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1.
BMC Nephrol ; 20(1): 437, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31775670

RESUMO

BACKGROUND: Despite improvement in short-term outcome of kidney transplants, the long-term survival of kidney transplants has not changed over past decades. Kidney biopsy is the gold standard of transplant pathology but it's invasive. Quantification of transplant blood flow could provide a novel non-invasive method to evaluate transplant pathology. The aim of this retrospective cross-sectional pilot study was to evaluate positron emission tomography (PET) as a method to measure kidney transplant perfusion and find out if there is correlation between transplant perfusion and histopathology. METHODS: Renal cortical perfusion of 19 kidney transplantation patients [average time from transplantation 33 (17-54) months; eGFR 55 (47-69) ml/min] and 10 healthy controls were studied by [15 O]H2O PET. Perfusion and Doppler resistance index (RI) of transplants were compared with histology of one-year protocol transplant biopsy. RESULTS: Renal cortical perfusion of healthy control subjects and transplant patients were 2.7 (2.4-4.0) ml min- 1 g- 1 and 2.2 (2.0-3.0) ml min- 1 g- 1, respectively (p = 0.1). Renal vascular resistance (RVR) of the patients was 47.0 (36.7-51.4) mmHg mL- 1min- 1g- 1 and that of the healthy 32.4 (24.6-39.6) mmHg mL- 1min-1g-1 (p = 0.01). There was a statistically significant correlation between Doppler RI and perfusion of transplants (r = - 0.51, p = 0.026). Transplant Doppler RI of the group of mild fibrotic changes [0.73 (0.70-0.76)] and the group of no fibrotic changes [0.66 (0.61-0.72)] differed statistically significantly (p = 0.03). No statistically significant correlation was found between cortical perfusion and fibrosis of transplants (p = 0.56). CONCLUSIONS: [15 O]H2O PET showed its capability as a method in measuring perfusion of kidney transplants. RVR of transplant patients with stage 2-3 chronic kidney disease was higher than that of the healthy, although kidney perfusion values didn't differ between the groups. Doppler based RI correlated with perfusion and fibrosis of transplants.

2.
Gastroenterology ; 157(3): 682-691, ago., 30 2019. ilus, tab
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1015771

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 x 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 (5mg 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. (AU)


Assuntos
Bactérias , Doenças Cardiovasculares , Aspirina
3.
Gastroenterology ; 157(2): 403-412, Aug., 2019. tabela, grafico
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1022748

RESUMO

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528).CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doenças Cardiovasculares/prevenção & controle , Aspirina/administração & dosagem , Método Duplo-Cego , Relação Dose-Resposta a Droga , Hemorragia Gastrointestinal/prevenção & controle , Anticoagulantes/administração & dosagem
4.
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
5.
Gastroenterology ; 157(2): 403-412.e5, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31054846

RESUMO

BACKGROUND & AIMS: Antiplatelets and anticoagulants are associated with increased upper gastrointestinal bleeding. We evaluated whether proton pump inhibitor therapy could reduce this risk. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease. Participants were randomly assigned to groups given pantoprazole 40 mg daily or placebo, as well as rivaroxaban 2.5 mg twice daily with aspirin 100 mg once daily, rivaroxaban 5 mg twice daily, or aspirin 100 mg alone. The primary outcome was time to first upper gastrointestinal event, defined as a composite of overt bleeding, upper gastrointestinal bleeding from a gastroduodenal lesion or of unknown origin, occult bleeding, symptomatic gastroduodenal ulcer or ≥5 erosions, upper gastrointestinal obstruction, or perforation. RESULTS: There was no significant difference in upper gastrointestinal events between the pantoprazole group (102 of 8791 events) and the placebo group (116 of 8807 events) (hazard ratio, 0.88; 95% confidence interval [CI], 0.67-1.15). Pantoprazole significantly reduced bleeding of gastroduodenal lesions (hazard ratio, 0.52; 95% confidence interval, 0.28-0.94; P = .03); this reduction was greater when we used a post-hoc definition of bleeding gastroduodenal lesion (hazard ratio, 0.45; 95% confidence interval, 0.27-0.74), although the number needed to treat still was high (n = 982; 95% confidence interval, 609-2528). CONCLUSIONS: In a randomized placebo-controlled trial, we found that routine use of proton pump inhibitors in patients receiving low-dose anticoagulation and/or aspirin for stable cardiovascular disease does not reduce upper gastrointestinal events, but may reduce bleeding from gastroduodenal lesions. ClinicalTrials.gov ID: NCT01776424.


Assuntos
Anticoagulantes/efeitos adversos , Doenças Cardiovasculares/prevenção & controle , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Úlcera Péptica/prevenção & controle , Inibidores da Bomba de Prótons/administração & dosagem , Administração Oral , Idoso , Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Hemorragia Gastrointestinal/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/epidemiologia , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Resultado do Tratamento
6.
J Am Coll Cardiol ; 73(18): 2243-2250, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31072566

RESUMO

BACKGROUND: Chronic kidney disease is associated with an increased risk of both bleeding and ischemic cardiovascular events. OBJECTIVE: The purpose of this study was to determine the balance of risks and benefits from the dual pathway antithrombotic regimen (rivaroxaban 2.5 mg twice daily [bd] plus aspirin, compared with aspirin) in vascular patients with or without moderate renal dysfunction. METHODS: This was a secondary analysis of the COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) trial involving 27,395 patients with chronic coronary or peripheral artery disease. RESULTS: In COMPASS, 21,111 patients had an estimated glomerular filtration rate (GFR) at baseline of ≥60 ml/min, 6,276 had a GRF of <60 ml/min. Both the primary efficacy outcome (cardiovascular death, myocardial infarction, or stroke) and major bleeding were more frequent in those with renal dysfunction, and the frequency of these outcome events was inversely related to GFR. However, the primary outcome was consistently reduced with rivaroxaban 2.5 mg bd plus aspirin, irrespective of GFR category (GFR ≥60 ml/min, 3.5% rivaroxaban plus aspirin, 4.5% aspirin alone, hazard ratio [HR]: 0.76, 95% confidence interval [CI]: 0.64 to 0.90; GFR <60 ml/min, 6.4% rivaroxaban plus aspirin, 8.4% aspirin alone, HR: 0.75; 95% CI: 0.60 to 0.94). Major bleeding was more frequent with rivaroxaban 2.5 mg plus aspirin versus aspirin alone in those with GFR ≥60 ml/min (2.9% rivaroxaban plus aspirin, 1.6% aspirin alone, HR: 1.81; 95% CI: 1.44 to 2.28) and similarly in those with GFR <60 ml/min (3.9% rivaroxaban plus aspirin, 2.7% aspirin alone, HR: 1.47, 95% CI: 1.05 to 2.07). CONCLUSIONS: The benefits of the dual pathway COMPASS regimen (rivaroxaban 2.5 mg bd plus aspirin), versus aspirin alone, are preserved in patients with moderate renal dysfunction without evidence of an excess hazard of bleeding.

7.
EJNMMI Res ; 8(1): 45, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29892792

RESUMO

BACKGROUND: Microvascular function plays an important role in ARVD (atherosclerotic renovascular disease). RFR (renal flow reserve), the capacity of renal vasculature to dilate, is known to reflect renal microvascular function. In this pilot study, we assessed PET (positron emission tomography)-based RFR values of healthy persons and renal artery stenosis patients. Seventeen patients with ARVD and eight healthy subjects were included in the study. Intravenous enalapril 1 mg was used as a vasodilatant, and the maximum response (blood pressure and RFR) to it was measured at 40 min. Renal perfusion was measured by means of oxygen-15-labeled water PET. RFR was calculated as a difference of stress flow and basal flow and was expressed as percent [(stress blood flow - basal blood flow)/basal blood flow] × 100%. RESULTS: RFR of the healthy was 22%. RFR of the stenosed kidneys of bilateral stenosis patients (27%) was higher than that of the stenosed kidneys of unilateral stenosis patients (15%). RFR of the contralateral kidneys of unilateral stenosis patients was 21%. There was no difference of statistical significance between RFR values of ARVD subgroups or between ARVD subgroups and the healthy. In the stenosed kidneys of unilateral ARVD patients, stenosis grade of the renal artery correlated negatively with basal (p = 0.04) and stress flow (p = 0.02). Dispersion of RFR values was high. CONCLUSIONS: This study is the first to report [15O]H2O PET-based RFR values of healthy subjects and ARVD patients in humans. The difference between RFR values of ARVD patients and the healthy did not reach statistical significance perhaps because of high dispersion of RFR values. [15O]H2O PET is a valuable non-invasive and quantitative method to evaluate renal blood flow though high dispersion makes imaging challenging. Larger studies are needed to get more information about [15O]H2O PET method in evaluation of renal blood flow.

8.
Lancet ; 391(10117): 205-218, 2018 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-29132879

RESUMO

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants. FINDINGS: Between March 12, 2013, and May 10, 2016, 27 395 patients were enrolled to the COMPASS trial, of whom 24 824 patients had stable coronary artery disease from 558 centres. The combination of rivaroxaban plus aspirin reduced the primary outcome more than aspirin alone (347 [4%] of 8313 vs 460 [6%] of 8261; hazard ratio [HR] 0·74, 95% CI 0·65-0·86, p<0·0001). By comparison, treatment with rivaroxaban alone did not significantly improve the primary outcome when compared with treatment with aspirin alone (411 [5%] of 8250 vs 460 [6%] of 8261; HR 0·89, 95% CI 0·78-1·02, p=0·094). Combined rivaroxaban plus aspirin treatment resulted in more major bleeds than treatment with aspirin alone (263 [3%] of 8313 vs 158 [2%] of 8261; HR 1·66, 95% CI 1·37-2·03, p<0·0001), and similarly, more bleeds were seen in the rivaroxaban alone group than in the aspirin alone group (236 [3%] of 8250 vs 158 [2%] of 8261; HR 1·51, 95% CI 1·23-1·84, p<0·0001). The most common site of major bleeding was gastrointestinal, occurring in 130 [2%] patients who received combined rivaroxaban plus aspirin, in 84 [1%] patients who received rivaroxaban alone, and in 61 [1%] patients who received aspirin alone. Rivaroxaban plus aspirin reduced mortality when compared with aspirin alone (262 [3%] of 8313 vs 339 [4%] of 8261; HR 0·77, 95% CI 0·65-0·90, p=0·0012). INTERPRETATION: In patients with stable coronary artery disease, addition of rivaroxaban to aspirin lowered major vascular events, but increased major bleeding. There was no significant increase in intracranial bleeding or other critical organ bleeding. There was also a significant net benefit in favour of rivaroxaban plus aspirin and deaths were reduced by 23%. Thus, addition of rivaroxaban to aspirin has the potential to substantially reduce morbidity and mortality from coronary artery disease worldwide. FUNDING: Bayer AG.


Assuntos
Aspirina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Doença da Artéria Coronariana/epidemiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Morbidade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Agregação de Plaquetas/efeitos adversos , Rivaroxabana/administração & dosagem , Rivaroxabana/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
9.
Lancet ; 391(10117): 205-218, 2018.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-36688

RESUMO

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality worldwide, and is a consequence of acute thrombotic events involving activation of platelets and coagulation proteins. Factor Xa inhibitors and aspirin each reduce thrombotic events but have not yet been tested in combination or against each other in patients with stable coronary artery disease. METHODS: In this multicentre, double-blind, randomised, placebo-controlled, outpatient trial, patients with stable coronary artery disease or peripheral artery disease were recruited at 602 hospitals, clinics, or community centres in 33 countries. This paper reports on patients with coronary artery disease. Eligible patients with coronary artery disease had to have had a myocardial infarction in the past 20 years, multi-vessel coronary artery disease, history of stable or unstable angina, previous multi-vessel percutaneous coronary intervention, or previous multi-vessel coronary artery bypass graft surgery. After a 30-day run in period, patients were randomly assigned (1:1:1) to receive rivaroxaban (2·5 mg orally twice a day) plus aspirin (100 mg once a day), rivaroxaban alone (5 mg orally twice a day), or aspirin alone (100 mg orally once a day). Randomisation was computer generated. Each treatment group was double dummy, and the patients, investigators, and central study staff were masked to treatment allocation. The primary outcome of the COMPASS trial was the occurrence of myocardial infarction, stroke, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants...(AU)


Assuntos
Rivaroxabana , Aspirina , Doença da Artéria Coronariana , Estudos de Casos e Controles
10.
N Engl J Med ; 377(14): 1319-1330, 2017 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-28844192

RESUMO

BACKGROUND: We evaluated whether rivaroxaban alone or in combination with aspirin would be more effective than aspirin alone for secondary cardiovascular prevention. METHODS: In this double-blind trial, we randomly assigned 27,395 participants with stable atherosclerotic vascular disease to receive rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction. The study was stopped for superiority of the rivaroxaban-plus-aspirin group after a mean follow-up of 23 months. RESULTS: The primary outcome occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=-4.126), but major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between these two groups. There were 313 deaths (3.4%) in the rivaroxaban-plus-aspirin group as compared with 378 (4.1%) in the aspirin-alone group (hazard ratio, 0.82; 95% CI, 0.71 to 0.96; P=0.01; threshold P value for significance, 0.0025). The primary outcome did not occur in significantly fewer patients in the rivaroxaban-alone group than in the aspirin-alone group, but major bleeding events occurred in more patients in the rivaroxaban-alone group. CONCLUSIONS: Among patients with stable atherosclerotic vascular disease, those assigned to rivaroxaban (2.5 mg twice daily) plus aspirin had better cardiovascular outcomes and more major bleeding events than those assigned to aspirin alone. Rivaroxaban (5 mg twice daily) alone did not result in better cardiovascular outcomes than aspirin alone and resulted in more major bleeding events. (Funded by Bayer; COMPASS ClinicalTrials.gov number, NCT01776424 .).


Assuntos
Aspirina/uso terapêutico , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Inibidores da Agregação de Plaquetas/uso terapêutico , Rivaroxabana/uso terapêutico , Idoso , Aspirina/efeitos adversos , Aterosclerose/complicações , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Método Duplo-Cego , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/efeitos adversos , Rivaroxabana/efeitos adversos , Prevenção Secundária/métodos
11.
Blood Press ; 26(2): 67-73, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27310566

RESUMO

Risk of cardiovascular events within the diabetic population has decreased and survival increased with patients living longer and thus facing the development of end-stage renal disease (ESRD). This calls for good care of patient with diabetes with a focus on hypertension. Patient data were collected from 42 Finnish primary care centres. Each was asked to enrol 10-12 consecutive patients with type-2 diabetes between March 2011 and August 2012. Along with the office blood pressure measurements and laboratory tests, the presence of albuminuria was measured and glomerular filtration rate estimated (eGFR). The 2013 ESH criteria for diabetic hypertensive patients (<140/85 mmHg) was reached by 39% of all 625 study patients and 38% of the pharmacologically treated 520 patients. The absence of detectable albumin in urine was significantly associated with the control of systolic blood pressure and achievement of treatment goals. Beta blockers were the most common antihypertensive agents and patients treated with them had lower eGFR compared to those not treated with these agents. The blood pressure of patients was not in full concordance with the present guideline recommendations. However, satisfactory improvement in blood pressure control, reduction of albuminuria and hence ESRD prevention was achieved.


Assuntos
Albuminúria , Pressão Sanguínea , Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Atenção Primária à Saúde , Adulto , Albuminúria/etiologia , Albuminúria/fisiopatologia , Albuminúria/terapia , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/terapia , Feminino , Finlândia , Humanos , Masculino , Pessoa de Meia-Idade
12.
Hemodial Int ; 21(4): 519-523, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-27866393

RESUMO

INTRODUCTION: Repetitive dialysis-induced cardiac injury is associated with elevated troponin levels, inflammation, and longitudinal reduction in cardiac function. Pathogenic autoantibodies to cardiac troponins (cTnAAb) produce inflammatory cardiomyopathy in murine models. This study aimed to explore the possibility that analogous autoimmune processes might occur in hemodialysis (HD) patients, by initially investigating cTnAAb prevalence, and exploring potential links with HD-induced myocardial stunning. METHODS: In 130 prevalent HD patients from two centers (Derby, UK; Turku, Finland), cTnAAb (immunoassay) and cardiac troponins were quantified. Sixty-four patients underwent serial echocardiography to assess myocardial stunning. FINDINGS: cTnAAb were present in 7% of patients. Dual positivity to cTnAAb and elevated cTn occurred in 3% and 6% for cTnI and cTnT, respectively. Patients with cTnAAb had significantly longer dialysis vintage (82 vs. 30 months, P = 0.024), higher cTnT (0.1 vs. 0.05 pg/mL, P = 0.04), cTnI (0.02 vs. 0.01 pg/mL, P = 0.029), and free PAPP-A (6.4 vs. 3.3 mIU/L, P = 0.038). DISCUSSION: This is the first description of cTnAAb in HD patients, which raises the possibility that longitudinal exposure to repetitive HD-induced cardiac injury may lead to further autoimmune-based myocardial insult.


Assuntos
Autoanticorpos/efeitos adversos , Diálise Renal/efeitos adversos , Troponina I/metabolismo , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/métodos
13.
Can J Cardiol ; 33(8): 1027-1035, 2017.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: ses-36563

RESUMO

BACKGROUND: Long-term aspirin prevents vascular events but is only modestly effective. Rivaroxaban alone or in combination with aspirin might be more effective than aspirin alone for vascular prevention in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD). Rivaroxaban as well as aspirin increase upper gastrointestinal (GI) bleeding and this might be prevented by proton pump inhibitor therapy. METHODS: Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) is a double-blind superiority trial comparing rivaroxaban 2.5 mg twice daily combined with aspirin 100 mg once daily or rivaroxaban 5 mg twice daily vs aspirin 100 mg once daily for prevention of myocardial infarction, stroke, or cardiovascular death in patients with stable CAD or PAD. Patients not taking a proton pump inhibitor were also randomized, using a partial factorial design, to pantoprazole 40 mg once daily or placebo. The trial was designed to have at least 90% power to detect a 20% reduction in each of the rivaroxaban treatment arms compared with aspirin and to detect a 50% reduction in upper GI complications with pantoprazole compared with placebo...(AU)


Assuntos
Cardiopatias , Anticoagulantes , Aspirina
14.
Nephron ; 129(3): 171-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25766334

RESUMO

BACKGROUND/AIMS: Pregnancy-associated plasma protein-A (PAPP-A) is a putative marker of atheroma instability and ischaemic myocardial stress prior to necrosis. Total PAPP-A (tPAPP-A) levels in acute coronary syndromes predict adverse outcomes. However, free PAPP-A (fPAPP-A) predominates in the circulation. Ischaemic haemodialysis (HD)-induced cardiac injury (myocardial stunning) is common and is associated with markers of myocardial necrosis, inflammation, cardiovascular events and mortality. Coronary plaque instability in pathophysiology of HD-induced myocardial stunning has not been studied. We aimed to investigate the relationship of fPAPP-A with stunning and mortality. METHODS: 130 prevalent patients from two HD centres (Finland and UK) were studied. Pre-HD free, complexed and total PAPP-A were measured by immunoassay. A subset of 62 patients underwent echocardiography to assess HD-induced myocardial stunning. The mean duration of follow-up was 407 ± 98 days. RESULTS: fPAPP-A was elevated (median: 3.45 mIU/l) and correlated with dialysis vintage (r = 0.391, p < 0.001), cardiac troponin T (cTnT; r = 0.29, p = 0.001) and cardiac troponin I (cTnI; r = 0.22, p = 0.01). PAPP-A was not related to stunning. Dialysis vintage and cTnT independently predicted Ln fPAPP-A (model R = 0.463). fPAPP-A, cTnT and age independently predicted death (Nagelkerke R(2) = 0.362). CONCLUSIONS: fPAPP-A, a novel predictor of HD-related mortality, demonstrates better prognostic power than tPAPP-A. Coronary plaque instability may contribute to sub-lethal myocardial injury, but may not be critical in pathogenesis of HD-induced ischaemic cardiac injury.


Assuntos
Isquemia Miocárdica/etiologia , Proteína Plasmática A Associada à Gravidez/metabolismo , Diálise Renal/efeitos adversos , Diálise Renal/mortalidade , Idoso , Biomarcadores , Estudos de Coortes , Feminino , Finlândia/epidemiologia , Seguimentos , Testes de Função Cardíaca , Humanos , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Miocárdio Atordoado/etiologia , Miocárdio Atordoado/fisiopatologia , Valor Preditivo dos Testes , Gravidez , Proteína Plasmática A Associada à Gravidez/análise , Troponina C/sangue , Ultrassonografia
15.
Prim Care Diabetes ; 9(1): 31-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25066820

RESUMO

OBJECTIVE: To examine the prevalence of chronic kidney disease (CKD) and related cardiovascular morbidity in a cross-sectional population in patients with type 2 diabetes (T2D) treated in a primary care setting in Finland. RESEARCH DESIGN AND METHODS: Data were collected and recorded from 42 primary care centres, which recruited 629 patients diagnosed with type 2 diabetes (T2D) to this non-interventional study. Data including patient characteristics, kidney function and albuminuria, blood pressure, HbA1c, lipid and lipoprotein levels, and diabetes duration as well as current medication was collected in each patient. RESULTS: In the final study population of 625 patients, the mean age was 67 years (range 29-92 years), BMI 32.8 kg/m(2) (95% CI 32-33), blood pressure 142/80 mmHg (140-143/80-81) and HbA1c 7.1% (7.0-7.2) (53.8 mmol/mol, 53-55) and the median duration of diabetes was 9.2 years ranging from newly diagnosed to 43 years. History of dyslipidemia had in 73.3% of patients, 27.8% had cardiovascular disease and 82.7% had hypertension. The primary endpoint, prevalence of CKD of any grade (1-5) or albuminuria, was 68.6%. Regarding declined renal function, 16.2% of patients had an estimated glomerular filtration rate (eGFR) <60 ml/min/1.72 m(2), classifying as CKD 3-5. Only one patient was within CKD5. Regarding renal damage, albuminuria was present in 24.3% of patients, with microalbuminuria in 17.1% and macroalbuminuria in 7.2%, respectively. Combining the patients with CKD 3-5 and/or the presence of albuminuria, 34.7% seemed to suffer from significant CKD. The proportion of patients with albuminuria increased with a decrease in glomerular filtration rate. Historically, diabetic nephropathy had been diagnosed in 24.3% of the patients. CONCLUSIONS: Nearly 70% of patients with T2D treated in primary care in Finland have some sign of CKD and nearly half of all T2D patients have a significant CKD. However, only half of the latter had it diagnosed and documented in their patient charts, thus highlighting the importance of performing routine screening of nephropathy by measuring both albuminuria and eGFR in patients with T2D. Prevention of this complication with active therapy for risk factors, such as hypertension and dyslipidemia is warranted.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/epidemiologia , Hipoglicemiantes/uso terapêutico , Atenção Primária à Saúde , Insuficiência Renal Crônica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminúria/diagnóstico , Albuminúria/epidemiologia , Comorbidade , Estudos Transversais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Feminino , Finlândia/epidemiologia , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prevalência , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Índice de Gravidade de Doença , Fatores de Tempo
16.
Case Rep Nephrol Urol ; 4(1): 82-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24847350

RESUMO

Thromboembolic occlusion is a rare cause of acute kidney injury (AKI). It may lead to permanent loss of renal function. Our patient, who had dilated cardiomyopathy and prosthetic aortic valve, presented with AKI due to thromboembolic arterial occlusion of a solitary functioning kidney. After 2 weeks delay, local intra-arterial thrombolytic treatment with recombinant tissue plasminogen activator was performed without sufficient effect. However, a subsequent percutaneous transluminal angioplasty with stenting was successful. Diuresis began immediately, and renal function was fully recovered after 2 weeks. Although there had been no evident arterial circulation in the kidney, we think that minor flow through subtotal occlusion of the main renal artery made the hibernation of kidney tissue possible and contributed to the recovery. Thus, even after prolonged ischemia, revascularization can be useful.

17.
Nephrol Dial Transplant ; 27(10): 3843-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22785108

RESUMO

BACKGROUND: Only a small fraction of patients with atherosclerotic renovascular disease (ARVD) treated with revascularization have improved renal function after the procedure. It has been suggested that this may be due to effects of renal microvascular disease. Our aim was to measure the effect of renal artery stenosis (RAS) revascularization on renal perfusion in patients with renovascular disease. METHODS: Seventeen renovascular disease patients were treated by dilatation of unilateral (N = 8) or bilateral (N = 9) RAS (N = 23 kidneys), mainly because of uncontrolled or refractory hypertension. The patients were studied before and after (103 ± 29 days) the procedure. Renal perfusion was measured using quantitative positron emission tomography (PET) perfusion imaging. RESULTS: Although renal perfusion correlated inversely with the degree of RAS in patients with renovascular disease, it did not change after revascularization. CONCLUSIONS: Our data support the notion of former clinical trials that angiographic severity of RAS does not determine the response to revascularization. Quantitative PET perfusion imaging is a promising tool to noninvasively measure renal perfusion for the assessment of physiological impact of RAS.


Assuntos
Angioplastia/métodos , Aterosclerose/cirurgia , Hipertensão Renovascular/cirurgia , Obstrução da Artéria Renal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/diagnóstico por imagem , Aterosclerose/fisiopatologia , Feminino , Humanos , Hipertensão Renovascular/diagnóstico por imagem , Hipertensão Renovascular/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Obstrução da Artéria Renal/diagnóstico por imagem , Obstrução da Artéria Renal/fisiopatologia , Circulação Renal
18.
Duodecim ; 127(16): 1690-6, 2011.
Artigo em Finlandês | MEDLINE | ID: mdl-21972587

RESUMO

Calciphylaxis is a rare disease primarily affecting patients dependent on dialysis. It is characterised by small vessel media calcification leading to cutaneous ischemia and necrosis. The mortality rate is high with infection and sepsis being the most common causes of death. Calcium salts, vitamin D and high levels of serum calcium and phosphorus increase the risk of calciphylaxis. Current therapies including restoration of mineral homeostasis, wound care and pain control, are not entirely effective. Sodium thiosulfate, by dissolving calcium deposits, is a novel therapeutic choice for calciphylaxis. It has proved successful also in cases refractory to conventional treatment.


Assuntos
Calciofilaxia/tratamento farmacológico , Calciofilaxia/etiologia , Quelantes/uso terapêutico , Diálise Renal/efeitos adversos , Tiossulfatos/uso terapêutico , Calciofilaxia/mortalidade , Humanos
19.
Duodecim ; 125(20): 2236-7, 2009.
Artigo em Finlandês | MEDLINE | ID: mdl-19998761

RESUMO

Acute kidney injury (AKI) is associated with significant morbidity and mortality. Its prevalence is increasing. Risk factors are older age, diabetes, atherosclerosis, medications, heart failure, male sex, and even mild chronic renal failure. Early detection of AKI is essential, as is the prevention of AKI related to hypovolaemia, contrast agents and nephrotoxic medications. No medication is available for developed AKI, the only therapeutic option being renal replacement therapy. Thus, prevention by adequate fluid therapy, optimisation of renal perfusion pressure and exclusion of post-renal causes of AKI are crucial. To date, the long-term outcome in AKI is unsatisfactory and the costs are high.


Assuntos
Lesão Renal Aguda/terapia , Lesão Renal Aguda/diagnóstico , Adulto , Humanos , Diálise Renal , Fatores de Risco
20.
Nephrol Dial Transplant ; 24(9): 2773-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19369689

RESUMO

BACKGROUND: Even minor renal dysfunction is a powerful cardiovascular risk factor. The abnormalities in coronary and peripheral artery function in different stages of chronic kidney disease (CKD) remain poorly understood. Our aim was to test by a positron emission tomography (PET)-based method whether microvascular dysfunction, an early marker of coronary dysfunction, exists already in early stages of CKD. METHODS: Myocardial blood flow was measured at baseline and during dipyridamole-induced hyperaemia by PET. Peripheral artery endothelial function was examined by measuring flow-mediated dilatation (FMD) of the brachial artery at rest and during reactive hyperaemia. Twenty-two patients with moderate to severe kidney failure and 10 healthy controls were investigated. Diabetic patients were excluded. Baseline characteristics were similar between the groups with the exception of antihypertensive medication in all CKD patients. RESULTS: The basal myocardial perfusion was statistically significantly higher in CKD patients than observed values in similarly aged controls. There was a statistically significant negative correlation between the baseline myocardial perfusion and the estimated glomerular filtration rate. Coronary flow reserve was comparable to healthy controls in all patients. FMD was significantly reduced in all patients with CKD regardless of the stage of kidney failure. CONCLUSIONS: Coronary flow reserve was normal although baseline myocardial blood flow was increased in all CKD patients as compared to healthy controls. Peripheral endothelial dysfunction was detected in all patients. Our findings suggest that coronary perfusion and peripheral vascular function are disturbed by different mechanisms in patients with CKD.


Assuntos
Circulação Coronária , Coração/diagnóstico por imagem , Insuficiência Renal Crônica/fisiopatologia , Adulto , Idoso , Estudos de Casos e Controles , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Circulação Coronária/fisiologia , Endotélio Vascular/fisiopatologia , Feminino , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico por imagem , Falência Renal Crônica/fisiopatologia , Masculino , Microcirculação/fisiologia , Pessoa de Meia-Idade , Imagem de Perfusão do Miocárdio , Tomografia por Emissão de Pósitrons , Fluxo Sanguíneo Regional/fisiologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico por imagem , Fatores de Risco , Resistência Vascular/fisiologia
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