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3.
Angiology ; 71(2): 139-149, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31694385

RESUMO

The relative superiority of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on long-term clinical outcomes in patients with non-ST-segment elevation myocardial infarction (NSTEMI) with preserved left ventricular systolic function in the era of new generation drug-eluting stents is not well established. A total of 6436 patients with NSTEMI (ACEIs group: n = 3965 vs ARBs group: n = 2471) were enrolled. The major clinical end point was the occurrences of major adverse cardiac events (MACEs), defined as all-cause death, recurrent myocardial infarction (re-MI), and any repeat revascularization. After propensity score matching analysis, the cumulative incidences of MACEs (hazard ratio, 1.334; 95% confidence interval, 1.045-1.703; P = .021), any repeat revascularization, and target vessel revascularization (TVR) in the ARB group were significantly higher than that in the ACEI group. However, the cumulative incidences of all-cause death, cardiac death, re-MI, target lesion revascularization, and non-TVR were similar between the 2 groups. Hence, although the mortality and re-MI reduction benefits were similar between the 2 groups, the ACEIs group showed more prominent ability to decrease the occurrences of MACEs, any repeat revascularization, and TVR compared to the ARBs group in these patients during a 2-year follow-up period.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Stents Farmacológicos , Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sístole/fisiologia , Função Ventricular Esquerda/fisiologia
4.
Life Sci ; 242: 117181, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31863771

RESUMO

AIMS: Angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) which have been used in the treatment of cardiovascular diseases, have also been shown to have anti-tumor effects against various cancers that include renal cancer. The aim of current paper was to explore the potential clinical impact of ACEI/ARB inhibitors in renal cancer. MAIN METHODS: We used several databases: EMBASE, PubMed and the Cochrane library, to identify clinical studies that assessed the relationship between ACEIs/ARBs treatment and risk of renal cancer incidence or survival of renal cancer patients. The hazard ratio (HR) with 95% confidence intervals were obtained for assessing the relationship between ACEIs/ARBs and renal cancer mortality. KEY FINDING: The HR for the relationship between ASIs use and survival of renal cancer indicated that patients with renal cancer being treated with ACEIs/ARBs had a significantly lower mortality than non-user (HR 0.723, 95% CI 0.568-0.921, p = 0.009). The HR for the relationship between ACEIs use and survival of renal cancer indicated that patients with renal cancer that used ACEIs had a higher mortality than non-users (HR 1.352, 95% CI 0.917-1.991, p = 0.128). The HR for the relationship between ARBs use and survival of renal cancer indicated that patients with renal cancer that used ARBs had a decreased of mortality than non-users (HR 0.818, 95% CI 0.691-0.969, p = 0.02). SIGNIFICANCE: This meta-analysis demonstrated that treatment with ACEIs/ARBs may improve renal cancer survival and reduce the mortality of patients with renal cancer.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Humanos , Neoplasias Renais/mortalidade , Análise de Sobrevida
5.
Medicine (Baltimore) ; 98(49): e17963, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804307

RESUMO

Renin angiotensin aldosterone system inhibitors (RAASi) and diuretics are among the most frequently prescribed anti-hypertensives. Individuals with chronic kidney disease (CKD) are particularly at risk for electrolyte disturbances and kidney injury but the appropriate use of lab monitoring following RAASi or diuretic initiation is uncertain in CKD.We describe the frequency and time interval of lab monitoring during initiation of RAASi and diuretics in CKD and assess whether close lab monitoring associates with one-year risk of emergency department (ED) visit or hospitalization.We evaluated an observational cohort of 8,217 individuals with stage 3-5 non-dialysis CKD newly prescribed a RAASi (52.3%) or diuretic (47.7%) from thirty-six primary care offices affiliated with Brigham and Women's Hospital and Massachusetts General Hospital between 2009 and 2011.Overall, 3306 (40.2%) individuals did not have pre-prescription labs done within 2 weeks, and 5957 (72.5%) did not have post-prescription labs done within 2 weeks which includes 524 (6.4%) individuals without post-prescription within 1 year. Close monitoring occurred in only 1547 (20.1%) and was more likely in individuals prescribed diuretics compared to RAASi (adjusted OR 1.39; 95%CI 1.20-1.62), with CKD stage 4,5 compared with stage 3 (adjusted OR 1.47; 95%CI 1.16-1.86) and with cardiovascular disease (adjusted OR 1.42; 95%CI 1.21-1.66). Close monitoring was not associated with decreased risk of ED visit or hospitalization.Close lab monitoring during initiation of RAASi or diuretics was more common in participants with cardiovascular disease and advanced CKD suggesting physicians selected high-risk individuals for close monitoring. As nearly 80% of individuals did not receive close lab monitoring there may be value in future research on electronic physician decision tools targeted at lab monitoring.


Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Testes de Função Renal/estatística & dados numéricos , Insuficiência Renal Crônica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Boston , Comorbidade , Diuréticos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Potássio/sangue , Sistema Renina-Angiotensina/efeitos dos fármacos , Índice de Gravidade de Doença , Fatores Socioeconômicos
6.
Medicine (Baltimore) ; 98(47): e17978, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764806

RESUMO

RATIONALE: Marfan syndrome is a rare cause of heart failure due to primary or secondary cardiomyopathy. Recently, sacubitril/valsartan-an angiotensin receptor blocker-neprilysin inhibitor-has been added in clinical practice as a standard therapy for heart failure. To our knowledge, there are no data on sacubitril/valsartan's effects on cardiovascular outcomes in patients with Marfan syndrome. PATIENT CONCERNS: A 24-year-old man was admitted to our Internal Medicine Department due to dyspnea, ascites, and leg swelling. Arterial blood gas analysis revealed severe hypoxemia with respiratory and metabolic alkalosis. Hilar congestion was highlighted on chest x-ray. DIAGNOSES: Recurrent acute decompensated heart failure with reduced ejection fraction despite optimal medical therapy in Marfan-related cardiomyopathy. INTERVENTIONS AND OUTCOMES: Sacubitril/valsartan was added to optimal medical therapy after hemodynamic stabilization allowing progressive clinical, laboratoristic, and echocardiographic improvement. Patient maintained a free survival from heart failure and a good quality of life until 9-month follow-up. LESSONS: Sacubitril/valsartan should be effective on pathophysiologic mechanisms and cardiovascular outcomes of Marfan syndrome-related cardiovascular complications.


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Síndrome de Marfan/complicações , Tetrazóis/uso terapêutico , Humanos , Masculino , Resultado do Tratamento , Adulto Jovem
7.
Medicine (Baltimore) ; 98(47): e18050, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764831

RESUMO

BACKGROUND: This study aims to systematically explore the efficacy of sacubitril valsartan sodium tablet (SVST) for the treatment of chronic heart failure (CHF). METHODS: Nine electronic databases, including PUBMED, Cochrane Library, EMBASE, PsycINFO, Web of Science, Allied and Complementary Medicine Database, WANGFANG, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched. Randomized controlled trials on SVST in the treatment of CHF will be collected. The search time limit will be from the establishment of each electronic database until June 1, 2019. Two authors will independently select the literature, carry out the data, and assess the methodological quality. RESULTS: This study will systematically investigate the efficacy and safety of SVST for CHF. The outcomes consist of all-cause mortality, change in body weight, urine output, change in serum sodium; and incidence of any expected and unexpected adverse events. CONCLUSION: The findings of this study will summarize from evidence-based medicine and a scientific basis for the efficacy and safety of SVST in the clinical treatment of CHF. PROSPERO REGISTRATION NUMBER: PROSPERO CRD42019138882.


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisão Sistemática como Assunto , Tetrazóis/uso terapêutico , Doença Crônica , Humanos , Projetos de Pesquisa , Comprimidos , Resultado do Tratamento
8.
Lancet ; 394(10211): 1816-1826, 2019 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-31668726

RESUMO

BACKGROUND: Uncertainty remains about the optimal monotherapy for hypertension, with current guidelines recommending any primary agent among the first-line drug classes thiazide or thiazide-like diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, dihydropyridine calcium channel blockers, and non-dihydropyridine calcium channel blockers, in the absence of comorbid indications. Randomised trials have not further refined this choice. METHODS: We developed a comprehensive framework for real-world evidence that enables comparative effectiveness and safety evaluation across many drugs and outcomes from observational data encompassing millions of patients, while minimising inherent bias. Using this framework, we did a systematic, large-scale study under a new-user cohort design to estimate the relative risks of three primary (acute myocardial infarction, hospitalisation for heart failure, and stroke) and six secondary effectiveness and 46 safety outcomes comparing all first-line classes across a global network of six administrative claims and three electronic health record databases. The framework addressed residual confounding, publication bias, and p-hacking using large-scale propensity adjustment, a large set of control outcomes, and full disclosure of hypotheses tested. FINDINGS: Using 4·9 million patients, we generated 22 000 calibrated, propensity-score-adjusted hazard ratios (HRs) comparing all classes and outcomes across databases. Most estimates revealed no effectiveness differences between classes; however, thiazide or thiazide-like diuretics showed better primary effectiveness than angiotensin-converting enzyme inhibitors: acute myocardial infarction (HR 0·84, 95% CI 0·75-0·95), hospitalisation for heart failure (0·83, 0·74-0·95), and stroke (0·83, 0·74-0·95) risk while on initial treatment. Safety profiles also favoured thiazide or thiazide-like diuretics over angiotensin-converting enzyme inhibitors. The non-dihydropyridine calcium channel blockers were significantly inferior to the other four classes. INTERPRETATION: This comprehensive framework introduces a new way of doing observational health-care science at scale. The approach supports equivalence between drug classes for initiating monotherapy for hypertension-in keeping with current guidelines, with the exception of thiazide or thiazide-like diuretics superiority to angiotensin-converting enzyme inhibitors and the inferiority of non-dihydropyridine calcium channel blockers. FUNDING: US National Science Foundation, US National Institutes of Health, Janssen Research & Development, IQVIA, South Korean Ministry of Health & Welfare, Australian National Health and Medical Research Council.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Adulto , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Criança , Estudos de Coortes , Pesquisa Comparativa da Efetividade/métodos , Bases de Dados Factuais , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Medicina Baseada em Evidências/métodos , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/prevenção & controle , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Adulto Jovem
9.
Rev Med Suisse ; 15(667): 1882-1886, 2019 Oct 16.
Artigo em Francês | MEDLINE | ID: mdl-31617977

RESUMO

The association of an angiotensin II receptor antagonist and a neprilysin inhibitor (ARNI or Angiotensin Receptor-Neprilysin Inhibitor) is a new actor in the management of heart failure with reduced left ventricular ejection fraction (LVEF). The PARADIGM-HF trial performed in outpatients with a LVEF ≤ 35-40 % demonstrated that sacubitril-valsartan was superior to enalapril in reducing cardiovascular mortality and heart failure hospitalizations. Precautions in the initiation of sacubitril-valsartan, its use as well as its place in the drug management strategy for chronic heart failure are described in the present review. Additional data in patients hospitalized with reduced LVEF, in patients with LVEF > 45 % as well as the effects on blood pressure, renal or cognitive functions are presented.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Neprilisina/antagonistas & inibidores , Aminobutiratos/farmacologia , Aminobutiratos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Cognição/efeitos dos fármacos , Enalapril/farmacologia , Enalapril/uso terapêutico , Insuficiência Cardíaca/metabolismo , Humanos , Rim/efeitos dos fármacos , Neprilisina/metabolismo , Tetrazóis/farmacologia , Tetrazóis/uso terapêutico , Resultado do Tratamento
10.
Cardiovasc Hematol Agents Med Chem ; 17(2): 144-151, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31629400

RESUMO

INTRODUCTION: Recent findings have shown that in Acute Ischemic Stroke (AIS) patients, elevated troponin is associated with increased mortality. However, due to concerns of cerebral hypoperfusion and hemorrhagic transformation, current practice has been slow to apply proven cardiac therapies to these patients. This study aims to determine this rate of utilization. MATERIALS AND METHODS: A single-center review of 83 patients with AIS and measured troponin was conducted. Patients were stratified based on elevated and non-elevated troponin. Between groups, we measured the utilization of evidence-based cardiac therapies and used a univariate logistic regression to compare outcomes of mortality, re-hospitalization, recurrent acute ischemic stroke, recurrent acute myocardial infarction, and a composite of these outcomes. RESULTS: Of 83 patients, 25 had elevated troponin and 58 had non-elevated troponin. There was no statistical difference in the use of cardiac therapies between the two groups. Adenosine diphosphate P2Y12 antagonists were infrequently used in both elevated and non-elevated troponin groups at 32% vs. 24% (p = 0.64), as were Angiotensin-Converting Enzyme Inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) at 56% vs. 69% (p = 0.38). Those in the elevated troponin group encountered a statistically significant increase in composite endpoint 64% vs. 33% (Odds Ratio [OR] 7.28, 95% Confidence interval [CI] 2.19-28.88, p<0.01). CONCLUSION: Cardiac therapies are underutilized in patients with acute ischemic stroke and elevated troponin levels. In turn, this low usage may explain the increase in morbidity and mortality seen in these patients and the use of such therapies should be considered when treating this subset of patients as the cardio protective nature of these therapies may outweigh the risks associated with them in AIS patients.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infarto do Miocárdio/prevenção & controle , Antagonistas do Receptor Purinérgico P2Y/uso terapêutico , Acidente Vascular Cerebral/sangue , Troponina/sangue , Idoso , Isquemia Encefálica/sangue , Isquemia Encefálica/complicações , Feminino , Humanos , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/complicações
11.
Mayo Clin Proc ; 94(11): 2220-2229, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31619367

RESUMO

OBJECTIVE: To assess the patterns of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACE-I/ARB) discontinuation in the setting of chronic kidney disease (CKD) progression in real-world clinical practice. PATIENTS AND METHODS: We identified incident ACE-I/ARB users with a baseline estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 and without end-stage renal disease in the Geisinger Health System between January 1, 2004, and December 31, 2015. We investigated the associations of CKD stage, hospitalizations with and without acute kidney injury (AKI), serum potassium, bicarbonate level, thiazide, and loop diuretic use with ACE-I/ARB discontinuation. RESULTS: Among the 53,912 ACE-I/ARB users, the mean age was 59.9 years, and 50.6% were female. More than half of users discontinued ACE-I/ARB within 5 years of therapy initiation. The risk of ACE-I/ARB discontinuation increased with more advanced CKD stage. For example, patients who initiated ACE-I/ARB with CKD stage G4 (eGFR: 15-29 mL/min/1.73 m2) were 2.09-fold (95% CI, 1.87-2.34) more likely to discontinue therapy than those with eGFR ≥ 90 mL/min/1.73 m2. Potassium level greater than 5.3 mEq/L, systolic blood pressure ≤ 90 mm Hg, bicarbonate level < 22 mmol/L, and intervening hospitalization-particularly AKI-related-were also strong risk factors for ACE-I/ARB discontinuation. Thiazide diuretic use was associated with lower risk, whereas loop diuretic use was associated with higher risk of discontinuation. CONCLUSION: In a real-world cohort, discontinuation of ACE-I/ARB was common, particularly in patients with lower eGFR. Hyperkalemia, hypotension, low bicarbonate level, and hospitalization (AKI-related, in particular) were associated with a higher risk of ACE-I/ARB discontinuation. Additional studies are needed to evaluate the risk-benefit balance of discontinuing ACE-I/ARB in the setting of CKD progression.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Adesão à Medicação , Insuficiência Renal Crônica/tratamento farmacológico , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
12.
F1000Res ; 82019.
Artigo em Inglês | MEDLINE | ID: mdl-31583081

RESUMO

Since the association of microalbuminuria (MAU) with cardiovascular (CV) risk was described, a huge number of reports have emerged. MAU is a specific integrated marker of CV risk and targets organ damage in patients with hypertension, chronic kidney disease (CKD), and diabetes and its recognition is important for identifying patients at a high or very high global CV risk. The gold standard for diagnosis is albumin measured in 24-hour urine collection (normal values of less than 30 mg/day, MAU of 30 to 300 mg/day, macroalbuminuria of more than 300 mg/day) or, more practically, the determination of urinary albumin-to-creatinine ratio in a urine morning sample (30 to 300 mg/g). MAU screening is mandatory in individuals at risk of developing or presenting elevated global CV risk. Evidence has shown that intensive treatment could turn MAU into normoalbuminuria. Intensive treatment with the administration of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, in combination with other anti-hypertensive drugs and drugs covering other aspects of CV risk, such as mineralocorticoid receptor antagonists, new anti-diabetic drugs, and statins, can diminish the risk accompanying albuminuria in hypertensive patients with or without CKD and diabetes.


Assuntos
Albuminúria/diagnóstico , Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Hipertensão/tratamento farmacológico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Diabetes Mellitus , Humanos , Hipertensão/complicações , Insuficiência Renal Crônica/complicações , Fatores de Risco
13.
Nat Commun ; 10(1): 4202, 2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519895

RESUMO

It remains disputable about perioperative use of renin-angiotensin system inhibitors (RASi) and their outcome effects. This multicenter retrospective cohort study examines association between use of perioperative RASi and outcomes in patients undergoing coronary artery bypass graft and/or valve surgery. After the exclusion, the patients are divided into 2 groups with or without preoperative RASi (PreRASi, n = 8581), or 2 groups with or without postoperative RASi (PostRASi, n = 8130). With using of propensity scores matching to reduce treatment selection bias, the study shows that PreRASi is associated with a significant reduction in postoperative 30-day mortality compared with without one (3.41% vs. 5.02%); PostRASi is associated with reduced long-term mortality rate compared with without one (6.62% vs. 7.70% at 2-year; 17.09% vs. 19.95% at 6-year). The results suggest that perioperative use of RASi has a significant benefit for the postoperative and long-term survival among patients undergoing cardiac surgery.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Assistência Perioperatória , Sistema Renina-Angiotensina/efeitos dos fármacos , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Ponte de Artéria Coronária , Feminino , Valvas Cardíacas/cirurgia , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
14.
Lancet ; 394(10205): 1254-1263, 2019 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-31447116

RESUMO

BACKGROUND: Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and ß blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and ß blockers in patients with HFrEF. METHODS: We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and ß blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF. FINDINGS: Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p<0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p<0·0001) and heights (162 [7] cm vs 174 [8] cm, p<0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and ß blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and ß blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and ß blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels. INTERPRETATION: This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and ß blockers than men, and brings into question what the true optimal medical therapy is for women versus men. FUNDING: European Commission.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Estudos Prospectivos , Fatores Sexuais , Volume Sistólico/efeitos dos fármacos
15.
Int J Clin Pharmacol Ther ; 57(10): 483-488, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31426904

RESUMO

AIM: The aim of this study was to investigate the potential association between antihypertensive therapy and the incidence of Parkinson's disease (PD) in patients followed in general practices in Germany. MATERIALS AND METHODS: This study included patients aged ≥ 40 who had received initial diagnoses of PD in 1,203 general practices in Germany between January 2013 and December 2017 (index date). After applying similar inclusion criteria, PD cases were matched to non-PD controls using propensity scores based on age, sex, and treating physician. The primary outcome of the study was the incidence of PD as a function of the use of antihypertensive drugs (diuretics, ß-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers). Logistic regression models were conducted to study the association between the use of antihypertensive drugs and the incidence of PD after adjusting for codiagnoses and antihypertensive cotherapy. RESULTS: The present study included 9,127 patients with PD and 9,127 patients without PD (mean age: 75.8 years; 48.4% women). The at-least-once use of diuretics (44.8% versus 38.4%; odds ratio (OR) = 1.23 (1.15-1.32)) was associated with an increased incidence of PD. However, this effect was not maintained for a therapy duration of at least 3 years, and no association was observed between the diuretic therapy duration and PD incidence. For all other antihypertensive drug classes, we found no significant associations with PD incidence. CONCLUSION: No association was found between antihypertensive therapy duration and PD incidence. Further epidemiological studies are needed to compare the effects of subclasses of antihypertensives on PD.


Assuntos
Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Doença de Parkinson/complicações , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/efeitos adversos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/efeitos adversos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Diuréticos/efeitos adversos , Diuréticos/uso terapêutico , Feminino , Medicina Geral , Alemanha , Humanos , Hipertensão/complicações , Incidência , Masculino
16.
J Physiol Pharmacol ; 70(2)2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31443094

RESUMO

Urocortin 2 (Ucn2) - corticotropin-releasing hormone receptor 2 signalling has favourable effects in the cardiovascular system, including vasodilation, lowering of blood pressure and systemic peripheral resistance, increase in cardiac output and cardiac contractility, as well as cardioprotection against ischemia-reperfusion injury. Vasodilation and lowering of blood pressure seem to be very interesting and important effects, but their mechanism and interaction with the antihypertensive drugs have not been evaluated. The aim of the present study was to assess the relationship between Ucn2 concentration and antihypertensive therapy in patients with primary hypertension. We examined a group of 65 patients with primary hypertension receiving at least 3 antihypertensive drugs. In all of them plasma level of Ucn2, anthropometric measurements, biochemical tests, ambulatory blood pressure monitoring (ABPM), and echocardiography were performed. There were no differences in Ucn2 level related to beta-blockers, calcium channel blockers or diuretics, but we observed that in patients treated with angiotensin converting enzyme inhibitors (ACEI) (n = 52) serum Ucn2 levels were significantly higher than in patients treated with angiotensin-receptor blockers (ARBs) (n = 13) (10.93 versus 5.56 ng/mL; P < 0.05). Moreover, we did not observe any differences in terms of blood pressure on ABPM, biochemical measurements, left ventricular mass index, or presence of diabetes. In addition, in a small subgroup receiving alpha-blockers we also found a lower level of Ucn2, with coexisting higher systolic blood pressure at night, higher left ventricle mass index (LVMI) and more frequent occurrences of diabetes compared to non-alpha-blockers. Our findings suggest that the hypotensive action of renin-angiotensin-aldosterone system blockade may be related to the urocortin system. Ucn2 may be an important element in the mosaic of blood pressure-lowering factors in patients treated for essential hypertension.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Hormônio Liberador da Corticotropina/metabolismo , Hipertensão/tratamento farmacológico , Urocortinas/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Monitorização Ambulatorial da Pressão Arterial/métodos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Feminino , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Humanos , Hipertensão/metabolismo , Masculino , Pessoa de Meia-Idade , Sistema Renina-Angiotensina/efeitos dos fármacos , Resistência Vascular/efeitos dos fármacos
17.
BMC Pharmacol Toxicol ; 20(1): 44, 2019 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-31349878

RESUMO

BACKGROUND: This analysis was designed to investigate the relationship between drug application and mortality rate in Chinese older coronary artery disease (CAD)/chronic heart failure (CHF) patients with and without low glomerular filtration rate (GFR). METHODS: All 1050 Chinese hospitalized patients with diagnosed CAD were included in this analysis, and Cox Regression was used to analyze the relationship between drug application and mortality rate after multivariate adjustment. Low GFR was defined as GFR < 60 ml/min/1.73m2. RESULTS: There were 372 patients (35.4%) with low GFR in patients with CAD (1050 patients), and 168 patients (51.4%) in patients with CHF (327 patients). In CAD patients without low GFR, clopidogrel [P = 0.028, odds ratio (OR): 0.620, 95% confidence interval (CI): 0.404-0.951] rather than aspirin (P = 0.173) was significantly associated with lower mortality rate. Statins (P < 0.001, OR: 0.287, 95% CI: 0.180-0.456) were significantly associated with lower mortality rate. In CAD patients with low GFR, aspirin, clopidogrel and statins had no significant relationship with mortality rate (P > 0.05 for all). In CHF patients without low GFR, statins were significantly associated with lower mortality rate (P < 0.001, OR: 0.220, 95% CI: 0.098-0.490). In CHF patients with low GFR, statins had no significant relationship with mortality rate (P > 0.05 for all). CONCLUSION: Clopidogrel but not aspirin was beneficial in Chinese older CAD patients without low GFR rather than those with low GFR, and statins benefited for Chinese older CAD/CHF patients without low GFR rather than those with low GFR. These discoveries might offer some help for the therapy of Chinese older patients with cardiovascular/renal diseases.


Assuntos
Doença da Artéria Coronariana , Taxa de Filtração Glomerular , Insuficiência Cardíaca , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Aspirina/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Digoxina/uso terapêutico , Uso de Medicamentos , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Hospitalização , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nitratos/uso terapêutico
18.
Int J Mol Sci ; 20(14)2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31336656

RESUMO

Brain natriuretic peptide (BNP) is an important biomarker for patients with heart failure, hypertension and cardiac hypertrophy. Although it is known that BNP levels are relatively higher in patients with chronic kidney disease and no heart disease, the mechanism remains unknown. Here, we review the functions and the roles of BNP in the heart-kidney interaction. In addition, we discuss the relevant molecular mechanisms that suggest BNP is protective against chronic kidney diseases and heart failure, especially in terms of the counterparts of the renin-angiotensin-aldosterone system (RAAS). The renal medulla has been reported to express depressor substances. The extract of the papillary tips from kidneys may induce the expression and secretion of BNP from cardiomyocytes. A better understanding of these processes will help accelerate pharmacological treatments for heart-kidney disease.


Assuntos
Coração/fisiologia , Rim/fisiologia , Peptídeo Natriurético Encefálico/metabolismo , Transdução de Sinais , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Animais , Suscetibilidade a Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Peptídeo Natriurético Encefálico/genética , Neprilisina/antagonistas & inibidores , Sistema Renina-Angiotensina/efeitos dos fármacos , Vasoconstritores/farmacologia , Vasoconstritores/uso terapêutico
19.
World J Gastroenterol ; 25(20): 2524-2538, 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31171895

RESUMO

BACKGROUND: Neoangiogenesis is one of the key pathogenetic mechanisms in hepatocellular carcinoma (HCC). Modulation of the renin-angiotensin system (RAS) by angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) seems to be a possible adjuvant therapy for HCC, due to the anti-angiogenic and anti-fibrogenic activity of these drugs. AIM: To elucidate the role of ARBs and ACE-Is in HCC. METHODS: We performed an electronic search of the literature using the most accessed online databases (PubMed, Cochrane library, Scopus and Web of Science), entering the query terms "angiotensin-converting enzyme inhibitors" OR "ACE inhibitors" OR "ACE-I" AND "hepatocarcinoma*" OR "hepatocellular carcinoma; moreover "angiotensin II type 1 receptor blockers" OR "ARBs" AND "hepatocarcinoma*" OR "hepatocellular carcinoma". Eligibility criteria were: (1) prospective or retrospective clinical studies; (2) epidemiological studies; and (3) experimental studies conducted in vivo or in vitro. Abstracts, conference papers, and reviews were excluded a priori. We limited our literature search to articles published in English, in peer-reviewed journals. RESULTS: Thirty-one studies were selected. Three interventional studies showed that ACE-Is had a significant protective effect on HCC recurrence only when used in combination with vitamin K or branched chain aminoacids, without a significant increase in overall survival. Of six retrospective observational studies, mainly focused on overall survival, only one demonstrated a prolonged survival in the ACE-Is group, whereas the two that also evaluated tumor recurrence showed conflicting results. All experimental studies displayed beneficial effects of RAS inhibitors on hepatocarcinogenesis. Numerous experimental studies, conducted either on animals and cell cultures, demonstrated the anti-angiogenetic and antifibrotic effect of ACE-Is and ARBs, thanks to the suppression of some cytokines such as vascular endothelial growth factor, hypoxia-inducible factor-1a, transforming growth factor-beta and tumor necrosis factor alpha. All or parts of these mechanisms were demonstrated in rodents developing fewer HCC and preneoplastic lesions after receiving such drugs. CONCLUSION: In humans, RAS inhibitors - alone or in combination - significantly suppressed the cumulative HCC recurrence, without prolonging patient survival, but some limitations intrinsic to these studies prompt further investigations.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia/prevenção & controle , Neovascularização Patológica/prevenção & controle , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/mortalidade , Quimioterapia Adjuvante/métodos , Modelos Animais de Doenças , Quimioterapia Combinada/métodos , Hepatectomia , Humanos , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/cirurgia , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/mortalidade , Recidiva Local de Neoplasia/epidemiologia , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Sistema Renina-Angiotensina/efeitos dos fármacos , Resultado do Tratamento
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