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1.
Clin Ter ; 170(5): e357-e363, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31612193

RESUMO

AIM OF THE STUDY: Cilostazol is a phosphodiesterase III inhibitor that has anti-inflammatory and immunomodulatory effects and can act with beneficial effect in Dry Eye Syndrome (DES). This clinical trial evaluates the effects of cilostazol on the tear film. MATERIALS AND METHODS: Following the run-in period, subjects were randomly into two groups: 40 subjects treated with cilostazol and 40 no-treated subjects. The Walking Impairment Questionnaire (WIQ) has been administered to all patients. RESULT: The data obtained from comparison of the two study groups A and B were, respectively, the following: Schirmer I: 10.2±0.2 Vs 13.8±0.4 (p< 0.001); Schirmer II: 3.8±0.1 Vs 4.6±0.2 (p<0.001); Break-up time (BUT) 4.2±0.3 Vs 6.5±0.2 (p<0.001) with disappearing of symptoms. The WIQ showed a significant difference in the walking distance (p<0.05) and calf pain severity (p<0.005) of treated patients. In comparison with the placebo group, treated patients showed an improvement (p<0.03) in calf pain severity. CONCLUSION: The administration of cilostazol was effective, in reducing DES and improve walking distance questionnaire.


Assuntos
Cilostazol/uso terapêutico , Síndromes do Olho Seco/tratamento farmacológico , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Vasodilatadores/uso terapêutico , Caminhada/fisiologia , Idoso , Síndromes do Olho Seco/etiologia , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/complicações , Inquéritos e Questionários , Resultado do Tratamento
2.
Angiol Sosud Khir ; 25(3): 29-37, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31503245

RESUMO

AIM: The study was aimed at assessing efficacy and safety of treatment with Aducil® (cilostazol) compared with Trental® 400 in patients with moderate-to-severe intermittent claudication due to peripheral atherosclerosis. PATIENTS AND METHODS: The study included a total of one hundred and forty-five 36-to-75-year-old patients. The participants were distributed into 2 groups according to the inclusion/exclusion criteria in a 2 to 1 proportion: patients in group 1 received Aducil® 100 mg BID, in group 2 - Trental® 400 TID for 12 weeks. 142 subjects completed the protocol. RESULTS: Analysis of the effectiveness of treatment according to the primary criterion showed a better effectiveness of Aducil® as compared with Trental® 400. Subjects who received Aducil® had a higher increase in the absolute maximum walking distance after 12 weeks of treatment as compared with those taking Trental® 400: 126±110 m versus 45±39 m, respectively (р<0.001). Subjects who received Aducil® had a statistically significant improvement in quality of life parameters such as physical and mental health components according to the SF-36 questionnaire after 12 weeks of treatment (р≤0.01). Subjects in Aducil® group had better quality of life with an increase from 34 to 40 points according to the physical component score, while patients in Trental® 400 group demonstrated minor positive changes (from 35 to 37 points); mean mental component score increased from 45 to 48 points in Aducil® group as compared with an increase from 45 to 47 points in Trental® 400 group. While self-reported physical health status was similar between the groups at baseline, subjects in Aducil® group reported better physical functioning after treatment (р=0.016). Two adverse events were registered in two subjects in Aducil® group. CONCLUSION: Analysis of the study endpoints demonstrated that Aducil® had better treatment effectiveness in patients with chronic lower limb ischemia stage IIB according to the classification of A.V. Pokrovsky-Fontaine as compared with Trental® 400, while the safety profile and drug tolerance were similar between the two.


Assuntos
Cilostazol , Claudicação Intermitente , Isquemia , Inibidores da Agregação de Plaquetas , Cilostazol/uso terapêutico , Humanos , Claudicação Intermitente/tratamento farmacológico , Isquemia/tratamento farmacológico , Extremidade Inferior , Inibidores da Agregação de Plaquetas/uso terapêutico , Qualidade de Vida , Caminhada
3.
J Zhejiang Univ Sci B ; 20(8): 687-692, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31273966

RESUMO

The objective of this study was to assess the angiogenic potential expressed as a quotient of vascular endothelial growth factor A (VEGF-A), as an indicator of proangiogenic activity, and the circulating receptors (soluble VEGF receptor protein R1 (sVEGFR-1) and sVEGFR-2), as indicators of the effect of angiogenic inhibition, depending on the concentrations of matrix metalloproteinase 2 (MMP-2) and MMP-9 and their tissue inhibitor 1 (TIMP-1) and TIMP-2 in the plasma of patients with lower extremity artery disease (LEAD). These blood parameters in patients with intermittent claudication (IC) and critical limb ischemia (CLI) were compared for select clinical and biochemical features. Stimulation of angiogenesis in the plasma of individuals with LEAD was evident as indicated by the significant increase in VEGF-A concentration along with reduced inhibition depending on circulating receptors sVEGFR-1 and sVEGFR-2. Critical ischemia was associated with higher VEGF-A, MMP-9, TIMP-1, and TIMP-2 concentrations than in the case of IC.


Assuntos
Claudicação Intermitente/sangue , Isquemia/sangue , Extremidade Inferior/irrigação sanguínea , Metaloproteinase 9 da Matriz/sangue , Neovascularização Patológica , Inibidor Tecidual de Metaloproteinase-1/sangue , Inibidor Tecidual de Metaloproteinase-2/sangue , Idoso , Inibidores da Angiogênese/farmacologia , Feminino , Regulação da Expressão Gênica , Humanos , Claudicação Intermitente/tratamento farmacológico , Isquemia/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/sangue
4.
Vasc Med ; 24(5): 414-421, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31277561

RESUMO

Extensive atherosclerotic plaque burden in the lower extremities often leads to symptomatic peripheral artery disease (PAD) including impaired walking performance and claudication. Interleukin-1ß (IL-1ß) may play an important pro-inflammatory role in the pathogenesis of this disease. Interruption of IL-1ß signaling was hypothesized to decrease plaque progression in the leg macrovasculature and improve the mobility of patients with PAD with intermittent claudication. Thirty-eight patients (mean age 65 years; 71% male) with symptomatic PAD (confirmed by ankle-brachial index) were randomized 1:1 to receive canakinumab (150 mg subcutaneously) or placebo monthly for up to 12 months. The mean vessel wall area (by 3.0 T black-blood magnetic resonance imaging (MRI)) of the superficial femoral artery (SFA) was used to measure plaque volume. Mobility was assessed using the 6-minute walk test. Canakinumab was safe and well tolerated. Markers of systemic inflammation (interleukin-6 and high-sensitivity C-reactive protein) fell as early as 1 month after treatment. MRI (32 patients at 3 months; 21 patients at 12 months) showed no evidence of plaque progression in the SFA in either placebo-treated or canakinumab-treated patients. Although an exploratory endpoint, placebo-adjusted maximum and pain-free walking distance (58 m) improved as early as 3 months after treatment with canakinumab when compared with placebo. Although canakinumab did not alter plaque progression in the SFA, there is an early signal that it may improve maximum and pain-free walking distance in patients with symptomatic PAD. Larger studies aimed at this endpoint will be required to definitively demonstrate this. ClinicalTrials.gov Identifier: NCT01731990.


Assuntos
Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Idoso , Anti-Inflamatórios/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Biomarcadores/sangue , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Feminino , Alemanha , Humanos , Mediadores da Inflamação/sangue , Claudicação Intermitente/sangue , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/fisiopatologia , Jordânia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Estudo de Prova de Conceito , Estudos Prospectivos , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
5.
Khirurgiia (Mosk) ; (3): 98-104, 2019.
Artigo em Russo | MEDLINE | ID: mdl-30938364

RESUMO

Peripheral artery disease is still one of the most important surgical problems. General surgeons treat the majority of patients with chronic lower limb ischemia due to the lack of specialized surgical care. Current methods for risk factors adjustment, exercise therapy and the most common drugs for intermittent claudication management are reviewed in the article. The effect of these medicines on subjective (pain-free walking distance, maximal walking distance, etc.) and objective (ankle-brachial index) parameters and the incidence of complications are analyzed.


Assuntos
Tratamento Conservador/métodos , Isquemia/terapia , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/terapia , Assistência Ambulatorial/métodos , Índice Tornozelo-Braço , Doença Crônica , Terapia por Exercício , Humanos , Claudicação Intermitente/tratamento farmacológico , Claudicação Intermitente/etiologia , Claudicação Intermitente/terapia , Isquemia/etiologia , Doença Arterial Periférica/complicações , Medição de Risco , Fatores de Risco , Federação Russa , Caminhada
6.
Am J Cardiovasc Drugs ; 19(2): 203-209, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30417231

RESUMO

INTRODUCTION: The Clinical and Endothelial Function Assessment after Endothelin Receptor Antagonist (CLAU) trial demonstrated the effect of bosentan on the endothelial function, inflammatory status and claudication distance in Hispanic patients with incipient peripheral arterial disease (PAD). Our aim was to assess the protective effect on cardiovascular events of bosentan versus conventional anti-atherosclerosis therapy. METHODS: CLAU included 56 patients with intermittent claudication, randomized 1:1 to receive bosentan for 12 weeks (n = 27) or placebo (n = 29), associating the best medical treatment. Log-rank and hazard ratio (HR) analyses were performed to estimate the relative efficacy of bosentan in preventing incidence of major adverse events (MAE) including target limb revascularization (TLR), amputation, myocardial infarction (MI), and all-cause death; major cardiovascular adverse events (MACE) including TLR, amputation, MI, stroke, and cardiovascular-cause death; and major adverse limb events (MALE), which combines TLR and amputation. RESULTS: During the follow-up period (34 ± 5 months), five MAE occurred in the control group only (17.2%), including two TLR, one amputation, one stroke, and an MI. The ratio of event-free survival for MAE to 3 years follow-up was higher in the group treated with bosentan (100% vs 66%, p = 0.01, HR = 76; 95% confidence interval 0.05-104,677, p = 0.24). A similar trend was observed in incidence of MACE (100% vs 66%, p = 0.01) and MALE (100% vs 80%, p = 0.15). CONCLUSION: Treatment with bosentan in the early low-to-mild stages of PAD may prevent cardiovascular events and the need for lower limb revascularization in the Hispanic population. Trial Registration ClinicalTrials.gov identifier NCT25102012.


Assuntos
Anti-Hipertensivos/uso terapêutico , Bosentana/uso terapêutico , Claudicação Intermitente/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Seguimentos , Hispano-Americanos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/tratamento farmacológico , Resultado do Tratamento
7.
Clin Biochem ; 64: 30-36, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30586555

RESUMO

OBJECTIVE: Aspirin is a widely used platelet inhibitor to prevent thrombotic events. However, in 25% of patients the antiplatelet effect is insufficient. The current study aimed to validate a newly developed PDW-miR92a-score as a biomarker of the individual response to aspirin enabling targeted antithrombotic therapy. METHODS: Blood samples were collected from 209 patients with intermittent claudication on daily aspirin therapy. Based on results from the arachidonic acid stimulated aggregation test, patients were defined as aspirin resistant (n = 92) or responders (n = 117). Using the cut-off values for platelet distribution width (PDW) and plasma levels of microRNA-92a (miR-92a) defined in our pilot study, we investigated the performance of the combined PDW-miR92a-score in the validation study. Furthermore, receiver operating characteristic curve analysis was performed in the validation cohort in order to optimize the cut-off values of the two score parameters. RESULTS: PDW and miR-92a levels were significantly higher in aspirin resistant compared to responding patients. When using the predefined cut-off values for PDW and miR-92a the combined PDW-miR92a score showed high specificity (93.1%) but poor sensitivity (19.8%) for aspirin resistance. By recalculation using new cut-off values identified in the validation cohort, a score with a specificity of 75% and a sensitivity of 54.9% was obtained. CONCLUSION: Both PDW and plasma levels of miR-92a were confirmed to be significantly higher in aspirin resistant compared to responding patients in our validation cohort. We were, however, unable to confirm the high sensitivity of the combined PDW-miR92a-score previously published by our group in a pilot study.


Assuntos
Aspirina/uso terapêutico , Plaquetas/citologia , Resistência a Medicamentos , Claudicação Intermitente/tratamento farmacológico , MicroRNAs/sangue , Inibidores da Agregação de Plaquetas/uso terapêutico , Testes de Função Plaquetária/métodos , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Agregação Plaquetária/efeitos dos fármacos , Testes de Função Plaquetária/normas , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Sensibilidade e Especificidade
8.
Am J Cardiol ; 123(5): 847-853, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30573159

RESUMO

Peripheral arterial disease (PAD) is an atherosclerotic process involving both modifiable and nonmodifiable risk factors. Prospective cohort studies show that patients with PAD have a 6-fold greater risk of death from cardiovascular disease than those without PAD. Currently, there is no effective treatment for PAD. The study was a randomized, placebo-controlled trial, involving 180 patients, aged 35 to 75. The subjects were divided into 2 groups. One group underwent 24 weeks of nutraceutical treatment consisting in the administration of 4 capsules of Annurca apple polyphenolic extract (AMS)/day. The placebo group was administered with identically appearing capsules containing only maltodextrin. Primary outcome measures were: walking autonomy, ankle-brachial index, acceleration time. In the AMS group, at the end of the treatment period, walking autonomy was increased on average by 69% (p <0.05), while slighter effects were registered as regards ankle-brachial index (+25%; p <0.05) and acceleration time (-3.6%; p <0.05), when compared with baseline. Placebo group revealed no significant differences as regards variations of all outcomes measures (p >0.05). Our preliminary results may indicate AMS product as a promising natural and safe tool for treatment of symptoms related to PAD.


Assuntos
Claudicação Intermitente/tratamento farmacológico , Malus/química , Doença Arterial Periférica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Administração Oral , Adulto , Idoso , Índice Tornozelo-Braço , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Estudos Prospectivos , Resultado do Tratamento , Caminhada
10.
Clin Cardiol ; 41(11): 1414-1422, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30284297

RESUMO

BACKGROUND: The ACC/AHA cholesterol guidelines recommend patients with peripheral artery disease (PAD) be treated with a moderate to high-intensity statin. The extent to which patients with new or worsening PAD symptoms are offered guideline therapy is unknown. HYPOTHESIS: There is significant variability in rate of guideline-directed statin intensification across clinical practices. METHODS: In the PORTRAIT registry, patterns of statin therapy were assessed in 1144 patients at 16 PAD specialty clinics between June 2011 and December 2015 before and after an evaluation for new or worsening claudication symptoms. We documented whether patients were treated with a guideline statin as well as the incidence of statin intensification. Statin intensification was defined as transitioning from no statin or low-intensity statin to moderate or high-intensity statin treatment. Patient factors associated with intensification were examined. Site and provider-level variation in intensification was summarized using an adjusted median odds ratio (aMOR). RESULTS: Among 1144 patients, 810 (70.8%) were initially on guideline therapy compared to 334 (29.2%) that were not. In the latter, 103 (30.8%) received intensification following evaluation. Patients with typical symptoms displayed greater odds of intensification (OR 3.74; 95% CI: 1.23-11.41) while older patients had lower odds of intensification (OR 0.60/decade; 95% CI: 0.41-0.88). Site variability for statin intensification was observed across sites (aMOR = 3.15; 95% CI 1.22-9.60, [P = 0.02]) but not providers (aMOR = 1.89; 95% CI 1.00-3.90, [P = 0.14]). CONCLUSIONS: Most patients evaluated at a PAD specialty clinic for new or worsening claudication symptoms arrived on guideline statin therapy. Only 31% not receiving appropriate therapy underwent statin intensification. These findings highlight an important opportunity to optimize medical therapy for patients with PAD.


Assuntos
Dislipidemias/tratamento farmacológico , Fidelidade a Diretrizes/normas , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Idoso , Austrália/epidemiologia , Progressão da Doença , Dislipidemias/diagnóstico , Dislipidemias/epidemiologia , Feminino , Humanos , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/epidemiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/epidemiologia , Estudos Prospectivos , Sistema de Registros , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
11.
Pharmacoepidemiol Drug Saf ; 27(9): 953-961, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30043552

RESUMO

PURPOSE: The purpose of the study is to evaluate the effectiveness of risk minimization measures-labeling changes and communication to health care professionals-recommended by the European Medicines Agency for use of cilostazol for the treatment of intermittent claudication in Europe. METHODS: Observational study of cilostazol in The Health Improvement Network (United Kingdom), EpiChron Cohort (Spain), SIDIAP (Spain), Swedish National Databases, and GePaRD (Germany). Among new users of cilostazol, we compared the prevalence of conditions targeted by the risk minimization measures in the periods before (2002-2012) and after (2014) implementation. Conditions evaluated were prevalence of smoking, cardiovascular conditions, concurrent use of ≥2 antiplatelet agents, concurrent use of potent CYP3A4/CYP2C19 inhibitors and high-dose cilostazol, early monitoring of all users, and continuous monitoring of users at high cardiovascular risk. RESULTS: We included 22 593 and 1821 new users of cilostazol before and after implementation of risk minimization measures, respectively. After implementation, the frequency of several conditions related to the labeling changes improved in all the study populations: prevalence of use decreased between 13% (EpiChron) and 57% (SIDIAP), frequency of cardiovascular contraindications decreased between 8% (GePaRD) and 84% (EpiChron), and concurrent use of high-dose cilostazol and potent CYP3A4/CYP2C19 inhibitors decreased between 6% (Sweden) and 100% (EpiChron). The frequency of other conditions improved in most study populations, except smoking, which decreased only in EpiChron (48% reduction). CONCLUSIONS: This study indicates that the risk minimization measures implemented by the EMA for the use of cilostazol have been effective in all European countries studied, except for smoking cessation before initiating cilostazol, which remains an area of improvement.


Assuntos
Doenças Cardiovasculares/epidemiologia , Cilostazol/efeitos adversos , Inibidores da Agregação de Plaquetas/efeitos adversos , Serviços Preventivos de Saúde/organização & administração , Fumar/epidemiologia , Idoso , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/prevenção & controle , Cilostazol/administração & dosagem , Bases de Dados Factuais/estatística & dados numéricos , Relação Dose-Resposta a Droga , Rotulagem de Medicamentos , Feminino , Alemanha/epidemiologia , Implementação de Plano de Saúde/estatística & dados numéricos , Humanos , Claudicação Intermitente/tratamento farmacológico , Claudicação Intermitente/etiologia , Claudicação Intermitente/prevenção & controle , Masculino , Inibidores da Agregação de Plaquetas/administração & dosagem , Prevalência , Serviços Preventivos de Saúde/métodos , Avaliação de Programas e Projetos de Saúde/estatística & dados numéricos , Fumar/efeitos adversos , Prevenção do Hábito de Fumar/métodos , Prevenção do Hábito de Fumar/organização & administração , Espanha/epidemiologia , Suécia/epidemiologia , Reino Unido/epidemiologia
12.
J Endovasc Ther ; 25(3): 306-312, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29706129

RESUMO

PURPOSE: To investigate the midterm safety and effectiveness of cilostazol treatment in claudicant patients undergoing endovascular therapy. METHODS: The Sufficient Treatment of Peripheral Intervention by Cilostazol (STOP-IC) study ( ClinicalTrials.gov identifier NCT00912756; University Hospital Medical Information Network identifier UMIN000002091) enrolled 200 patients (mean age 73 years; 131 men) treated for femoropopliteal disease from March 2009 to April 2011 at 13 cardiovascular centers in Japan. The participants were randomized 1:1 to receive oral aspirin with or without cilostazol. Of the 100 patients assigned to the 2 treatment groups, 7 patients in the cilostazol group and 2 patients in the no-cilostazol group were withdrawn from the study without undergoing endovascular treatment, leaving 93 patients in the cilostazol group and 98 patients in the no-cilostazol group for follow-up analysis. The primary outcome measure was primary patency; secondary outcome measures were freedom from clinically-driven target lesion revascularization (CD-TLR) and overall survival. Outcomes were analyzed on an intention-to-treat basis using the Kaplan-Meier method; estimates were compared with the log-rank test. RESULTS: The median follow-up was 38.1 months (interquartile range 25.1, 47.7). Among the 93 subjects in the cilostazol group, 7 died and 26 withdrew from administration 1 year after the endovascular procedure. Discontinuation of cilostazol was not a significant factor for restenosis. Primary patency was significantly higher in the cilostazol group than in the no-cilostazol group (69% vs 54%, p=0.026) at 3 years. The cilostazol group also had better 3-year freedom from CD-TLR (78% vs 63%, p=0.014), although overall survival estimates did not differ significantly (p=0.95). CONCLUSION: These results suggest that the safety and effectiveness of cilostazol treatment were sustained in patients with femoropopliteal disease undergoing endovascular treatment.


Assuntos
Angioplastia com Balão , Fármacos Cardiovasculares/administração & dosagem , Cilostazol/administração & dosagem , Artéria Femoral/efeitos dos fármacos , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/terapia , Artéria Poplítea/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/efeitos adversos , Cilostazol/efeitos adversos , Feminino , Artéria Femoral/fisiopatologia , Humanos , Claudicação Intermitente/fisiopatologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/fisiopatologia , Artéria Poplítea/fisiopatologia , Recidiva , Fatores de Risco , Stents , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular/efeitos dos fármacos
13.
J Vasc Surg ; 67(3): 910-921, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28259568

RESUMO

OBJECTIVE: We have previously shown that exogenous administration of the nuclear protein high mobility group box 1 (HMGB1) improves angiogenesis after tissue ischemia. Antagonizing HMGB1 prolongs muscle necrosis and deters regeneration. In this study, we evaluated HMGB1 expression in peripheral arterial disease (PAD) and the mechanisms that promote its release in a murine model of hindlimb ischemia. Specifically, we investigated how chloroquine (CQ), a commonly employed disease-modifying antirheumatic drug, promotes HMGB1 release from muscle. We hypothesized that CQ could increase HMGB1 locally and systemically, allowing it to mediate recovery from ischemic injury. METHODS: Muscle biopsies were performed on patients undergoing lower extremity surgery for non-PAD-related disease as well as for claudication and critical limb ischemia. Clinical symptoms and ankle-brachial indices were recorded for each patient. HMGB1 was detected in muscle sections using immunohistochemical staining. Unilateral femoral artery ligation was performed on both wild-type and inducible HMGB1 knockout mice. Wild-type mice were administered intraperitoneal CQ 2 weeks before and after femoral artery ligation. Laser Doppler perfusion imaging was used to determine perfusion recovery. Serum and tissue levels of HMGB1 were measured at designated time points. In vitro, cultured C2C12 myoblasts were treated with increasing doses of CQ. HMGB1, autophagosome formation, p62/SQSTM1 accumulation, caspase-1 expression and activity, and lactate dehydrogenase levels were measured in supernatants and cell lysates. RESULTS: Nuclear expression of HMGB1 was prominent in patients with claudication and critical limb ischemia (P < .05) compared with controls. CQ-treated mice had elevated serum HMGB1 and diffuse HMGB1 staining in muscle (P < .01). In wild-type mice, CQ treatment resulted in higher laser Doppler perfusion imaging ratios in the ischemic limb at 7 days (P < .03) and less fat replacement after 2 weeks (P < .03). In cultured myoblasts, CQ induced autophagosome accumulation, inhibited p62/SQSTM-1 degradation, and activated caspase-1. CONCLUSIONS: HMGB1 is prominently expressed in PAD muscle but mostly confined to the nucleus. Our in vivo data suggest that HMGB1 mobilization into the sarcoplasm and serum can be increased with CQ, possibly through caspase-1-mediated pathways. Whereas HMGB1 can be released by many cell types, these studies suggest that the muscle may be an important additional source that is relevant in PAD.


Assuntos
Cloroquina/farmacologia , Artéria Femoral/cirurgia , Proteína HMGB1/metabolismo , Claudicação Intermitente/tratamento farmacológico , Isquemia/tratamento farmacológico , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/efeitos dos fármacos , Doença Arterial Periférica/tratamento farmacológico , Idoso , Animais , Autofagia/efeitos dos fármacos , Velocidade do Fluxo Sanguíneo , Estudos de Casos e Controles , Caspase 1/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Feminino , Proteína HMGB1/deficiência , Proteína HMGB1/genética , Humanos , Claudicação Intermitente/metabolismo , Claudicação Intermitente/patologia , Isquemia/metabolismo , Isquemia/patologia , L-Lactato Desidrogenase/metabolismo , Ligadura , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Doença Arterial Periférica/metabolismo , Doença Arterial Periférica/patologia , Recuperação de Função Fisiológica , Fluxo Sanguíneo Regional , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
14.
Presse Med ; 47(1): 56-61, 2018 Jan.
Artigo em Francês | MEDLINE | ID: mdl-29273182

RESUMO

Medical management of peripheral arterial disease (PAD) patients is aimed at limb symptom relief and reducing systemic major adverse events risk. For the first purpose: exercise therapy is recommended in case of claudication; multidisciplinary evaluation for surgical options is mandatory in case of critical limb ischaemia. Reducing cardiac and stroke risk can be achieved through: statin prescription in most of the cases; antiplatelet agents in symptomatic PAD patients; cardio-vascular risk factors control.


Assuntos
Perna (Membro)/irrigação sanguínea , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Arteriosclerose Obliterante/tratamento farmacológico , Gerenciamento Clínico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Claudicação Intermitente/tratamento farmacológico , Isquemia/tratamento farmacológico , Isquemia/cirurgia , Educação de Pacientes como Assunto , Doença Arterial Periférica/complicações , Doença Arterial Periférica/cirurgia , Inibidores da Agregação de Plaquetas/uso terapêutico , Fatores de Risco , Acidente Vascular Cerebral/prevenção & controle , Trombofilia/tratamento farmacológico , Trombofilia/etiologia , Enxerto Vascular/métodos
15.
s.l; s.n; 2018. ilus, tab.
Não convencional em Espanhol | BRISA/RedTESA | ID: biblio-905547

RESUMO

CONTEXTO: El buflomedil comenzó a comercializarse en el año 1974, para el tratamiento sintomático de la claudicación intermitente causada por la obstrucción de las arterias de los miembros inferiores. En 2006, el Ministerio de Salud francés tomó una serie de medidas, basadas en las investigaciones realizadas por las áreas de farmacovigilancia, que revelaron casos graves asociados al uso de buflomedil, tales como trastornos neurológicos (mioclonía, convulsiones y estado epiléptico) y cardiovasculares (hipotensión, trastornos del ritmo y paro cardíaco), uso inapropiado (incumplimiento de la indicación y/o contraindicaciones, inadecuada dosificación, uso en pacientes con insuficiencia renal) y casos de intoxicación voluntaria, principalmente en adultos jóvenes. TECNOLOGÍA: IFA: BUFLOMEDIL Código ATC: C04AX20 Categoría Terapéutica: vasodilatador periférico. El buflomedil es un vasodilatador que aumenta el flujo sanguíneo en el cerebro y otras partes del organismo. Está indicado en el tratamiento de: -Los síntomas de la arteriopatía oclusiva periférica (AOP en estadio II) que genera claudicación intermitente; -Fenómeno de Raynaud, que es una afección causada por espasmos vasculares desencadenados por bajas temperaturas o emociones fuertes que bloquean el flujo sanguíneo a las extremidades, orejas y nariz; -Accidente Cerebro Vascular Isquémico (ACVI). OBJETIVO: Evaluar la seguridad y eficacia del buflomedil para el tratamiento del accidente cerebrovascular isquémico, la claudicación intermitente y el fenómeno de Raynaud. BÚSQUEDA Y ANÁLISIS DE LA EVIDENCIA CIENTÍFICA: Se realizó una búsqueda en MEDLINE, NICE, INHATHA, Portal salud Madrid, BIREME, Universidad York, PROSPERO, EPISTEMONIKOS, Brisa, LILACS, Trip, Base de datos ensayos clínicos OMS, Clinical trials.gov, DOAJ, RedETSA, IACS, Embase, Instituto Carlos III, Osteba, Revista Nature, búsqueda manual y en las Agencias Regulatorias de Japón, Australia, EE.UU., Canadá, Uruguay, Brasil y Chile. La estrategia de búsqueda fue buflomedil, en humanos, lenguaje restringido a inglés y español, teniendo en cuenta los estudios publicados desde 1998 hasta el 10 abril 2018. Para la realización de este informe se incluyeron 3 metaanálisis (MA), una serie de casos y un informe de EMA. RESULTADOS: Eficacia: Fenómeno de Raynaud (FR): El MA de Stewart5 et al (2012) incluyó numerosos estudios para el tratamiento de este fenómeno, pero sólo una ICCA (Investigación Clínica Controlada Aleatorizada) para buflomedil (Le Quintrec6 , 1991) que incorporó 31 participantes con FR primario, aleatorizados en dos ramas a recibir buflomedil 300 mg dos veces por día o placebo, con un seguimiento de seis meses. Se midió frecuencia y severidad de FR. Los participantes presentaron una frecuencia basal para este fenómeno de 24 ataques por semana en ambos grupos. Luego de la intervención, la diferencia en la frecuencia de ataques semanales entre ambos grupos favoreció a buflomedil con una diferencia de medias (DM) -8,82 IC95% -17,55 a -0,09, el intervalo de confianza fue amplio y cerca de la línea de no discriminación. La DM, en el score de severidad del fenómeno de Raynaud, también resultó a favor de buflomedil, pero no fue estadísticamente significativa (DM -0,41 IC95% -0,84 a 0,02). Consideramos que la calidad de evidencia de este estudio resultó baja según el sistema Grade, por imprecisión debido al bajo tamaño muestral y a los amplios intervalos de confianza. Claudicación Intermitente (CI): El MA de deBacker7 et al (2013) incluyó dos ICCAs para el tratamiento de la CI, con 127 participantes que recibieron buflomedil oral comparado con placebo. Los puntos finales evaluados fueron la distancia de caminata libre de dolor (DCLD) y la distancia máxima de caminata (DMC), las que se analizaron mediante una prueba de ejercicio estandarizada. Los autores determinaron que la evidencia para evaluar la eficacia de buflomedil fue escasa. Las 2 ICCAs incluidas mostraron resultados moderadamente positivos a favor del buflomedil; esto se ve menoscabado por el sesgo de publicación (los autores refirieron que al menos 4 estudios no fueron publicados). El estudio de Trübesteinet8 et al (1984) (N=113; 20 abandonaron el tratamiento) fue bien diseñado, con una duración del seguimiento de 12 semanas. La Diferencia Ponderada de Medias (DPM) para la distancia de caminata libre de dolor fue de 75,1 m IC95% 20,6 a 129,6 y para la distancia máxima de caminata la DPM 80,7 m IC95% 9,4 a 152. El estudio de Diamantopulus9 et al (2001), que incluyó participantes diabéticos (N=40; 6 abandonaron) con CI, tuvo un seguimiento de 6 meses. La DPM para la distancia de caminata libre de dolor fue 80,6 m IC95% 3 a 158,2 y para la distancia máxima de caminata la DPM fue 171,4 m IC95% 51,3 a 291,5. Ambas ICCAs mostraron significación estadística en pacientes que utilizaron buflomedil, tanto para DCLD como para DMC; sin embargo, mostraron amplios intervalos de confianza. Consideramos que estos dos estudios poseen muy baja calidad, tal como se aprecia en la siguiente tabla. Cabe destacar que los autores excluyeron gran número de estudios por su mala calidad. Accidente cerebrovascular isquémico (ACVI): El MA de Wu10 et al (2015) evaluó 26 ICCAs (N=2756) realizados en China. Los estudios incluyeron pacientes hospitalizados durante los primeros días luego de la presentación clínica del ACVI. La media de edad fue de 58 a 75 años. La mayoría de los ICCAs administraron buflomedil intravenoso, con una dosis diaria de 200 mg durante 14 días. El punto final primario fue mortalidad o discapacidad a largo plazo (3 meses). Además, los autores reportaron mortalidad y discapacidad a corto plazo (al finalizar el tratamiento con buflomedil). Los puntos finales secundarios fueron: mejoría del déficit neurológico y seguridad. Para el punto final primario se incluyó el estudio de Cui et al (2005) (N=200), por ser el único que reportó muerte y discapacidad a largo plazo (3 meses). Los sobrevivientes de ACVI tratados con buflomedil presentaron menor riesgo de sufrir el resultado combinado muerte o discapacidad a largo plazo que aquellos en el grupo control (N=200; RR 0,71, IC95% 0,53 a 0,94). La mortalidad en el grupo con buflomedil a los 3 meses de seguimiento, fue 14% versus 15% en el grupo control (RR 0,93 IC95% 0,48 a 1,83). El grupo buflomedil presentó una incidencia de discapacidad a los 3 meses de 27% versus 43% en el grupo control (RR 0,63 IC95% 0,42 a 0,93), siendo ésta una diferencia estadísticamente significativa. También se incluyeron 8 estudios (Bu 2010; Chen 2002a; Dong 2004; Lu 2003; Niu 2008, Pan 2007; Qian 2006; Yang 2012) con 1.056 participantes que reportaron mortalidad a corto plazo y un estudio (Li, 2008) con 85 participantes que reportó discapacidad a corto plazo. La mortalidad a corto plazo fue evaluada en ocho estudios, de los cuales los autores tomaron sólo cuatro (Pan, 2007; Chen 2002a; Qian 2006; Lu 2003) para realizar la revisión del MA, que no demostró diferencia en el riesgo de muerte entre ambos tratamientos (buflomedil N=369 vs control N=362; RR 0,45 IC95% 0,14 a 1,46; I2= 0%). La discapacidad a corto plazo fue evaluada en un estudio (Li, 2008) que comparó buflomedil N=44 vs control N=41, mediante el índice de Barthel. Informaron una DM 15 IC95% 5,83 a 24,17 en el grupo buflomedil que sugiere mejor resultado. Respecto al punto final secundario, se incluyeron 26 estudios con 2.756 participantes que reportaron déficit neurológico. No se encontró evidencia robusta para ninguno de los resultados analizados. Dado que no se pudo acceder a los estudios primarios, el análisis de calidad de evidencia no pudo ser realizado por este Programa. Sin embargo, los investigadores del MA determinaron que la calidad de evidencia fue baja, de acuerdo a los principios de Grade por presencia de sesgos, falta de cegamiento y enmascaramiento, sesgo de publicación e imprecisión por bajo tamaño muestral y amplios intervalos de confianza. DISCUSIÓN: De acuerdo a la evidencia presentada anteriormente, los investigadores encontraron resultados moderadamente positivos a favor del buflomedil en el tratamiento del fenómeno de Raynaud, la claudicación intermitente y el accidente cerebrovascular isquémico. Sin embargo, la baja o muy baja calidad metodológica, el pequeño tamaño muestral, los amplios intervalos de confianza y el sesgo de publicación debilitan la estimación del efecto para los puntos finales analizados. Por otra parte, el uso de buflomedil se asocia a EA cardiológicos (principalmente taquicardia, hipotensión, trastornos del ritmo ventricular y paro cardíaco) y neurológicos (principalmente convulsiones, mioclonía y estado epiléptico) que ocurren bajo condiciones terapéuticas, especialmente en pacientes de edad avanzada que son la principal población para la cual se encuentra indicado. Estos riesgos se ven agravados por el hecho de que buflomedil es un fármaco con un índice terapéutico estrecho, lo cual requiere adaptación/ajuste de la dosis para la función renal. Este tópico es de particular importancia en la práctica asistencial, pues de lo contrario se podría generar una toxicidad que pondría en riesgo la vida del paciente.


Assuntos
Humanos , Claudicação Intermitente/tratamento farmacológico , Doença de Raynaud/tratamento farmacológico , Receptores Adrenérgicos alfa , Acidente Vascular Cerebral/tratamento farmacológico , Vasodilatadores/uso terapêutico , Análise Custo-Benefício , Avaliação da Tecnologia Biomédica
16.
J Am Heart Assoc ; 6(7)2017 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-28711864

RESUMO

BACKGROUND: The relative benefit of higher statin dosing in patients with peripheral artery disease has not been reported previously. We compared the effectiveness of low- or moderate-intensity (LMI) versus high-intensity (HI) statin dose on clinical outcomes in patients with peripheral artery disease. METHODS AND RESULTS: We reviewed patients with symptomatic peripheral artery disease who underwent peripheral angiography and/or endovascular intervention from 2006 to 2013 who were not taking other lipid-lowering medications. HI statin use was defined as atorvastatin 40-80 mg or rosuvastatin 20-40 mg. Baseline demographics, procedural data, and outcomes were retrospectively analyzed. Among 909 patients, 629 (69%) were prescribed statins, and 124 (13.6%) were treated with HI statin therapy. Mean low-density lipoprotein level was similar in patients on LMI versus HI (80±30 versus 87±44 mg/dL, P=0.14). Demographics including age (68±12 versus 67±10 years, P=0.25), smoking history (76% versus 80%, P=0.42), diabetes mellitus (54% versus 48%, P=0.17), and hypertension (88% versus 89%, P=0.78) were similar between groups (LMI versus HI). There was a higher prevalence of coronary artery disease (56% versus 75%, P=0.0001) among patients on HI statin (versus LMI). After propensity weighting, HI statin therapy was associated with improved survival (hazard ratio for mortality: 0.52; 95% confidence interval, 0.33-0.81; P=0.004) and decreased major adverse cardiovascular events (hazard ratio: 0.58; 95% confidence interval 0.37-0.92, P=0.02). CONCLUSIONS: In patients with peripheral artery disease who were referred for peripheral angiography or endovascular intervention, HI statin therapy was associated with improved survival and fewer major adverse cardiovascular events compared with LMI statin therapy.


Assuntos
Atorvastatina/administração & dosagem , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Claudicação Intermitente/tratamento farmacológico , Isquemia/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Rosuvastatina Cálcica/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Amputação , Angiografia , Atorvastatina/efeitos adversos , Biomarcadores/sangue , Estado Terminal , Progressão da Doença , Intervalo Livre de Doença , Prescrições de Medicamentos , Dislipidemias/sangue , Dislipidemias/diagnóstico por imagem , Dislipidemias/mortalidade , Procedimentos Endovasculares , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Claudicação Intermitente/sangue , Claudicação Intermitente/diagnóstico por imagem , Claudicação Intermitente/mortalidade , Isquemia/sangue , Isquemia/diagnóstico por imagem , Isquemia/mortalidade , Estimativa de Kaplan-Meier , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/mortalidade , Padrões de Prática Médica/tendências , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Rosuvastatina Cálcica/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
18.
PLoS One ; 12(6): e0178713, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28575088

RESUMO

BACKGROUND: It has been suggested that anti-hypertensive medications may worsen leg ischemia in peripheral artery disease (PAD) patients. We undertook a meta-analysis to assess the effect of anti-hypertensive medications on measures of leg ischemia including maximum walking distance (MWD), pain free walking distance (PFWD) and ankle brachial pressure index (ABPI). A meta-regression was performed to evaluate whether the effect of the anti-hypertensive medications on mean arterial pressure (MAP) was associated with changes in ABPI, MWD or PFWD. METHOD: A systematic literature search was performed to identify placebo controlled randomized control trials (RCT) testing anti-hypertensive medications, which reported baseline and follow-up measurements of: MAP and MWD, PFWD or ABPI in patients with intermittent claudication (IC) due to PAD. RESULT: A meta-analysis was performed on 5 RCTs comprising a total of 180 and 127 patients receiving anti-hypertensive medications and placebo respectively. This analysis suggested that anti-hypertensive medication did not significantly affect MWD, PFWD or ABPI. In contrast, the meta-regression analysis showed that the reduction in MAP due to the anti-hypertensive drugs was positively correlated with increased MWD during follow-up (ß = 8.371, p = 0.035). Heterogeneity across studies, as assessed by I2, was high. The follow-up period within the included trials was generally short with 3 out of 5 studies having a follow-up period of ≤ 6 weeks. CONCLUSION: This study suggests that anti-hypertensive treatment does not worsen but may improve leg ischemia in PAD patients. Larger multicenter trials with longer anti-hypertensive treatment periods are required to clarify the effect of anti-hypertensives on leg ischemia in PAD patients.


Assuntos
Anti-Hipertensivos/efeitos adversos , Isquemia/etiologia , Perna (Membro)/irrigação sanguínea , Doença Arterial Periférica/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Índice Tornozelo-Braço , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Humanos , Claudicação Intermitente/tratamento farmacológico , Claudicação Intermitente/etiologia , Isquemia/tratamento farmacológico , Dor/etiologia , Caminhada
19.
Cochrane Database Syst Rev ; 6: CD011741, 2017 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-28594443

RESUMO

BACKGROUND: Peripheral artery disease (PAD) is associated with a high clinical and socioeconomic burden. Treatments to alleviate the symptoms of PAD and decrease the risks of amputation and death are a high societal priority. A number of growth factors have shown a potential to stimulate angiogenesis. Growth factors delivered directly (as recombinant proteins), or indirectly (e.g. by viral vectors or DNA plasmids encoding these factors), have emerged as a promising strategy to treat patients with PAD. OBJECTIVES: To assess the effects of growth factors that promote angiogenesis for treating people with PAD of the lower extremities. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Specialised Register (June 2016) and CENTRAL (2016, Issue 5). We searched trial registries for details of ongoing or unpublished studies. We also checked the reference lists of relevant publications and, if necessary, tried to contact the trialists for details of the studies. SELECTION CRITERIA: We included randomised controlled trials comparing growth factors (delivered directly or indirectly) with no intervention, placebo or any other intervention not based on the growth factor's action in patients with PAD of the lower extremities. The primary outcomes were limb amputation, death and adverse events. The secondary outcomes comprised walking ability, haemodynamic measures, ulceration and rest pain. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and assessed the risk of bias. We used outcomes of the studies at low risk of bias for the main analysis and of all studies in the sensitivity analyses. We calculated odds ratios (OR) for dichotomous outcomes and mean differences for continuous outcomes with 95% confidence intervals (CI). We evaluated statistical heterogeneity using the I2 statistic and Cochrane's Q test. We conducted meta-analysis for the overall effect and for each growth factor as a subgroup analysis using OR in a fixed-effect model. We evaluated the robustness of the results in a sensitivity analysis using risk ratio (RR) and/or a random-effects model. We also assessed the quality of the evidence for each outcome. MAIN RESULTS: We included 20 trials in the review and used 14 studies (on approximately 1400 participants) with published results in the analyses. Six published studies compared fibroblast growth factors (FGF), four studies hepatocyte growth factors (HGF) and another four studies vascular endothelial growth factors (VEGF), versus placebo or no therapy. Six of these studies exclusively or mainly investigated participants with intermittent claudication and eight studies exclusively participants with critical limb ischaemia. Follow-up generally ranged from three months to one year. Two small studies provided some data at 2 years and one of them also at 10 years.The direction and size of effects for growth factors on major limb amputations (OR 0.99, 95% CI 0.71 to 1.38; 10 studies, N = 1075) and death (OR 0.99, 95% CI 0.69 to 1.41; 12 studies, N = 1371) at up to two years are uncertain. The quality of the evidence is low due to risk of bias and imprecision (at one year, moderate-quality evidence due to imprecision). However, growth factors may decrease the rate of any limb amputations (OR 0.56, 95% CI 0.31 to 0.99; 6 studies, N = 415). The quality of the evidence is low due to risk of bias and selective reporting.The direction and size of effects for growth factors on serious adverse events (OR 1.09, 95% CI 0.79 to 1.50; 13 studies, N = 1411) and on any adverse events (OR 1.10, 95% CI 0.73 to 1.64; 4 studies, N = 709) at up to two years are also uncertain. The quality of the evidence is low due to risk of bias and imprecision (for serious adverse events at one year, moderate-quality evidence due to imprecision).Growth factors may improve haemodynamic measures (low-quality evidence), ulceration (very low-quality evidence) and rest pain (very low-quality evidence) up to one year, but they have little or no effect on walking ability (low-quality evidence). We did not identify any relevant differences in effects between growth factors (FGF, HGF and VEGF). AUTHORS' CONCLUSIONS: The results of this review do not support the use of therapy with the growth factors FGF, HGF or VEGF in people with PAD of the lower extremities to prevent death or major limb amputation or to improve walking ability. However, the use of these growth factors may improve haemodynamic measures and decrease the rate of any limb amputations (probably due to preventing minor amputations) with an uncertain effect on adverse events; an improvement of ulceration and rest pain is very uncertain. New trials at low risk of bias are needed to generate evidence with more certainty.


Assuntos
Fatores de Crescimento de Fibroblastos/uso terapêutico , Fator de Crescimento de Hepatócito/uso terapêutico , Claudicação Intermitente/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/uso terapêutico , Amputação/estatística & dados numéricos , Fatores de Crescimento de Fibroblastos/efeitos adversos , Fator de Crescimento de Hepatócito/efeitos adversos , Humanos , Claudicação Intermitente/mortalidade , Perna (Membro)/irrigação sanguínea , Perna (Membro)/cirurgia , Úlcera da Perna/tratamento farmacológico , Doença Arterial Periférica/mortalidade , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator A de Crescimento do Endotélio Vascular/efeitos adversos
20.
J Vasc Surg ; 66(1): 275-280, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28533077

RESUMO

Peripheral artery disease (PAD) is common and associated with significant morbidity and mortality. Optimal medical management of PAD is required for each patient, irrespective of the decision regarding lower extremity revascularization. The goals include reducing cardiovascular morbidity and mortality and improving quality of life. The approach should consist of aggressive and individualized risk factor modification including smoking cessation, antiplatelet therapy, a statin, and an angiotensin-converting enzyme inhibitor. Exercise is critical for cardiovascular health and highly effective for improving claudication symptoms. Cilostazol may be considered for symptomatic treatment in certain patients.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Claudicação Intermitente/tratamento farmacológico , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/tratamento farmacológico , Comorbidade , Quimioterapia Combinada , Humanos , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/mortalidade , Claudicação Intermitente/fisiopatologia , Estilo de Vida , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Qualidade de Vida , Fatores de Risco , Comportamento de Redução do Risco , Resultado do Tratamento
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