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1.
Medicine (Baltimore) ; 98(46): e17266, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31725602

RESUMO

OBJECTIVE: The aim of our study was to assess the efficacy and safety of sarpogrelate hydrochloride by comparing the effects of sarpogrelate with conventional treatment on the improvement of symptoms in PAD patients. METHODS: The search was conducted in PubMed, Embase, Cochrane library database, CNKI, CBM for relevant randomized controlled trials (RCTs) before January 1st, 2019. Inclusion and exclusion of studies, assessment of quality, outcome measures, data extraction and synthesis were completed by two reviewers independently. The meta-analysis was performed with RevMan 5.3. RESULTS: Totally, 12 eligible RCTs were included in our analysis. Comparing the results of sarpogrelate group and control group, sarpogrelate significantly improved ankle-brachial index (ABI) levels (SMD = 0.05, [95%CI 0.20 to 0.74, P = .0005]), dorsalis pedis artery blood flow (MD = 0.16, [95%CI 0.09 to 0.23, P < .001]) and pain-free walking distance (PFWD) (MD = 201.86, [95%CI 9.34 to 394.38, P = .04]). The pooled analysis showed that a significant decrease in hsCRP (MD = -0.57, [95%CI -1.12 to -0.02, P = .04]) and IL-6 (MD = 1.48,[95%CI 0.39 to 2.56, P = .008]) was observed in the sarpogrelate treatment. CONCLUSION: Sarpogrelate was effective for improving the symptoms of PAD and showed good tolerability without significant adverse events.


Assuntos
Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Antagonistas da Serotonina/uso terapêutico , Succinatos/uso terapêutico , Adulto , Idoso , Índice Tornozelo-Braço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
2.
Gastroenterology ; 157(3): 682-691.e2, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152740

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.


Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Rivaroxabana/administração & dosagem , Idoso , Aspirina/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Método Duplo-Cego , Esquema de Medicação , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/efeitos adversos , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
3.
J Cardiovasc Surg (Torino) ; 60(4): 439-449, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31062571

RESUMO

Drug-eluting stent (DES) are the mainstay therapy for the treatment of coronary artery disease. Stent design and drug-elution strategies have evolved over the years leading to the last generation DES which shows optimal safety and efficacy outcome. Peripheral arteries have different mechanical and biological features and the lessons learned from the coronary field have been difficult to introduce into the development of peripheral vascular technologies. First, due to its complex biomechanical behavior the use of metallic stents is limited in some vascular segments (i.e., distal superficial fermoral artery [SFA]). Also, peripheral vascular atherosclerosis is different containing higher levels of plaque burden and calcium. Finally, peripheral arterial disease tends to be more aggressive including longer lesions and higher incidence of total chronic occlusion. In general terms, restenosis in the peripheral vascular territory is more aggressive and occurs at a later time (~12 months) requiring a different pharmacokinetic profile compared to coronary technologies. Several strategies have been evaluated in the peripheral arteries raging from the bare metal stent to the drug coated balloon and drug eluting stent with outcome varying depending on the different field of application (i.e. SFA and below-the-knee). Results coming from the clinical trial are encouraging but further studies and direct comparison among the different technologies are demanded to determine the best therapy for peripheral vascular disease.


Assuntos
Paclitaxel/administração & dosagem , Doença Arterial Periférica/terapia , Sirolimo/administração & dosagem , Stents , Sistemas de Liberação de Medicamentos , Stents Farmacológicos , Everolimo/administração & dosagem , Artéria Femoral/cirurgia , Humanos , Doença Arterial Periférica/tratamento farmacológico , Polímeros , Prevenção Secundária/métodos , Serina-Treonina Quinases TOR/antagonistas & inibidores
4.
Dtsch Med Wochenschr ; 144(10): 683-689, 2019 05.
Artigo em Alemão | MEDLINE | ID: mdl-31083738

RESUMO

Peripheral arterial occlusive disease is a frequent and chronic vascular disorder mostly affecting the lower limbs and caused by fibrous plaques in arteries that can result in stenoses and thrombi. Patients suffering from this condition show a high risk for cardiovascular complications of the complete arterial vascular system, especially post-procedural. Thus, there is a need to optimize anti-thrombotic therapy. Data on multiple antiplatelet aggregation therapy including new drug classes are expected in the coming years. In addition, recent studies showed that direct oral anticoagulation provided clinical advantages combined with a reasonable safety profile. Management of risk factors such as overweight and nicotine and correction of metabolic disorders are not to be ignored and the background to further therapy. All treating physicians should be aware of these aspects to guarantee an optimal care and motivation of their patients.


Assuntos
Anticoagulantes , Doença Arterial Periférica , Inibidores da Agregação de Plaquetas , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Humanos , Segurança do Paciente , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/epidemiologia , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Gestão de Riscos
6.
Angiology ; 70(8): 726-736, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30871330

RESUMO

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder predisposing affected individuals to lifelong low-density lipoprotein cholesterol (LDL-C) elevation and coronary heart disease. However, whether HeFH increases the risk of peripheral arterial disease (PAD) and ischemic stroke is undetermined. We examined associations between HeFH and these outcomes in a comprehensive systematic review and meta-analysis. We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, and PubMed (for ahead-of-print publications) for relevant English-language studies. Maximally adjusted risk estimates were pooled under random- and fixed-effects meta-analysis to derive odds ratios (ORs) and 95% confidence intervals (CIs). We included 6 studies representing 183 388 participants. Heterozygnous familial hypercholesterolemia was associated with a higher risk of PAD (OR: 3.59 [95% CI: 1.30-9.89]). This trend was nonsignificantly preserved (OR: 2.96 [95% CI: 0.68-12.88]) in sensitivity analyses of genetically defined HeFH. Genetic HeFH was not associated with increased ischemic stroke risk (OR: 0.76 [95% CI: 0.37-1.58]) although possessing an LDL-C >4.9 mmol/L (190 mg/dL) was (OR: 1.42 [95% CI: 1.06-1.89]). We found clinical and genetic diagnoses of HeFH to be associated with increased PAD risk. Genetically confirmed HeFH may not confer an increased risk of ischemic stroke. Modest associations may exist between LDL-C and ischemic stroke risk in HeFH.


Assuntos
Isquemia Encefálica/genética , Doença das Coronárias/genética , Hipercolesterolemia/genética , Doença Arterial Periférica/genética , Anticolesterolemiantes/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Humanos , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Doença Arterial Periférica/complicações , Doença Arterial Periférica/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/genética
7.
Vasc Med ; 24(2): 132-140, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30799766

RESUMO

Patients with peripheral artery disease (PAD) are at high risk for ischemic cardiovascular complications. While single antiplatelet therapy (SAPT), predominantly aspirin, has long been the standard antithrombotic treatment in stable PAD, there have now been greater than 40,000 PAD patients randomized to varying antiplatelet and/or anticoagulant regimens. In this review, we provide a summary of the current evidence for antithrombotics in stable PAD, focusing on the rates of major adverse cardiovascular events (MACE), major adverse limb events (MALE), and major bleeding. SAPT has a limited role in the treatment of asymptomatic PAD, particularly in the absence of concomitant coronary artery disease. In symptomatic PAD, SAPT is effective in preventing MACE, though treatment with a thienopyridine appears marginally superior to aspirin. Dual antiplatelet therapy (DAPT) suggests benefit over SAPT in reducing MACE and MALE, though studies to date are not conclusive and/or are associated with excess major bleeding. Combining moderate to high intensity vitamin K antagonists with antiplatelet therapy does not reduce MACE or MALE and increases life-threatening bleeding. Rivaroxaban 2.5 mg BID in addition to aspirin reduces the incidence of both MACE and MALE as compared to aspirin alone, without increasing life-threatening bleeding. This regimen is associated with a reduced severity of MALE when it does occur. Comparisons across antithrombotic trials in PAD are challenging given the heterogeneity of patient populations and the differing assessment of outcomes. The vascular medicine practitioner can reduce ischemic cardiac and limb events, as well as minimize life-threatening bleeding, by choosing the optimal antithrombotic regimen in their PAD patients.


Assuntos
Anticoagulantes/uso terapêutico , Fibrinolíticos/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Anticoagulantes/efeitos adversos , Tomada de Decisão Clínica , Quimioterapia Combinada , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Seleção de Pacientes , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Inibidores da Agregação de Plaquetas/efeitos adversos , Fatores de Risco , Resultado do Tratamento
8.
J Vasc Surg ; 69(6): 1924-1935, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30777693

RESUMO

OBJECTIVE: Previous studies have shown that hydrogen sulfide (H2S) exerts potent proangiogenic properties under in vitro conditions and in rodent models. We sought to determine whether a novel H2S prodrug promotes peripheral revascularization in a swine model of acute limb ischemia (ALI). METHODS: ALI was induced in 17 female miniswine via intravascular occlusion of the external iliac. At day 7 after ALI induction, miniswine (n = 17) were randomized to received placebo or the H2S prodrug, SG-1002 (800 mg per os twice a day), for 35 days. At day 35 SG-1002 increased circulating levels of H2S (5.0 ± 1.2 µmol/L vs 1.8 ± 0.50 µmol/L; P < .05), sulfane sulfur (10.6 ± 2.3 µmol/L vs 2.6 ± 0.8 µmol/L; P < .05), and nitrite (0.5 ± 0.05 µmol/L vs 0.3 ± 0.03 µmol/L; P < .005) compared with placebo. SG-1002 therapy increased angiographic scoring in ischemic limb vessel number (27.6 ± 1.6 vs 22.2 ± 1.8; P < .05) compared with placebo. Treatment with SG-1002 preserved existing capillaries in ischemic limbs (128.3 ± 18.7 capillaries/mm2 vs 79.0 ± 9.8 capillaries/mm2; P < .05) compared with placebo. Interestingly, treatment with SG-1002 also improved coronary vasorelaxation responses to bradykinin and substance P in miniswine with ALI. CONCLUSIONS: Our results suggest that daily administration of the H2S prodrug, SG-1002, leads to an increase in circulating H2S and nitric oxide signaling and preserves vessel number and density in ischemic limbs. Furthermore, SG-1002 therapy improved endothelial-dependent coronary artery vasorelaxation in the setting of ALI. Our data demonstrate that SG-1002 preserves the vascular architecture in ischemic limbs and exerts vascular protective effects in the coronary vasculature in a model of peripheral vascular disease.


Assuntos
Indutores da Angiogênese/farmacologia , Extremidades/irrigação sanguínea , Sulfeto de Hidrogênio/farmacologia , Isquemia/tratamento farmacológico , Neovascularização Fisiológica/efeitos dos fármacos , Doença Arterial Periférica/tratamento farmacológico , Pró-Fármacos/farmacologia , Doença Aguda , Indutores da Angiogênese/sangue , Indutores da Angiogênese/farmacocinética , Animais , Vasos Coronários/efeitos dos fármacos , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Feminino , Sulfeto de Hidrogênio/sangue , Sulfeto de Hidrogênio/farmacocinética , Isquemia/sangue , Isquemia/fisiopatologia , Óxido Nítrico/sangue , Nitritos/sangue , Estresse Oxidativo/efeitos dos fármacos , Doença Arterial Periférica/sangue , Doença Arterial Periférica/fisiopatologia , Pró-Fármacos/farmacocinética , Fluxo Sanguíneo Regional , Transdução de Sinais , Suínos , Porco Miniatura , Vasodilatação/efeitos dos fármacos
9.
Ann Vasc Surg ; 58: 166-173.e4, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30771465

RESUMO

BACKGROUND: Vascular surgeons have a central role in managing peripheral artery disease (PAD). This study assessed their knowledge, attitudes, and behaviors regarding pharmacologic risk reduction in PAD and results were compared to a similar 2004 survey conducted by our group. METHODS: An online questionnaire was administered to 161 active members of the Canadian Society for Vascular Surgery. RESULTS: Forty-eight participants (30%) completed the survey. Recommended targets for low-density lipoprotein cholesterol, blood pressure, and glucose were known by 52%, 38%, and 50% of vascular surgeons, respectively. Almost all participants recognized antiplatelet dosages and statin indications, but less than half could identify indications (29%) and precautions (44%) for angiotensin converting enzyme (ACE) inhibitor therapy. A majority (58%) routinely evaluate risk factors in <50% of their patients. Most vascular surgeons regularly provide risk reduction counseling, but less than 10% initiate or modify antihypertensive or ACE inhibitor therapy. Compared to 2004, knowledge of targets and indications/precautions for common cardiovascular medications and frequency of risk factor assessment have not changed. Rates of counseling for diabetes control and statin prescription have improved, but remain suboptimal. Regarding newer medications with cardiovascular benefit, less than 10% would prescribe proprotein convertase subtilisin/kexin type 9 and sodium-glucose cotransporter 2 inhibitors if they were available. The majority of vascular surgeons rate their PAD risk reduction knowledge as average and support an up-to-date Canadian PAD guideline. Most participants believe that risk reduction therapy is best provided by family physicians and internists, but also acknowledge that vascular surgeons should be well-versed in assessing and managing risk factors in PAD. CONCLUSIONS: Significant knowledge and action gaps exist among Canadian vascular surgeons with regards to pharmacologic cardiovascular risk reduction in PAD. Although there is recognition that vascular surgeons are central to the medical management of patients with PAD, few routinely evaluate risk factors and prescribe medications. There is little evidence of sufficient improvement since 2004. New educational and clinical strategies are needed to improve PAD risk reduction pharmacotherapy among Canadian vascular surgeons.


Assuntos
Anti-Hipertensivos/uso terapêutico , Atitude do Pessoal de Saúde , Diabetes Mellitus/tratamento farmacológico , Dislipidemias/tratamento farmacológico , Conhecimentos, Atitudes e Prática em Saúde , Hipertensão/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Cirurgiões/psicologia , Anti-Hipertensivos/efeitos adversos , Canadá , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Dislipidemias/sangue , Dislipidemias/diagnóstico , Pesquisas sobre Serviços de Saúde , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Hipoglicemiantes/efeitos adversos , Hipolipemiantes/efeitos adversos , Doença Arterial Periférica/sangue , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Lacunas da Prática Profissional , Prognóstico , Medição de Risco , Fatores de Risco , Sociedades Médicas
10.
Circ Res ; 124(3): 416-425, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30702997

RESUMO

Although acetylsalicylic acid is of proven benefit for secondary prevention in patients with cardiovascular disease, the risk of recurrent ischemic events remains high. Intensification of antithrombotic therapy with more potent antiplatelet drugs, dual antiplatelet therapy, or vitamin K antagonists further reduces the risk of major adverse cardiovascular events compared with acetylsalicylic acid alone but increases the risk of bleeding without reducing mortality. In patients with prior coronary artery disease or peripheral arterial disease the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial revealed that compared with acetylsalicylic acid alone, dual pathway inhibition with low-dose rivaroxaban (2.5 mg twice-daily), an oral factor Xa inhibitor, plus acetylsalicylic acid reduced major adverse cardiovascular event by 24%, major adverse limb events by 47%, and mortality by 18%. Major bleeding was increased by 70%, but there was no increase in fatal or intracranial bleeding. This article (1) reviews the results of the COMPASS trial, (2) explains why dual pathway inhibition is superior to antiplatelet or anticoagulant therapy alone, (3) compares the results with rivaroxaban plus aspirin with those with other antithrombotic regimens, and (4) provides insight into how best to apply the COMPASS results into practice.


Assuntos
Aspirina/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Fibrinolíticos/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Aspirina/efeitos adversos , Fibrilação Atrial/complicações , Doença Crônica , Doença da Artéria Coronariana/tratamento farmacológico , Quimioterapia Combinada/métodos , Inibidores do Fator Xa/administração & dosagem , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Recidiva , Projetos de Pesquisa , Rivaroxabana/administração & dosagem , Prevenção Secundária , Acidente Vascular Cerebral/prevenção & controle
12.
Circulation ; 139(9): 1134-1145, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30667279

RESUMO

BACKGROUND: Strokes were significantly reduced by the combination of rivaroxaban plus aspirin in comparison with aspirin in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies). We present detailed analyses of stroke by type, predictors, and antithrombotic effects in key subgroups. METHODS: Participants had stable coronary artery or peripheral artery disease and were randomly assigned to receive aspirin 100 mg once daily (n=9126), rivaroxaban 5 mg twice daily (n=9117), or rivaroxaban 2.5 mg twice daily plus aspirin (n=9152). Patients who required anticoagulation or had a stroke within 1 month, previous lacunar stroke, or intracerebral hemorrhage were excluded. RESULTS: During a mean follow-up of 23 months, fewer patients had strokes in the rivaroxaban plus aspirin group than in the aspirin group (83 [0.9% per year] versus 142 [1.6% per year]; hazard ratio [HR], 0.58; 95% CI, 0.44-0.76; P<0.0001). Ischemic/uncertain strokes were reduced by nearly half (68 [0.7% per year] versus 132 [1.4% per year]; HR, 0.51; 95% CI, 0.38-0.68; P<0.0001) by the combination in comparison with aspirin. No significant difference was noted in the occurrence of stroke in the rivaroxaban alone group in comparison with aspirin: annualized rate of 0.7% (HR, 0.82; 95% CI, 0.65-1.05). The occurrence of fatal and disabling stroke (modified Rankin Scale, 3-6) was decreased by the combination (32 [0.3% per year] versus 55 [0.6% per year]; HR, 0.58; 95% CI, 0.37-0.89; P=0.01). Independent predictors of stroke were prior stroke, hypertension, systolic blood pressure at baseline, age, diabetes mellitus, and Asian ethnicity. Prior stroke was the strongest predictor of incident stroke (HR, 3.63; 95% CI, 2.65-4.97; P<0.0001) and was associated with a 3.4% per year rate of stroke recurrence on aspirin. The effect of the combination in comparison with aspirin was consistent across subgroups with high stroke risk, including those with prior stroke. CONCLUSIONS: Low-dose rivaroxaban plus aspirin is an important new antithrombotic option for primary and secondary stroke prevention in patients with clinical atherosclerosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01776424.


Assuntos
Aspirina/administração & dosagem , Doença da Artéria Coronariana , Doença Arterial Periférica , Rivaroxabana/administração & dosagem , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/epidemiologia , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
13.
Vascular ; 27(3): 318-323, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30563434

RESUMO

OBJECTIVES: To determine the indications for the use, potential benefits, and adverse reactions of alprostadil in a group of Colombian patients. METHODS: A retrospective cross-sectional study was conducted in patients diagnosed with critical limb ischemia who received alprostadil in five hospitals in Colombia between September 2011 and July 2017. We reviewed the clinical records of each patient to obtain the sociodemographic and pharmacological variables, clinical stages, complications, comorbidities, reported effectiveness and adverse reactions. RESULTS: Sixty-one patients treated with alprostadil were evaluated; 50.8% of patients were men, and the average age of 72.5 ± 10.7 years. A total of 86.9% of patients were hypertensive, and 65.6% were diabetic. A total of 77.0% presented ulceration, and this condition was considered as a diabetic foot in 57.4% of patients. A total of 81.9% of patients were classified as Fontaine stage 4; 60.7% received therapy as initially indicated, with an average of 19 days of alprostadil use. Regarding the therapy results, 58.0% of the patients with ulcers or trophic lesions showed improvement, 86.2% showed improvement of pain, and the limb was saved in 72.1% of patients. CONCLUSIONS: Critical limb ischemia was presented by patients with advanced age and high cardiovascular risk who were treated during severe and advanced stages where therapeutic options are limited. Treatment with alprostadil achieved satisfactory results with improvement in ulcers, pain, and limb salvage rates in this series of patients.


Assuntos
Alprostadil/administração & dosagem , Isquemia/tratamento farmacológico , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/tratamento farmacológico , Vasodilatadores/administração & dosagem , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Alprostadil/efeitos adversos , Colômbia , Estado Terminal , Estudos Transversais , Bases de Dados Factuais , Feminino , Humanos , Isquemia/diagnóstico , Isquemia/fisiopatologia , Salvamento de Membro , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/fisiopatologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular/efeitos dos fármacos , Vasodilatadores/efeitos adversos
14.
J Vasc Surg ; 69(3): 944-951, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30591299

RESUMO

OBJECTIVE: Current prevention of peripheral vascular disease (PVD) focuses on blood pressure control, lipid lowering, and platelet inhibition with statins and aspirin. A critical role for inflammation in the pathophysiology of atherosclerosis has been established for decades and, although both statins and aspirin have anti-inflammatory properties, the management of inflammation is becoming increasingly recognized. Here, we summarize recent clinical and translational discoveries that outline how inflammation may become targeted in PVD in the future. METHODS: A PubMed search using a combination of the following MeSH terms-inflammation, pathophysiology, atherosclerosis, cancer, auto immune disease, therapy, and clinical trial-was performed and literature selected with a focus on basic pathophysiology of inflammation and clinical investigations targeting inflammation in cardiovascular disease, cancer, and autoimmune diseases. RESULTS: Based on this literature overview, we summarized the common features of inflammation in these different diseases and how inflammation may also translate into common therapeutic strategies. Finally, the results of recent clinical and translational investigations highlighting inflammation in cardiovascular disease are reviewed with a focus on hematopoietic mutations that generate more active immune cells and increase cardiovascular risk, treatment with anti-inflammatory biological pharmaceuticals that reduce cardiovascular risk, and translational studies demonstrating how the treatment of defective immune-mediated clearance of dying cells in lesions may prevent disease progression. CONCLUSIONS: Progress in clinical and translational atherosclerosis research has now brought inflammation in clinical focus, because recent discoveries with respect to cardiovascular risk prediction and pharmacotherapy targeting inflammation have shown the potential to improve future care of patients with PVD.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artérias/efeitos dos fármacos , Aterosclerose/tratamento farmacológico , Mediadores da Inflamação/antagonistas & inibidores , Inflamação/tratamento farmacológico , Doença Arterial Periférica/tratamento farmacológico , Animais , Artérias/metabolismo , Artérias/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Humanos , Inflamação/metabolismo , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Terapia de Alvo Molecular , Doença Arterial Periférica/metabolismo , Doença Arterial Periférica/patologia , Placa Aterosclerótica , Transdução de Sinais/efeitos dos fármacos
15.
Stroke ; 49(12): 2953-2960, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30571405

RESUMO

Background and Purpose- Current guidelines recommend prescription of a number of medications to prevent cardiovascular events in patients with peripheral artery disease (PAD). The impact that these medications have on the incidence of stroke in PAD patients has not been thoroughly investigated. This study aimed to investigate the association of prescription of antihypertensive drugs, antiplatelet medications, and statins, as well as cardiovascular disease risk factors, with stroke incidence in patients with symptoms of PAD. Methods- A database search was completed to identify studies reporting the incidence of stroke and prescription of antihypertensive drugs, antiplatelet medications, and statins in patients with PAD symptoms. A random-effects model was used to meta-analyze the incidence of stroke in patients with symptoms of PAD and in subgroups with intermittent claudication and critical limb ischemia. Metaregression was performed to explore the association between the incidence of stroke and the prescription of medications and the presence of cardiovascular disease risk factors. Results- Twelve studies including 67 915 patients with symptoms of PAD were included. A meta-analysis of data from 7 studies demonstrated an incidence of stroke of 1.31 per 100 patient-years. Patients with critical limb ischemia experienced stroke 2.3× more frequently than those with intermittent claudication (95% CI, 1.58-3.36; P<0.01). The reported prescription of antihypertensive agents varied between 10% and 71%, antiplatelet drugs between 49% and 90%, and statins between 11% and 79% in different studies. Metaregression suggested an association between a lower incidence of stroke and the prescription of antiplatelet drugs ( R2=0.81, P<0.01), and statins ( R2=0.85, P<0.01), but not antihypertensives medications. A prior history of cerebrovascular events was associated with a higher incidence of stroke ( R2=0.58, P<0.05). Conclusions- This review supports previous research which suggests the need for more effective means of ensuring more widespread prescription of preventative medications in patients with PAD.


Assuntos
Anti-Hipertensivos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Acidente Vascular Cerebral/epidemiologia , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/epidemiologia , Humanos , Incidência , Doença Arterial Periférica/epidemiologia , Análise de Regressão , Prevenção Secundária
16.
Curr Pharm Des ; 24(38): 4511-4515, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30585539

RESUMO

BACKGROUND: Peripheral artery disease is a common manifestation of systemic atherosclerosis which strongly correlates to cardiovascular morbidity and mortality. In addition, the progression of peripheral artery disease leads to an increased risk of limb loss. In order to reduce these events, the benchmark of treatment and research over the last years has been the antiplatelet therapy which aims at inhibition of platelet aggregation. Over the last years, new studies combining antiplatelet agents in different therapeutic schemes have been proven efficacious. Unfortunately, patients remain still at high risk of CV events. Novel Oral Anticoagulants have been introduced as alternatives to warfarin, in the prevention and treatment of venous thromboembolism. The rationale of using medication which acts on platelet activation and the coagulation pathway of thrombosis has led investigators to examine the role of Noac's in preventing CV events in patients with peripheral artery disease, stable or unstable. METHODS: The aim of this study is to review the current evidence with respect to recently published studies concerning the use of Novel anticoagulants in peripheral artery disease. RESULTS: The Compass trial has shown that a combination of rivaroxaban with traditional therapy may produce promising results in reducing amputation rates, stroke, cardiac events, and mortality, however, there are still safety issues with bleeding requiring acute care. The ePAD study has provided us with insight concerning safety and efficacy after peripheral angioplasty or stenting and actually the need for further research. The Voyager Pad study, following the steps of Compass, is studying the effect and safety of the addition of rivaroxaban to traditional therapy in the highest risk population aka patients undergoing peripheral revascularization. The evidence concerning patients with concomitant atrial fibrillation appears to be insufficient, however, recent guidelines propose the use of novel oral anticoagulants. CONCLUSION: For the time being, novel oral anticoagulants in combination with aspirin may provide an alternative treatment in PAD, however, it is deemed necessary to identify patient subgroups who will benefit the most.


Assuntos
Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Clopidogrel/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Administração Oral , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Clopidogrel/administração & dosagem , Clopidogrel/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Resultado do Tratamento
17.
J Am Coll Cardiol ; 72(25): 3274-3284, 2018 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-30573030

RESUMO

BACKGROUND: Diabetes confers an increased risk for atherosclerotic cardiovascular disease, but less is known about the independent risk diabetes confers on major cardiovascular and limb events in patients with symptomatic peripheral artery disease (PAD) on contemporary management. OBJECTIVES: The authors sought to assess the risk of cardiovascular and limb events in patients with PAD and diabetes as compared with those with PAD alone. METHODS: In the EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) trial, 13,885 patients with symptomatic PAD were evaluated with a primary endpoint of an adjudicated composite of major adverse cardiovascular events (MACE) (cardiovascular death, myocardial infarction, ischemic stroke) followed over a median of ∼30 months. The diabetes subgroup was analyzed compared with the subgroup without diabetes, and further examined for diabetes-specific factors such as glycosylated hemoglobin (HbA1c) that might affect risk for major cardiovascular and limb outcomes. RESULTS: A total of 5,345 patients (38.5%) had diabetes; the majority (n = 5,134 [96.1%]) had type 2 diabetes. The primary endpoint occurred in 15.9% of patients with PAD and diabetes as compared with 10.4% of those without diabetes (absolute risk difference 5.5%; adjusted hazard ratio: 1.56; 95% confidence interval [CI]: 1.41 to 1.72; p < 0.001). Every 1% increase in HbA1c was associated with a 14.2% increased relative risk for MACE (95% CI: 1.09 to 1.20; p < 0.0001). CONCLUSIONS: Patients with PAD and diabetes are at high risk for cardiovascular and limb ischemic events, even on contemporary therapies. Every 1% increase in HbA1c was associated with a 14.2% increased relative risk for MACE (95% CI: 1.09 to 1.20; p < 0.0001). (A Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease [EUCLID]; NCT01732822).


Assuntos
Diabetes Mellitus Tipo 2/mortalidade , Isquemia/mortalidade , Extremidade Inferior/irrigação sanguínea , Doença Arterial Periférica/mortalidade , Inibidores da Agregação de Plaquetas/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Isquemia/diagnóstico , Isquemia/tratamento farmacológico , Extremidade Inferior/patologia , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/tratamento farmacológico , Resultado do Tratamento
18.
Int Heart J ; 59(5): 1041-1046, 2018 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-30101855

RESUMO

The prevalence of arteriosclerosis obliterans (ASO) and critical limb ischemia (CLI) is currently increasing, and arterial reconstruction is often attempted to salvage the limb. Some patients cannot undergo attempted revascularization because of contraindications, and they only receive conservative treatment. In this study, we investigate the comorbidities and survival rates of patients with CLI who receive conservative treatment. Thirty-five patients with CLI due to ASO, who had not undergone revascularization surgery (C group), were enrolled. As controls, 136 patients with CLI due to ASO who did undergo revascularization (R group), mainly via bypass surgery, were enrolled. Coronary artery disease, heart failure, and respiratory dysfunction were factors indicating conservative treatment. Limb salvage rates and survival rates were not significantly different between the two groups. Patients who had survived for less than two years after surgery had a higher prevalence of chronic heart failure, cardiovascular disease, and end-stage renal disease compared to patients who had survived for more than two years. The use of statins, dual antiplatelets, aspirin, or warfarin did not influence whether a patient survived for longer than two years. 77% of patients survived for more than two years after receiving only conservative therapies. Surgical revascularization did not improve the prognosis of patients with CLI as compared with the conservative therapy. Clinicians might start with conservative treatment while considering other treatment options for patients with CLI.


Assuntos
Arteriosclerose Obliterante/epidemiologia , Tratamento Conservador/métodos , Salvamento de Membro/métodos , Extremidade Inferior/patologia , Doença Arterial Periférica/patologia , Idoso , Idoso de 80 Anos ou mais , Arteriosclerose Obliterante/complicações , Doenças Cardiovasculares/epidemiologia , Comorbidade , Tratamento Conservador/estatística & dados numéricos , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Isquemia/patologia , Falência Renal Crônica/epidemiologia , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/cirurgia , Prevalência , Resultado do Tratamento
19.
Dtsch Med Wochenschr ; 143(15): 1060-1064, 2018 08.
Artigo em Alemão | MEDLINE | ID: mdl-30060273

RESUMO

Patients with peripheral artery disease are at high-risk for cardiovascular events. Anti-thrombotic treatment is very important for secondary prevention. In symptomatic patients single antiplatelet therapy with clopidogrel or Aspirin is recommended. After peripheral revascularisation transient dual antiplatelet therapy is widely used although there is only little evidence. Following peripheral bypass surgery most patients are treated with single antiplatelet therapy, in some cases (prostetic bypass grafts) dual antiplated therapy can be useful and selected patients with complex venous grafts might profit from anticoagulation with vitamin K antagonists.The recent publication of the COMPASS (Cardiovascular OutcoMes for People Using Anticoagulation StrategieS) study showed relevant reduction of MACE (Major Adverse Cariac Events) and MALE (Major Adverse Limb Events) for the combined therapy of rivaroxaban 2 × 2,5 mg compared to Aspirin 100 mg with increased risk for gastrointestinal bleeding. In the current VOYAGER PAD (Vascular Outcomes Study of Aspirin along with Rivaroxaban in Endovascular or Surgical Limb Revascularization for PAD) study this concept is tested after peripheral revascularisation.


Assuntos
Fibrinolíticos/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Administração Oral , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Implante de Prótese Vascular , Clopidogrel , Quimioterapia Combinada , Alemanha , Fidelidade a Diretrizes , Humanos , Inibidores da Agregação de Plaquetas/uso terapêutico , Cuidados Pós-Operatórios , Rivaroxabana/uso terapêutico , Prevenção Secundária , Ticlopidina/análogos & derivados , Ticlopidina/uso terapêutico , Veias/transplante
20.
Lancet ; 391(10137): 2325-2334, 2018 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-29900874

RESUMO

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS) increases the risk of cardiovascular events and deaths, which anticoagulation therapy could prevent. Dabigatran prevents perioperative venous thromboembolism, but whether this drug can prevent a broader range of vascular complications in patients with MINS is unknown. The MANAGE trial assessed the potential of dabigatran to prevent major vascular complications among such patients. METHODS: In this international, randomised, placebo-controlled trial, we recruited patients from 84 hospitals in 19 countries. Eligible patients were aged at least 45 years, had undergone non-cardiac surgery, and were within 35 days of MINS. Patients were randomly assigned (1:1) to receive dabigatran 110 mg orally twice daily or matched placebo for a maximum of 2 years or until termination of the trial and, using a partial 2-by-2 factorial design, patients not taking a proton-pump inhibitor were also randomly assigned (1:1) to omeprazole 20 mg once daily, for which results will be reported elsewhere, or matched placebo to measure its effect on major upper gastrointestinal complications. Research personnel randomised patients through a central 24 h computerised randomisation system using block randomisation, stratified by centre. Patients, health-care providers, data collectors, and outcome adjudicators were masked to treatment allocation. The primary efficacy outcome was the occurrence of a major vascular complication, a composite of vascular mortality and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism. The primary safety outcome was a composite of life-threatening, major, and critical organ bleeding. Analyses were done according to the intention-to-treat principle. This trial is registered with ClinicalTrials.gov, number NCT01661101. FINDINGS: Between Jan 10, 2013, and July 17, 2017, we randomly assigned 1754 patients to receive dabigatran (n=877) or placebo (n=877); 556 patients were also randomised in the omeprazole partial factorial component. Study drug was permanently discontinued in 401 (46%) of 877 patients allocated to dabigatran and 380 (43%) of 877 patients allocated to placebo. The composite primary efficacy outcome occurred in fewer patients randomised to dabigatran than placebo (97 [11%] of 877 patients assigned to dabigatran vs 133 [15%] of 877 patients assigned to placebo; hazard ratio [HR] 0·72, 95% CI 0·55-0·93; p=0·0115). The primary safety composite outcome occurred in 29 patients (3%) randomised to dabigatran and 31 patients (4%) randomised to placebo (HR 0·92, 95% CI 0·55-1·53; p=0·76). INTERPRETATION: Among patients who had MINS, dabigatran 110 mg twice daily lowered the risk of major vascular complications, with no significant increase in major bleeding. Patients with MINS have a poor prognosis; dabigatran 110 mg twice daily has the potential to help many of the 8 million adults globally who have MINS to reduce their risk of a major vascular complication [corrected]. FUNDING: Boehringer Ingelheim and Canadian Institutes of Health Research.


Assuntos
Dabigatrana/farmacologia , Hemorragia/complicações , Infarto do Miocárdio/tratamento farmacológico , Doença Arterial Periférica/complicações , Acidente Vascular Cerebral/complicações , Tromboembolia Venosa/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antitrombinas/farmacologia , Dabigatrana/administração & dosagem , Dabigatrana/efeitos adversos , Feminino , Hemorragia/tratamento farmacológico , Hemorragia/prevenção & controle , Humanos , Masculino , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/mortalidade , Omeprazol/administração & dosagem , Omeprazol/uso terapêutico , Período Perioperatório/mortalidade , Doença Arterial Periférica/tratamento farmacológico , Doença Arterial Periférica/prevenção & controle , Efeito Placebo , Inibidores da Bomba de Prótons/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/prevenção & controle , Trombose/patologia , Resultado do Tratamento , Troponina/efeitos dos fármacos , Troponina/metabolismo , Tromboembolia Venosa/prevenção & controle
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