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2.
Scand J Prim Health Care ; 42(2): 347-354, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38456742

RESUMO

OBJECTIVE: A pilot study to evaluate a staff training intervention implementing a nurse-led hypertension care model. DESIGN AND SETTING: Clinical and laboratory data from all primary care centres (PCCs) in the Swedish region Västra Götaland (VGR), retrieved from regional registers. Intervention started 2018 in 11 PCCs. A total of 190 PCCs served as controls. Change from baseline was assessed 2 years after start of intervention. INTERVENTION: Training of selected personnel, primarily in drug choice, team-based care, measurement techniques, and use of standardized medical treatment protocols. PATIENTS: Hypertensive patients without diabetes or ischemic heart disease were included. The intervention and control groups contained approximately 10,000 and 145,000 individuals, respectively. MAIN OUTCOME MEASURES: Blood pressure (BP) <140/90 mmHg, LDL-cholesterol (LDL-C) <3.0 mmol/L, BP ending on -0 mmHg (digit preference, an indirect sign of manual measuring technique), choice of antihypertensive drugs, cholesterol lowering therapy and attendance patterns were measured. RESULTS: In the intervention group, the percentage of patients reaching the BP target did not change significantly, 56%-61% (control 50%-52%), non-significant. However, the percentage of patients with LDL-C < 3.0 mmol/L increased from 34%-40% (control 36%-36%), p = .043, and digit preference decreased, 39%-27% (control 41%-35%), p = 0.000. The number of antihypertensive drugs was constant, 1.63 - 1.64 (control 1.62 - 1.62), non-significant, but drug choice changed in line with recommendations. CONCLUSION: Although this primary care intervention based on staff training failed to improve BP control, it resulted in improved cardiovascular control by improved cholesterol lowering treatment.


Hypertension is common and often suboptimally treated in relation to existing guidelines.This register study evaluates the results of a staff training intervention promoting nurse-led care.The intervention had an impact on measurement techniques, drug choice and improved cholesterol control.


Assuntos
Anti-Hipertensivos , Hipertensão , Humanos , Anti-Hipertensivos/uso terapêutico , LDL-Colesterol/farmacologia , LDL-Colesterol/uso terapêutico , Projetos Piloto , Hipertensão/epidemiologia , Pressão Sanguínea/fisiologia , Colesterol , Atenção Primária à Saúde
3.
J Am Heart Assoc ; 11(10): e024703, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35574947

RESUMO

Background The CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74 years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long-term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new-onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA2DS2-VASc scoring system for estimating the 1-year ischemic stroke risk in patients with new-onset postoperative atrial fibrillation after coronary artery bypass grafting. Methods and Results All patients with new-onset postoperative atrial fibrillation and without oral anticoagulation after first-time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry-based observational cohort study. The 1-year ischemic stroke rate at each step of the CHA2DS2-VASc score was estimated using a Kaplan-Meier estimator. Of the 6368 patients included (mean age, 69.9 years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow-up. The ischemic stroke rate at 1 year was 0.3%, 0.7%, and 1.5% in patients with CHA2DS2-VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results. Conclusions Patients with new-onset atrial fibrillation after coronary artery bypass grafting and a CHA2DS2-VASc score <3 have such a low 1-year risk for ischemic stroke that oral anticoagulation therapy should probably be avoided.


Assuntos
Fibrilação Atrial , Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Ponte de Artéria Coronária/efeitos adversos , Feminino , Humanos , Masculino , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle
4.
Eur J Prev Cardiol ; 29(1): 158-166, 2022 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-34056646

RESUMO

AIMS: To describe 8-year trends in blood pressure (BP) control, blood lipid control, and smoking habits in patients with hypertension from QregPV, a primary care register in the Region of Västra Götaland, Sweden. METHODS AND RESULTS: QregPV features clinical data on BP, low-density lipoprotein cholesterol (LDL-C), and smoking habits in 392 277 patients with hypertension or coronary heart disease or diabetes mellitus or any combination of the three diagnoses. Data from routine clinical practice have been automatically reported on a monthly basis to QregPV from all primary care centres in Västra Götaland (population 1.67 million) since 2010. Additional data on diagnoses, dispensed drugs and socioeconomic factors were acquired through linkage to regional and national registers. We identified 259 753 patients with hypertension, but without coronary heart disease and diabetes mellitus, in QregPV. From 2010 to 2017, the proportion of patients with BP <140/90 mmHg increased from 38.9% to 49.1%, while the proportion of patients with LDL-C <2.6 mmol/L increased from 19.7% to 21.1% and smoking decreased from 15.7% to 12.3%. However, in 2017, only 10.0% of all patients with hypertension had attained target levels of BP <140/90 mmHg, LDL-C < 2.6 mmol/L while being also non-smokers. The remaining 90.0% were still exposed to at least one uncontrolled, modifiable risk factor for cardiovascular disease. CONCLUSIONS: These regionwide data from eight consecutive years in 259 753 patients with hypertension demonstrate a large potential for risk factor improvement. An increased use of statins and antihypertensive drugs should, in addition to lifestyle modifications, decrease the risk of cardiovascular disease in these patients.


Assuntos
Hipertensão , Pressão Sanguínea/fisiologia , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Lipídeos , Atenção Primária à Saúde , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Suécia/epidemiologia
5.
Clin Epidemiol ; 13: 649-659, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34354377

RESUMO

BACKGROUND: In response to the Covid-19 pandemic, we designed and initiated a nationwide linked multi-register, regularly updated, observational study for timely response to urgent scientific questions. AIM: To describe the SCIFI-PEARL (Swedish Covid-19 Investigation for Future Insights - a Population Epidemiology Approach using Register Linkage) linked database encompassing essentially all known diagnosed Swedish Covid-19 patients plus a large general population comparison cohort and outline its utility in the current and future phases of the pandemic. METHODS: Individuals with Covid-19 from the entire country are identified on a regularly updated basis, from different sources: all individuals from SmiNet, the national database of notifiable diseases, with positive SARS-CoV-2 polymerase chain reaction (PCR) test results; patients identified in the healthcare system by condition (ICD-10) or procedure codes in the National Patient Register or Cause-of-Death Register; patients identified through several disease-specific national quality registers (NQRs); and in two regions additionally patients identified in primary care. A comparison population was obtained by stratified random sampling from Swedish national population registers. Data from all these registers plus the National Prescribed Drug Register, the Cancer Register, national sociodemographic registers, some additional NQRs, the National Vaccination Register, and further data sources, are then linked to all study subjects (Covid-19 cases and population cohort). New cases in the study population and all data for all subjects are updated every few months, as required. CONCLUSION AND UTILITY: The SCIFI-PEARL study cohort captures Swedish residents with Covid-19 on an ongoing basis, includes a representative general population comparison cohort, and links to a broad range of national and regional healthcare data for a comprehensive longitudinal view of the Covid-19 pandemic. By combining high-quality national registers with short time delay and continuous repeated linkage and updating, the project brings timely and internationally relevant data for epidemiological research on SARS-CoV-2. Our efforts provide an example and important learnings for similar efforts internationally in the future.

6.
J Am Heart Assoc ; 10(1): e017966, 2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33251914

RESUMO

Background The long-term impact of new-onset postoperative atrial fibrillation (POAF) after coronary artery bypass grafting and the benefit of early-initiated oral anticoagulation (OAC) in patients with POAF are uncertain. Methods and Results All patients who underwent coronary artery bypass grafting without preoperative atrial fibrillation in Sweden from 2007 to 2015 were included in a population-based study using data from 4 national registries: SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies), National Patient Registry, Dispensed Drug Registry, and Cause of Death Registry. POAF was defined as any new-onset atrial fibrillation during the first 30 postoperative days. Cox regression models (adjusted for age, sex, comorbidity, and medication) were used to assess long-term outcome in patients with and without POAF, and potential associations between early-initiated OAC and outcome. In a cohort of 24 523 patients with coronary artery bypass grafting, POAF occurred in 7368 patients (30.0%), and 1770 (24.0%) of them were prescribed OAC within 30 days after surgery. During follow-up (median 4.5 years, range 0‒9 years), POAF was associated with increased risk of ischemic stroke (adjusted hazard ratio [aHR] 1.18 [95% CI, 1.05‒1.32]), any thromboembolism (ischemic stroke, transient ischemic attack, or peripheral arterial embolism) (aHR 1.16, 1.05‒1.28), heart failure hospitalization (aHR 1.35, 1.21‒1.51), and recurrent atrial fibrillation (aHR 4.16, 3.76‒4.60), but not with all-cause mortality (aHR 1.08, 0.98‒1.18). Early initiation of OAC was not associated with reduced risk of ischemic stroke or any thromboembolism but with increased risk for major bleeding (aHR 1.40, 1.08‒1.82). Conclusions POAF after coronary artery bypass grafting is associated with negative prognostic impact. The role of early OAC therapy remains unclear. Studies aiming at reducing the occurrence of POAF and its consequences are warranted.


Assuntos
Aspirina/administração & dosagem , Fibrilação Atrial , Ponte de Artéria Coronária/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Complicações Pós-Operatórias , Tromboembolia , Varfarina/administração & dosagem , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Ponte de Artéria Coronária/métodos , Doença da Artéria Coronariana/cirurgia , Inibidores do Fator Xa/classificação , Feminino , Humanos , Efeitos Adversos de Longa Duração/diagnóstico , Efeitos Adversos de Longa Duração/tratamento farmacológico , Efeitos Adversos de Longa Duração/epidemiologia , Masculino , Avaliação de Resultados em Cuidados de Saúde , Inibidores da Agregação Plaquetária/administração & dosagem , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Suécia/epidemiologia , Tromboembolia/etiologia , Tromboembolia/mortalidade , Tromboembolia/prevenção & controle , Tempo para o Tratamento
7.
BMJ Open ; 10(10): e036920, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-33039993

RESUMO

OBJECTIVES: The protective effect of lipid-lowering treatment for secondary prevention after coronary heart disease (CHD) has been well documented. Current guidelines recommend a target level for low-density lipoprotein cholesterol (LDL-C) of ≤1.8 mmol/L. The aim was to describe lipid-lowering treatment patterns and to provide an estimate of the potential reductions in cardiovascular disease (CVD) events with improved adherence to guidelines. DESIGN: Cross-sectional. SETTING: Primary care in a large Swedish region. PARTICIPANTS: 37 120 patients with CHD in a Swedish regional primary care quality register (QregPV), by 31 December 2015. PRIMARY AND SECONDARY OUTCOME MEASURES: Proportion of patients on statin treatment and proportion of patients achieving LDL-C ≤1.8 mmol/L. Estimated number of CVD events calculated for (1) current treatment, (2) improved treatment and (3) lowered LDL-C, based on applying rate reductions from meta-analyses of randomised trials to the potentially undertreated population. Risk estimation modelling was based on 52 042 patients in the same register on January 2011 followed for 5 years. RESULTS: Of 37 120 patients, 18% reached LDL-C ≤1.8 mmol/L and 32% were not on statin treatment. Based on individual risks, the estimated number of CVD events in the study group over 5 years was 9209/37 120. If all patients without a statin or with less potent statin treatment were given atorvastatin 80 mg, an estimated reduction of CVD events by 14% (7901 vs 9209) was seen. If all patients achieved LDL-C ≤1.8 mmol/L, the number of events was estimated to be reduced by 18% (7577 vs 9209). CONCLUSION: One-third of patients with CHD in primary care were not on lipid-lowering treatment. Based on the assumption that included patients would react to statin therapy the same way as the patients in randomised trials, improved adherence to treatment guidelines could lead to a substantial reduction in new CVD events.


Assuntos
Doenças Cardiovasculares , Inibidores de Hidroximetilglutaril-CoA Redutases , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Estudos Transversais , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos , Atenção Primária à Saúde , Prevenção Secundária , Suécia/epidemiologia , Resultado do Tratamento
8.
Diabetes Care ; 43(6): 1276-1284, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32152136

RESUMO

OBJECTIVE: We examined detailed renal and cardiovascular (CV) outcomes after gastric bypass (GBP) surgery in people with obesity and type 2 diabetes mellitus (T2DM), across several renal function categories, in a nationwide cohort study. RESEARCH DESIGN AND METHODS: We linked data from the National Diabetes Register and the Scandinavian Obesity Surgery Register with four national databases holding information on socioeconomic variables, medications, hospitalizations, and causes of death and matched 5,321 individuals with T2DM who had undergone GBP with 5,321 who had not (age 18-65 years, mean BMI >40 kg/m2, mean follow-up >4.5 years). The risks of postoperative outcomes were assessed with Cox regression models. RESULTS: During the first years postsurgery, there were small reductions in creatinine and albuminuria and stable estimated glomerular filtration rate (eGFR) in the GBP group. The incidence rates of most outcomes relating to renal function, CV disease, and mortality were lower after GBP, being particularly marked for heart failure (hazard ratio [HR] 0.33 [95% CI 0.24, 0.46]) and CV mortality (HR 0.36 [(95% CI 0.22, 0.58]). The risk of a composite of severe renal disease or halved eGFR was 0.56 (95% CI 0.44, 0.71), whereas nonfatal CV risk was lowered less (HR 0.82 [95% CI 0.70, 0.97]) after GBP. Risks for key outcomes were generally lower after GBP in all eGFR strata, including in individuals with eGFR <30 mL/min/1.73 m2. CONCLUSIONS: Our data suggest robust benefits for renal outcomes, heart failure, and CV mortality after GBP in individuals with obesity and T2DM. These results suggest that marked weight loss yields important benefits, particularly on the cardiorenal axis (including slowing progression to end-stage renal disease), whatever the baseline renal function status.


Assuntos
Sistema Cardiovascular/fisiopatologia , Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica , Rim/fisiopatologia , Obesidade/cirurgia , Redução de Peso/fisiologia , Adolescente , Adulto , Idoso , Aterosclerose/epidemiologia , Aterosclerose/etiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/epidemiologia , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/fisiopatologia , Medição de Risco , Comportamento de Redução do Risco , Suécia/epidemiologia , Resultado do Tratamento , Adulto Jovem
9.
J Hypertens ; 37(11): 2269-2279, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31188164

RESUMO

OBJECTIVE: The aim of this study was to compare the risk of cardiovascular disease (CVD) - nonfatal acute myocardial infarction (AMI) or stroke - at blood pressure levels that meet current recommendations with risk at lower levels, particularly in older patients. METHODS: We identified patients with hypertension aged 40-90 years from a primary care register. Patients with a history of cancer, diabetes mellitus or CVD were excluded. Patients were divided into age groups (40-75 and 76-90), and four groups of SBP 110-129, 130-139 (reference), 140-149 and ≥150 mmHg. We used the Kaplan-Meier estimator to study incidence of AMI, stroke and a composite of the two. Cox proportional-hazards regression was used to estimate hazard ratios for outcomes. RESULTS: We included 31 704 patients: 26 663 were 40-75 years old and 5041 were 76-90 years old. Mean follow-up was 2 years. Although no significant differences in risk of any outcome were found in the younger group, low blood pressure was associated with the lowest risk in the older group. Older patients in the 110-129 mmHg group had a lower incidence of CVD (15.9/1000 vs. 25.3/1000 person-years) than the reference group. After adjustment for covariates, the hazard ratio of CVD in older patients in the 110-129 mmHg group compared with the reference group was 0.60 (95% confidence interval 0.40-0.92). CONCLUSION: Blood pressure levels lower than those currently recommended are not harmful among older patients. The association between lower SBP and lesser risk of CVD may instead suggest a beneficial effect of lower SBP.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Hipertensão/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipertensão/complicações , Incidência , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Modelos de Riscos Proporcionais , Medição de Risco , Acidente Vascular Cerebral/etiologia , Suécia/epidemiologia
11.
Lakartidningen ; 1132016 Sep 23.
Artigo em Sueco | MEDLINE | ID: mdl-27673594
12.
BMJ ; 354: i4070, 2016 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-27492939

RESUMO

OBJECTIVES:  To compare the risk associated with systolic blood pressure that meets current recommendations (that is, below 140 mm Hg) with the risk associated with lower levels in patients who have type 2 diabetes and no previous cardiovascular disease. DESIGN:  Population based cohort study with nationwide clinical registries, 2006-12. The mean follow-up was 5.0 years. SETTING:  861 Swedish primary care units and hospital outpatient clinics. PARTICIPANTS:  187 106 patients registered in the Swedish national diabetes register who had had type 2 diabetes for at least a year, age 75 or younger, and with no previous cardiovascular or other major disease. MAIN OUTCOME MEASURES:  Clinical events were obtained from the hospital discharge and death registers with respect to acute myocardial infarction, stroke, a composite of acute myocardial infarction and stroke (cardiovascular disease), coronary heart disease, heart failure, and total mortality. Hazard ratios were estimated for different levels of baseline systolic blood pressure with clinical characteristics and drug prescription data as covariates. RESULTS:  The group with the lowest systolic blood pressure (110-119 mm Hg) had a significantly lower risk of non-fatal acute myocardial infarction (adjusted hazard ratio 0.76, 95% confidence interval 0.64 to 0.91; P=0.003), total acute myocardial infarction (0.85, 0.72 to 0.99; P=0.04), non-fatal cardiovascular disease (0.82, 0.72 to 0.93; P=0.002), total cardiovascular disease (0.88, 0.79 to 0.99; P=0.04), and non-fatal coronary heart disease (0.88, 0.78 to 0.99; P=0.03) compared with the reference group (130-139 mm Hg). There was no indication of a J shaped relation between systolic blood pressure and the endpoints, with the exception of heart failure and total mortality. CONCLUSIONS:  Lower systolic blood pressure than currently recommended is associated with significantly lower risk of cardiovascular events in patients with type 2 diabetes. The association between low blood pressure and increased mortality could be due to concomitant disease rather than antihypertensive treatment.


Assuntos
Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Mortalidade , Adulto , Idoso , Doença das Coronárias/epidemiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Guias de Prática Clínica como Assunto , Sistema de Registros , Medição de Risco , Acidente Vascular Cerebral/epidemiologia , Suécia/epidemiologia , Sístole
13.
Stroke ; 44(11): 3103-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23982711

RESUMO

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) is a major risk factor for ischemic stroke. This study aims to update the knowledge about AF and associated stroke risk and benefits of anticoagulation. METHODS: We extracted data from the hospital, specialized outpatient, and primary healthcare and drug registries in a Swedish region with 1.56 million residents. We identified all individuals who had received an AF diagnosis during the previous 5 years; all stroke events during 2010; and patients with AF aged ≥50 years who had received warfarin during 2009. RESULTS: AF had been diagnosed in 38 446 subjects who were alive at the beginning of 2010 (prevalence of 3.2% in the adult [≥20 years] population); ≈46% received warfarin therapy. In 2010, there were 4565 ischemic stroke events and 861 intracranial hemorrhages. AF had been diagnosed in 38% of ischemic events (≥50% among those aged ≥80 years) and in 23% of intracranial hemorrhages. An AF diagnosis was often lacking in hospital discharge records after stroke events. Warfarin therapy was associated with an odds ratio of 0.50 (confidence interval, 0.43-0.57) for ischemic stroke and, despite an increased risk of intracranial hemorrhage, an odds ratio of 0.57 (confidence interval, 0.50-0.64) for the overall risk for stroke. CONCLUSIONS: AF is more common than present guidelines suggest. The attributable risk of AF for ischemic stroke increases with age and is close to that of hypertension in individuals aged ≥80 years. Because a majority of patients with AF with increased risk for stroke had not received anticoagulation therapy, there is a large potential for improvement.


Assuntos
Fibrilação Atrial/complicações , Acidente Vascular Cerebral/complicações , Varfarina/efeitos adversos , Varfarina/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/epidemiologia , Estudos de Coortes , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Sistema de Registros , Análise de Regressão , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Suécia/epidemiologia
17.
Curr Med Res Opin ; 22(9): 1813-23, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16968585

RESUMO

OBJECTIVE: NXY-059 is a novel, free-radical trapping, neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischaemic stroke. This study evaluated the safety, tolerability and pharmacokinetics of NXY-059 in the unbound steady-state plasma concentration (Cu(ss)) exposure range of 50-300 micromol/L in healthy young and elderly subjects. RESEARCH DESIGN AND METHODS: The primary objective of this two-centre, randomised, double-blind, placebo-controlled, dose-escalating study was to investigate the safety and tolerability, including renal function parameters and vasoirritative effects, of 8-h and 72-h intravenous infusions of NXY-059 in healthy young (20-45 years) and elderly (55-75 years) male and female subjects. The secondary objective of the study was to evaluate the pharmacokinetics of 8-h and 72-h intravenous infusions of NXY-059 in these subjects, using blood and urine samples taken during and after NXY-059 infusion as well as the doses administered. RESULTS: Of the 104 healthy volunteers who participated in the study, 72 were young and 32 were elderly. The type and incidence of adverse events in NXY-059 and placebo subjects were similar, although headache was more common in the NXY-059 group. Renal function was not altered in either group. Thrombophlebitis was reported in two elderly subjects: one receiving NXY-059 and one receiving placebo. A proportional relationship between AUC and dose for the 8-h and 72-h infusions was observed, and clearance did not change with dose. CONCLUSIONS: NXY-059 was well tolerated at all plasma concentrations tested in both the young and elderly subjects, and no safety concerns were raised. Linear pharmacokinetics were observed following 8-h and 72-h infusions of NXY-059 at doses resulting in an average Cu(ss) in the 52-317 micromol/L range.


Assuntos
Benzenossulfonatos/efeitos adversos , Benzenossulfonatos/farmacocinética , Fármacos Neuroprotetores/efeitos adversos , Fármacos Neuroprotetores/farmacocinética , Adulto , Fatores Etários , Idoso , Benzenossulfonatos/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Scand J Urol Nephrol ; 18(sup79): 53-57, 1984 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27786005

RESUMO

Low basal and stimulated plasma renin activity (PRA) levels have been reported in patients witn diabetic nephropathy (DN). We have measured PRA before and after stimulation with captopril in 28 patients with DN and in 25 control patients. Renal function impairment was similar in both groups. Most patients were treated with furosemide. In 19 patients with DN the PRA-response to dihydralazine was also studied. PRA before and after captopril were higher in the DN than in the control group (P < 0.001). PRA increased from 4.6 ± 3.6 to 6.3 ± 5.3 in the DN, and from 1.8 ± 2.7 to 2.7 ± 3.4 in the control patients. The increases in PRA, caused by decreased angiotensin II feed-back inhibition, were comparable. PRA did not increase after dihydralazine despite a pronounced blood-pressure reduction. The difference in response to these stimuli indicate selective lesions involving both the sympathetic innervation and the renal baroreceptor function in DN. Overhydration is a plausible explanation to the low PRA earlier reported in DN. The results thus indicate that a preserved renin secretion capacity is present in DN. Differences in PRA between the both groups can only partly be explained by other factors than DN. Our findings indicate a role for the reninangiotensin-system in hypertension in DN.

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