueron superiores al genérico. El promedio/unitario del coste fue menor (2.880€ vs. 3.532€, p = 0,044). CONCLUSIONES: Los pacientes que inician tratamiento con clopidogrel de marca vs. genérico, tanto para el SCA como para el EAP, se asociaron a un mayor grado de adherencia al tratamiento, repercutiendo en unos menores costes sanitarios para el Sistema Nacional de Salud


OBJECTIVE: To evaluate the adherence to treatment, resource use, and costs in subjects initiating treatment with brand-name versus generic clopidogrel for acute coronary syndrome (ACS) and peripheral arterial disease (PAD). PATIENTS AND METHODS: Observational, retrospective study based on the medical records of patients aged ≥18 years who initiated treatment with clopidogrel (brand-name vs. generic) between 4 April 2015 and 31 March 2017. Four study groups were compared, and the follow-up was one year. The main measurements were: comorbidity, treatment adherence, medication possession ratio (MPR), resource use, and costs. The results were analysed using multivariate analysis. The level of statistical significance was P<.05. RESULTS: Four groups were compared: a) ACS: brand-name clopidogrel (N=1,067) vs. generic (N=3,504), and b) PAD: brand-name clopidogrel (N=425) vs. generic (N=994). In the ACS comparison (mean age: 69.7 years, 61.4% male), adherence (65.3% vs. 61.0%, P<.001), adjusted hazard ratio 0.85 and MPR (89.8% vs. 86.7%, P=.045) were more superior with brand-name clopidogrel than with the generic and with a lower mean cost per unit (€2,890 vs. €3,865, P=.001). In the PAD comparison, similar results were observed: persistence (64.7% vs. 58.9%, P=.039); adjusted hazard-ratio 0.86 and MPR (88.6% vs. 81.7%; P=.013) were more superior with brand-name clopidogrel than for the generic, with a lower mean cost per unit (€2,880 vs. €3,532, P=.044). CONCLUSIONS: There was better treatment adherence in patients initiating treatment with brand-name compared with generic clopidogrel for ACS and PAD, resulting in lower health costs for the Spanish National Health System


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Síndrome Coronariana Aguda/tratamento farmacológico , Clopidogrel/administração & dosagem , Medicamentos Genéricos/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Síndrome Coronariana Aguda/economia , Clopidogrel/economia , Medicamentos Genéricos/economia , Custos de Cuidados de Saúde , Adesão à Medicação/estatística & dados numéricos , Doença Arterial Periférica/economia , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/economia , Estudos Retrospectivos , Espanha
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