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1.
BMC Med Genet ; 20(1): 183, 2019 11 14.
Artículo en Inglés | MEDLINE | ID: mdl-31727004

RESUMEN

BACKGROUND: It is well established that long-term use of aspirin can cause gastric mucosal injury. ACEIs and ARBs are inversely related to gastric ulcer development. This study aimed to evaluate the relationship between SLCO1B1 polymorphisms, which can affect ACEI and ARB transport, and gastric mucosal erosion in elderly male Chinese patients with cardiovascular disease who use aspirin. METHODS: Patients taking aspirin and an ACEI or ARB concomitantly who had undergone endoscopic screening for gastric erosion were analyzed for SLCO1B1 polymorphisms by a TaqMan assay. RESULTS: The frequency of the SLCO1B1*1b/*1b diplotype (42% vs. 24%; p = 0.002) was significantly higher in the gastric mucosal erosion group than in the control group. After adjustment for significant factors, SLCO1B1*1b/*1b (OR, 2.64; 95% CI, 1.59-4.17; p < 0.05) was found to be associated with gastric mucosal erosion in aspirin users. CONCLUSIONS: The presence of the SLCO1B1*1b/*1b diplotype may be a risk factor for aspirin-induced gastric mucosal erosion in elderly Chinese men taking aspirin and an ACEI or ARB concomitantly.


Asunto(s)
Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Aspirina/efectos adversos , Mucosa Gástrica/patología , Predisposición Genética a la Enfermedad , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/genética , Anciano , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Aspirina/administración & dosificación , Estudios de Casos y Controles , China , Quimioterapia Combinada , Frecuencia de los Genes , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple
2.
Yakugaku Zasshi ; 139(11): 1457-1462, 2019.
Artículo en Japonés | MEDLINE | ID: mdl-31685742

RESUMEN

Recently, there have been reports that the combination of renin angiotensin inhibitors, diuretics, and non-steroidal anti-inflammatory drugs increases the risk of acute kidney injury (AKI). This combination has been dubbed the "Triple Whammy". However, there have been no reports about its chronic effects on the kidney. In this study, we investigated the chronic effects of the "Triple Whammy" on kidney function. There were 203 outpatients who were prescribed this combination in our hospital for 5 years. We excluded patients who could also confirm the combination in the previous year and patients for whom laboratory data were unavailable, thus, leaving a target patient group of 95 patients. The average estimated glomerular filtration rate (eGFR) decreased significantly from 62.6 to 58.9 mL/min/1.73 m2 immediately after administering the combination (p<0.01). Although no patients were diagnosed with AKI within 90 days after being administered the combination, 7.4% of patients exhibited a ≥25% reduction in eGFR compared with that before commencing the combination. Correlation analysis of gender, age, past renal function, and renal function change demonstrated that eGFR before administration of the combination negatively correlated with changes in eGFR (p<0.01). Considering the effects of individual differences, eGFR changes before and after administering the combination were compared using a case-crossover design and eGFR after administering the combination was found to be significantly reduced (p<0.01). Therefore, it appears that the "Triple Whammy" may cause not only AKI but also chronic renal degeneration.


Asunto(s)
Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Diuréticos/efectos adversos , Tasa de Filtración Glomerular/efectos de los fármacos , Insuficiencia Renal Crónica/inducido químicamente , Lesión Renal Aguda/inducido químicamente , Anciano , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antiinflamatorios no Esteroideos/administración & dosificación , Estudios Cruzados , Diuréticos/administración & dosificación , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/fisiopatología
3.
Rev Cardiovasc Med ; 20(3): 111-120, 2019 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-31601085

RESUMEN

Randomized controlled trials have demonstrated the benefits of guideline-directed medical therapy in the outpatient setting for treatment of chronic heart failure. However, the benefits of continuation (or discontinuation) of major chronic heart failure therapies when treating acute heart failure during hospitalization are less clear. Real and anticipated worsening renal function, hyperkalemia and hypotension are the three major reasons for discontinuation of renin-angiotensin-aldosterone system inhibitors during hospitalization, and a failure to resume renin-angiotensin-aldosterone system inhibitors before discharge could worsen cardiovascular outcomes. Available data, mostly observational, shows that continuation or initiation of renin-angiotensin-aldosterone system inhibitors appears efficacious, safe, and well tolerated in majority of acute heart failure patients during hospitalization. Worsening renal function portends poor prognosis only if associated with congestion in acute heart failure, and clinicians should not de-escalate diuretic therapy routinely for worsening renal function.


Asunto(s)
Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Síndrome Cardiorrenal/tratamiento farmacológico , Diuréticos/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Admisión del Paciente , Sistema Renina-Angiotensina/efectos de los fármacos , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Síndrome Cardiorrenal/diagnóstico , Síndrome Cardiorrenal/mortalidad , Síndrome Cardiorrenal/fisiopatología , Toma de Decisiones Clínicas , Diuréticos/efectos adversos , Esquema de Medicación , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Factores de Riesgo , Resultado del Tratamiento
4.
Medicine (Baltimore) ; 98(39): e17296, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31574852

RESUMEN

The angiotensin-receptor-neprilysin inhibitor (ARNI) reduced cardiovascular deaths and heart failure hospitalization in patients with heart failure of reduced ejection fraction (HFrEF). Its role in non-HFrEF patients was not clear. This study aims to answer this question.In this retrospective study, we enrolled 928 patients diagnosed with non-HFrEF, 492 of them received angiotensin converting enzyme inhibitor (ACEI) and the rest 436 received angiotensin-receptor-neprilysin inhibitor. Outcomes were compared by Kaplan-Meier survival analysis and various clinical parameters were investigated using Cox multivariable analysis, followed by interaction analysis. Minnesota living with heart failure Questionnaire (MLHFQ) was employed as one of the criteria to assess heart failure outcome.The cardiovascular (CV) death or HF hospitalization at 24 months occurred in 49 patients in ACEI group compared with 31 in ARNI group (Hazard Ratio (HR): 1.231, 95% confidence Interval (CI): 1.080-2.460, P = .031). And ARNI showed better prognosis of HF hospitalization (HR: 1.283, 95%CI: 1.065-1.360, P = .038). Cumulative Kaplan-Meier estimates of endpoints, ARNI could reduce the incidence of CV death or HF hospitalization (P = .042) and HF hospitalization (P = .035). The stratified analysis revealed that participants with age less than 70 years old had a lower incidence of CV death or HF hospitalization (HR: 1.194, 95%CI: 1.011-1992, P = .031) after treated with ARNI. Patients received diuretics could benefit from ARNI (HR: 1.383, 95%CI: 1.082-1.471, P = .019). Similar results were also observed in patients with heart rate lower than 90 bpm (HR: 1.556, 95%CI: 1.045-2.386, P = .003) and patients with atrial fibrillation history (HR: 1.873, 95%CI: 1.420-2.809, P = .011). ARNI could improve the quality of life both from the total, emotional and physical aspects.ARNI is an efficacy treatment strategy to improve the outcome and quality of life in patients with non-HFrEF.


Asunto(s)
Antagonistas de Receptores de Angiotensina , Insuficiencia Cardíaca , Hospitalización/estadística & datos numéricos , Neprilisina/antagonistas & inhibidores , Calidad de Vida , Volumen Sistólico , Anciano , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/efectos adversos , China/epidemiología , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/psicología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento , Función Ventricular Izquierda
5.
N Engl J Med ; 381(17): 1609-1620, 2019 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-31475794

RESUMEN

BACKGROUND: The angiotensin receptor-neprilysin inhibitor sacubitril-valsartan led to a reduced risk of hospitalization for heart failure or death from cardiovascular causes among patients with heart failure and reduced ejection fraction. The effect of angiotensin receptor-neprilysin inhibition in patients with heart failure with preserved ejection fraction is unclear. METHODS: We randomly assigned 4822 patients with New York Heart Association (NYHA) class II to IV heart failure, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril-valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The primary outcome was a composite of total hospitalizations for heart failure and death from cardiovascular causes. Primary outcome components, secondary outcomes (including NYHA class change, worsening renal function, and change in Kansas City Cardiomyopathy Questionnaire [KCCQ] clinical summary score [scale, 0 to 100, with higher scores indicating fewer symptoms and physical limitations]), and safety were also assessed. RESULTS: There were 894 primary events in 526 patients in the sacubitril-valsartan group and 1009 primary events in 557 patients in the valsartan group (rate ratio, 0.87; 95% confidence interval [CI], 0.75 to 1.01; P = 0.06). The incidence of death from cardiovascular causes was 8.5% in the sacubitril-valsartan group and 8.9% in the valsartan group (hazard ratio, 0.95; 95% CI, 0.79 to 1.16); there were 690 and 797 total hospitalizations for heart failure, respectively (rate ratio, 0.85; 95% CI, 0.72 to 1.00). NYHA class improved in 15.0% of the patients in the sacubitril-valsartan group and in 12.6% of those in the valsartan group (odds ratio, 1.45; 95% CI, 1.13 to 1.86); renal function worsened in 1.4% and 2.7%, respectively (hazard ratio, 0.50; 95% CI, 0.33 to 0.77). The mean change in the KCCQ clinical summary score at 8 months was 1.0 point (95% CI, 0.0 to 2.1) higher in the sacubitril-valsartan group. Patients in the sacubitril-valsartan group had a higher incidence of hypotension and angioedema and a lower incidence of hyperkalemia. Among 12 prespecified subgroups, there was suggestion of heterogeneity with possible benefit with sacubitril-valsartan in patients with lower ejection fraction and in women. CONCLUSIONS: Sacubitril-valsartan did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among patients with heart failure and an ejection fraction of 45% or higher. (Funded by Novartis; PARAGON-HF ClinicalTrials.gov number, NCT01920711.).


Asunto(s)
Aminobutiratos/administración & dosificación , Antagonistas de Receptores de Angiotensina/administración & dosificación , Enfermedades Cardiovasculares/mortalidad , Insuficiencia Cardíaca/tratamiento farmacológico , Hospitalización/estadística & datos numéricos , Neprilisina/antagonistas & inhibidores , Tetrazoles/administración & dosificación , Valsartán/administración & dosificación , Anciano , Aminobutiratos/efectos adversos , Angioedema/inducido químicamente , Antagonistas de Receptores de Angiotensina/efectos adversos , Método Doble Ciego , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/fisiopatología , Humanos , Hipotensión/inducido químicamente , Masculino , Persona de Mediana Edad , Calidad de Vida , Factores Sexuales , Método Simple Ciego , Volumen Sistólico , Tetrazoles/efectos adversos , Valsartán/efectos adversos
6.
Lancet ; 394(10205): 1254-1263, 2019 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-31447116

RESUMEN

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.


Asunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Antagonistas Adrenérgicos beta/uso terapéutico , Anciano , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Femenino , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Estudios Prospectivos , Factores Sexuales , Volumen Sistólico/efectos de los fármacos
7.
Rev Med Chil ; 147(3): 330-333, 2019 Mar.
Artículo en Español | MEDLINE | ID: mdl-31344170

RESUMEN

BACKGROUND: Pharmacological treatment improves survival in patients with heart failure with reduced ejection fraction. The use of sacubutril/valsartan and ivabradine has been recently approved and incorporated in the latest guidelines. AIM: To identify candidates eligible for these therapies among patients treated in a heart failure clinic, considering the inclusion criteria for the PARADIGM-HF and SHIFT trials. MATERIAL AND METHODS: Cross-sectional study on 158 patients aged 62 ± 11 years (67% male) with heart failure and reduced ejection fraction, with at least three months of follow-up and without decompensation. The percentage of patients complying for the inclusion criteria for the PARADIGM-HF y SHIFT trials was determined. RESULTS: In 37%, the etiology of heart failure was ischemic, 49% were in functional class I, their ejection fraction was 33 ± 11% and their median Pro-brain natriuretic peptide was 800 pg/mL. Ninety five percent were treated with vasodilators, 97% with beta-blockers and 82% with aldosterone antagonists. Using PARADIGM-HF and SHIFT criteria, 11 patients (7%) were eligible for sacubitril / valsartan and 21 patients (13.3%) for ivabradine. Among the main causes of non-eligibility for sacubitril / valsartan were being functional class I (48.7%) and not achieving a stable dose of enalapril ≥ 20 mg / day or losartan ≥ 100 mg / day (24.7%). In the case of ivabradine, apart from those in functional class I, the absence of sinus rhythm and a heart rate < 70 / min when receiving a maximal tolerated dose of beta-blockers, were present in 22%. CONCLUSIONS: A low percentage of our patients were eligible for these therapies. Among the causes that explain these results were clinical stability, a high percentage of patients in functional class I and being in a disease modifying treatment.


Asunto(s)
Aminobutiratos/administración & dosificación , Antagonistas de Receptores de Angiotensina/administración & dosificación , Fármacos Cardiovasculares/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Ivabradina/administración & dosificación , Tetrazoles/administración & dosificación , Anciano , Estudios Transversales , Relación Dosis-Respuesta a Droga , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente
9.
Basic Clin Pharmacol Toxicol ; 125(4): 345-352, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31058419

RESUMEN

The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open-label, three-period, fixed-sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9 days each. The pharmacokinetics of amlodipine, losartan and EXP-3174, an active metabolite of losartan, were assessed at steady-state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady-state (AUCτ , 165.15 ng h/mL [amlodipine alone] vs 172.36 ng h/mL [combination], P = 0.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954-1.178)]. In addition, the exposure of EXP-3174 was not affected by amlodipine (AUCτ , 1159.46 ng h/mL vs 1105.10 ng h/mL, P = 0.295) (GMR [90% CI], 0.957 [0.891-1.027]). However, amlodipine significantly decreased the exposure of losartan at steady-state (AUCτ , 1241.50 ng h/mL vs 1082.02 ng h/mL, P = 0.006) (GMR [90% CI], 0.875 [0.813-0.942]) and increased oral clearance of losartan (84.65 L/h vs 97.26 L/h, P = 0.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co-administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.


Asunto(s)
Amlodipino/farmacocinética , Antihipertensivos/farmacocinética , Hemodinámica/efectos de los fármacos , Losartán/farmacocinética , Administración Oral , Adulto , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/farmacocinética , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/efectos adversos , Bloqueadores de los Canales de Calcio/farmacocinética , Interacciones Farmacológicas , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Voluntarios Sanos , Humanos , Hipertensión/tratamiento farmacológico , Losartán/administración & dosificación , Losartán/efectos adversos , Masculino , Persona de Mediana Edad , República de Corea , Adulto Joven
10.
PLoS One ; 14(5): e0215604, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31050669

RESUMEN

AIM: Although the atheroprotective effects of statins and angiotensin II receptor blockers (ARBs) are well-established, little is known about their additive effects, especially during the early period of atherosclerosis. The aim of this study was to investigate whether combination of a statin and an ARB exerts synergistic anti-atherosclerotic effects, and to elucidate the mechanisms of combined effects. METHODS: Atherosclerotic plaques were developed in arteries of 23 rabbits using a high-cholesterol diet (HCD) and intra-arterial balloon inflation. Rabbits received one of five different treatment strategies for 4 weeks: positive control [n = 5, HCD]; negative control [n = 3, regular chow diet]; statin [n = 5, HCD and rosuvastatin 10 mg]; ARB [n = 5, HCD and olmesartan 20 mg]; and combination [n = 5, HCD and statin+ARB]. RESULTS: Histological analysis demonstrated that development of atherosclerotic plaques was inhibited more in combination group than in statin group (P = 0.001). Although macrophage infiltration identified by RAM11 staining was not significantly different between combination and individual treatment groups (31.76±4.84% [combination] vs. 38.11±6.53% [statin; P = 0.35] or 35.14±2.87% [ARB; P = 0.62]), the relative proportion of pro-inflammatory M1-macrophages was significantly lower in combination group than in ARB group (3.20±0.47% vs. 5.20±0.78%, P = 0.02). Furthermore, M2-macrophage polarization was higher in combination group than in statin group (17.70±3.04% vs. 7.86±0.68%, P = 0.001). CONCLUSION: Combination treatment with a statin and an ARB produced synergistic protective effects for atherosclerosis initiation and progression, which may be attributed to modulation of macrophage characteristics in the early period of atherosclerosis.


Asunto(s)
Antagonistas de Receptores de Angiotensina/administración & dosificación , Aterosclerosis/tratamiento farmacológico , Imidazoles/administración & dosificación , Rosuvastatina Cálcica/administración & dosificación , Tetrazoles/administración & dosificación , Antagonistas de Receptores de Angiotensina/farmacología , Animales , Aterosclerosis/inmunología , Aterosclerosis/prevención & control , Polaridad Celular , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Imidazoles/farmacología , Macrófagos/metabolismo , Masculino , Ratones , Células RAW 264.7 , Conejos , Rosuvastatina Cálcica/farmacología , Tetrazoles/farmacología , Resultado del Tratamiento
11.
Drugs Aging ; 36(7): 667-674, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-30949984

RESUMEN

BACKGROUND: The use of renin-angiotensin-aldosterone system inhibitors has increased over the past few years. There are conflicting data as to their relationship with acute kidney injury following surgery. OBJECTIVES: The objective of the article was to evaluate the risk of acute kidney injury in diabetic older patients treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and their medical outcomes following fragility hip fracture surgery. METHODS: Consecutive diabetic patients presenting with fragility hip fractures to our primary trauma center between January 2012 and June 2016 were included. Demographic and clinical data, including co-morbidities, medication use, and laboratory results, were collected from the electronic medical records. The primary outcome was the incidence of acute kidney injury; the secondary outcome was 1-year mortality. RESULTS: Two hundred and seventeen patients were included; 125 were receiving treatment with medications targeting the renin-angiotensin-aldosterone system. Demographic and clinical characteristics were similar between groups. No association was found between the use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and the risk of acute kidney injury, which occurred in 25% of the cohort. Univariate analysis revealed that diuretic use, particularly furosemide, increased the risk of acute kidney injury during hospitalization (p = 0.003). However, in a multivariate analysis, only age and estimated glomerular filtration rates were associated with an increased risk of acute kidney injury. Patients with acute kidney injury were found to have increased mortality during the first post-operative year (p < 0.001). CONCLUSIONS: Acute kidney injury is a frequent complication after hip fracture surgery in elderly diabetic patients and is associated with increased 1-year mortality; however, it was not found to be associated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker pre-fracture treatment.


Asunto(s)
Lesión Renal Aguda/etiología , Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Diabetes Mellitus/tratamiento farmacológico , Fracturas de Cadera/cirugía , Lesión Renal Aguda/inducido químicamente , Factores de Edad , Anciano de 80 o más Años , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Angiotensinógeno , Estudios de Cohortes , Diabetes Mellitus/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Incidencia , Masculino , Sistema Renina-Angiotensina/efectos de los fármacos , Estudios Retrospectivos
12.
Trials ; 20(1): 160, 2019 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-30836981

RESUMEN

BACKGROUND: Chronic treatment of hypertension or heart failure very often includes an angiotensin-converting enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) as renin-angiotensin system inhibitors (RASi) treatments. To stop or not to stop these medications before major surgery remains an unresolved issue. The lack of evidence leads to conflicting guidelines with respect to RASi management before major surgery. The purpose of this study is to evaluate the impact of a strategy of RASi continuation or discontinuation on perioperative complications in patients undergoing major non-cardiac surgery. METHODS: This is a multicenter, open-labeled randomized controlled trial in > 30 French centers. In the experimental group, RASi will be continued while the treatment will be stopped 48 h before the surgery in the control arm. The primary endpoint is a composite endpoint of major complications after surgery. An endpoint adjudication committee will review clinical data and adjudicate efficacy endpoints while blinded to the assigned study drug group. Main analysis will be by intention-to-treat comparing the composite outcome measure at 28 days in the two groups. A total of 2222 patients are planned to detect an absolute complications difference of 5%. DISCUSSION: The results of the trial should provide robust evidence to anesthesiologists and surgeons regarding management of RASi before major non-cardiac surgery. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03374449 . Registered on 11 December 2017.


Asunto(s)
Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Hipertensión/tratamiento farmacológico , Atención Perioperativa/métodos , Sistema Renina-Angiotensina/efectos de los fármacos , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Esquema de Medicación , Francia , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Estudios Multicéntricos como Asunto , Atención Perioperativa/efectos adversos , Complicaciones Posoperatorias/etiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
13.
J Am Coll Cardiol ; 73(11): 1273-1284, 2019 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-30898202

RESUMEN

BACKGROUND: With sacubitril/valsartan treatment, B-type natriuretic peptide (BNP) concentrations increase; it remains unclear whether change in BNP concentrations is similar across all assays for its measurement. Effects of sacubitril/valsartan on atrial natriuretic peptide (ANP) concentrations in patients are unknown. Lastly, the impact of neprilysin inhibition on mid-regional pro-ANP (MR-proANP), N-terminal pro-BNP (NT-proBNP), proBNP1-108, or C-type natriuretic peptide (CNP) is not well understood. OBJECTIVES: This study sought to examine the effects of sacubitril/valsartan on results from different natriuretic peptide assays. METHODS: Twenty-three consecutive stable patients with heart failure and reduced ejection fraction were initiated and titrated on sacubitril/valsartan. Change in ANP, MR-proANP, BNP (using 5 assays), NT-proBNP (3 assays), proBNP1-108, and CNP were measured over 3 visits. RESULTS: Average time to 3 follow-up visits was 22, 46, and 84 days. ANP rapidly and substantially increased with initiation and titration of sacubitril/valsartan, more than doubling by the first follow-up visit (+105.8%). Magnitude of ANP increase was greatest in those with concentrations above the median at baseline (+188%) compared with those with lower baseline concentrations (+44%); ANP increases were sustained. Treatment with sacubitril/valsartan led to inconsistent changes in BNP, which varied across methods assessed. Concentrations of MR-proANP, NT-proBNP, and proBNP1-108 variably declined after treatment; whereas CNP concentrations showed no consistent change. CONCLUSIONS: Initiation and titration of sacubitril/valsartan led to variable changes in concentrations of multiple natriuretic peptides. These results provide important insights into the effects of sacubitril/valsartan treatment on individual patient results, and further suggest the benefit of neprilysin inhibition may be partially mediated by increased ANP concentrations.


Asunto(s)
Aminobutiratos , Insuficiencia Cardíaca , Péptido Natriurético Encefálico , Neprilisina , Tetrazoles , Aminobutiratos/administración & dosificación , Aminobutiratos/farmacocinética , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/farmacocinética , Monitoreo de Drogas/métodos , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/análisis , Péptido Natriurético Encefálico/sangre , Neprilisina/antagonistas & inhibidores , Neprilisina/metabolismo , Fenómenos Farmacológicos , Volumen Sistólico , Tetrazoles/administración & dosificación , Tetrazoles/farmacocinética
14.
PLoS One ; 14(2): e0212907, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30817783

RESUMEN

BACKGROUND: Current heart failure (HF) guidelines recommend titrating angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) and beta-blockers (BBs) to target doses used in pivotal placebo-controlled randomized controlled trials (RCTs). Despite a number of RCTs comparing different doses (i.e. higher versus lower doses) of ACEIs, ARBs and BBs, the effects of higher versus lower doses on efficacy and safety remains unclear. For this reason, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of higher versus lower doses of ACEIs, ARBs and BBs in patients with HFrEF. METHODS: We searched MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) via Ovid from inception to April 25th, 2018 and opentrials.net and clinicaltrials.gov for relevant trials that compared different doses of medications in heart failure. We analyzed trials by drug class (ACEIs, ARBs, and BBs) for efficacy outcomes (all-cause mortality, cardiovascular mortality, all-cause hospitalizations, HF hospitalizations, HF worsening). For safety outcomes, we pooled trials within and across drug classes. RESULTS: Our meta-analysis consisted of 14 RCTs. Using GRADE criteria, the quality of evidence for ACEIs and ARBs was assessed as generally moderate for efficacy and high for adverse effects, whereas overall quality for BBs was very low to low. Over ~2-4 years higher versus lower doses of ACEIs, ARBs or BBs did not significantly reduce all-cause mortality [ACEIs relative risk (RR) 0.94 (95% confidence interval 0.87-1.02)], ARBs RR 0.96 (0.87-1.04), BBs RR 0.25 (0.06-1.01)] or all cause hospitalizations [ACEIs relative risk (RR) 0.94 (95% confidence interval 0.86-1.02)], ARBs RR 0.98 (0.93-1.04), BBs RR 0.93 (0.39-2.24)]. However, all point estimates favoured higher doses. Higher doses of ARBs significantly reduced hospitalization for HF [RR 0.89 (0.80-0.99)- 2.8% ARR], and higher doses of ACEIs and ARBs significantly reduced HF worsening [RR 0.85 (0.79-0.92)- 5.1% ARR and 0.91 (0.84-0.99)- 3.2% ARR, respectively] compared to lower doses. None of the differences between higher versus lower doses of BBs were significant; however, precision was low. Higher doses of these medications compared to lower doses increased the risk of discontinuation due to adverse events, hypotension, dizziness, and for ACEIs and ARBs, increased hyperkalemia and elevations in serum creatinine. Absolute increase in harms for adverse effects ranged from ~ 3 to 14%. CONCLUSIONS: Higher doses of ACEIs and ARBs reduce the risk of HF worsening compared to lower doses, and higher doses of ARBs also reduce the risk of HF hospitalization but the evidence is sparse and imprecise. Higher doses increase the chance of adverse effects compared to lower doses. Evidence for BBs is inconclusive. These results support initially always starting at low doses of ACEIs/ARBs and only titrating the dose up if the patient tolerates dose increases.


Asunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Antagonistas Adrenérgicos beta/efectos adversos , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Seguridad , Volumen Sistólico , Resultado del Tratamiento
15.
Am J Cardiovasc Drugs ; 19(3): 259-286, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30737754

RESUMEN

INTRODUCTION: Current guidelines recommend renin-angiotensin-aldosterone system (RAAS) inhibitors in the treatment of diabetic kidney disease (DKD). However, evidence suggests that the combined use of RAAS blockers may be associated with increased rates of adverse events. OBJECTIVES: Our objective was to examine the efficacy and safety of dual blockade of the RAAS in patients with DKD. METHODS: This was a systematic review and meta-analysis of randomized controlled trials (RCTs) published between January 1990 and January 2018 sourced via the PubMed, EMBASE, and Cochrane Library databases. RCTs were included if they investigated the efficacy and safety of dual blockade therapy compared with monotherapy in patients with DKD. Random effects models were used in meta-analysis to account for heterogeneities in effect sizes across the reviewed studies. Analyses were stratified by blood pressure and albuminuria. We further conducted subgroup analyses by considering various combinations of RAAS inhibitors. RESULTS: Based on 42 RCTs with 14,576 patients, dual RAAS blockade therapy was associated with significant decreases in blood pressure, albuminuria, and proteinuria. However, dual therapy was not superior to monotherapy in terms of reductions in all-cause mortality, cardiovascular mortality, or progression to end-stage renal disease (ESRD). Significant increases in serum potassium and rates of hyperkalemia and hypotension were more common in patients treated with dual therapy. However, glomerular filtration rates (GFR) did not decrease significantly with dual therapy. In subgroup analysis, an angiotensin-converting enzyme inhibitor (ACEI) plus an angiotensin-receptor blocker (ARB) or a direct renin inhibitor (DRI) plus an ACEI/ARB did not significantly increase the risk of hyperkalemia, hypotension, and adverse events, and the risk of hypotension increased significantly within the normotensive subgroup but not within the hypertensive subgroup. The risk of hyperkalemia increased significantly in patients with DKD with macroalbuminuria but not in those with microalbuminuria. CONCLUSION: Dual inhibition therapy is superior to monotherapy for blood pressure control and urine protein reduction, though such superiority does not translate into improvements in longer-term outcomes, such as reduced progression to ESRD, all-cause mortality, and cardiovascular mortality. An ACEI plus an ARB or a DRI plus an ACEI/ARB may be a safe and effective therapy for patients with DKD, and combination therapy may be suitable for patients with DKD and hypertension and microalbuminuria.


Asunto(s)
Nefropatías Diabéticas/tratamiento farmacológico , Sistema Renina-Angiotensina/efectos de los fármacos , Renina/antagonistas & inhibidores , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/efectos adversos , Antagonistas de Receptores de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Presión Sanguínea/efectos de los fármacos , Nefropatías Diabéticas/fisiopatología , Progresión de la Enfermedad , Quimioterapia Combinada , Humanos , Guías de Práctica Clínica como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto
16.
Eur J Heart Fail ; 21(3): 337-341, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30741494

RESUMEN

AIMS: To assess differences in diuretic dose requirements in patients treated with sacubitril/valsartan compared with enalapril in the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure (PARADIGM-HF) trial. METHODS AND RESULTS: Overall, 8399 patients with New York Heart Association class II-IV heart failure and reduced LVEF were randomized to sacubitril/valsartan 200 mg bid or enalapril 10 mg twice daily. Loop diuretic doses were assessed at baseline, 6, 12, and 24 months, and furosemide dose equivalents were calculated via multiplication factors (2x for torsemide and 40x for bumetanide). Percentages of participants with reductions or increases in loop diuretic dose were determined. At baseline, 80.8% of participants were taking any diuretics (n = 6290 for loop diuretics, n = 496 for other diuretics); of those, recorded dosage data for loop diuretics were available on 5487 participants. Mean baseline furosemide equivalent doses were 48.2 mg for sacubitril/valsartan and 49.6 mg for enalapril (P = 0.25). Patients treated with sacubitril/valsartan were more likely to reduce diuretic dose and less likely to increase diuretic dose relative to those randomized to enalapril at 6, 12, 24 months post-randomization, with an overall decreased diuretic use of 2.0% (P = 0.02), 4.1% (P < 0.001), and 6.1% (P < 0.001) at 6, 12, and 24 months, respectively, with similar findings in an on-treatment analysis. CONCLUSION: Treatment with sacubitril/valsartan was associated with more loop diuretic dose reductions and fewer dose increases compared with enalapril, suggesting that treatment with sacubitril/valsartan may reduce the requirement for loop diuretics relative to enalapril in patients with heart failure with reduced ejection fraction.


Asunto(s)
Aminobutiratos , Enalapril , Furosemida , Insuficiencia Cardíaca , Volumen Sistólico , Tetrazoles , Anciano , Aminobutiratos/administración & dosificación , Aminobutiratos/farmacocinética , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/farmacocinética , Disponibilidad Biológica , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas/métodos , Monitoreo de Drogas/estadística & datos numéricos , Enalapril/administración & dosificación , Enalapril/farmacocinética , Femenino , Furosemida/administración & dosificación , Furosemida/farmacocinética , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Administración del Tratamiento Farmacológico/estadística & datos numéricos , Persona de Mediana Edad , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/administración & dosificación , Inhibidores del Simportador de Cloruro Sódico y Cloruro Potásico/farmacocinética , Tetrazoles/administración & dosificación , Tetrazoles/farmacocinética
17.
JAMA Cardiol ; 4(3): 195-196, 2019 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-30810709
18.
JACC Heart Fail ; 7(4): 350-358, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30738978

RESUMEN

OBJECTIVES: This study sought to determine the rate of use of target doses of foundational guideline-directed medical therapy (GDMT) in a contemporary cohort of patients with heart failure with reduced ejection fraction (HFrEF) across systolic blood pressure (SBP) categories. BACKGROUND: Patients with HFrEF are infrequently titrated to recommended doses of GDMT. The relationship between SBP and achieving GDMT target doses is not well studied. METHODS: Patients enrolled in the CHAMP-HF (Change the Management of Patients With Heart Failure) registry without documented intolerance to angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors (ARNIs), and beta blockers (BBs) were assessed at enrollment. We estimated the proportion receiving target doses (% of target dose [95% confidence interval (CI)]) based on the most recent American College of Cardiology/American Heart Association/Heart Failure Society of America heart failure guidelines at baseline in all patients, and by SBP category (≥110 vs. <110 mm Hg). RESULTS: Of the 3,095 patients eligible for analysis, 2,421 (78.2%) had SBP ≥110 mm Hg. The proportion of patients receiving target doses were 18.7% (95% CI: 17.3% to 20.0%; BB), 10.8% (95% CI: 9.7% to 11.9%; ACEI/ARB), and 2.0% (95% CI: 1.5% to 2.5%; ARNI). Among those with SBP <110 mm Hg (n = 674), 17.5% (95% CI: 14.6% to 20.4%; BB), 6.2% (95% CI: 4.4% to 8.1%; ACEI/ARB), and 1.8% (95% CI: 0.8% to 2.8%; ARNI) were receiving target doses. Among those with SBP ≥110 mm Hg (n = 2,421), 19.0% (95% CI: 17.4% to 20.6%; BB), 12.1% (95% CI: 10.8% to 13.4%; ACEI/ARB), and 2.0% (95% CI: 1.5% to 2.6%; ARNI) were receiving target doses. CONCLUSIONS: In a large, contemporary registry of outpatients with chronic HFrEF eligible for treatment with BBs and ACEI/ARB/ARNI, <20% of patients were receiving target doses, even among those with SBP ≥110 mm Hg.


Asunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas de Receptores de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Sistema de Registros , Volumen Sistólico/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Presión Sanguínea/fisiología , Estudios Transversales , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/fisiopatología , Hospitalización/tendencias , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
19.
Ir J Med Sci ; 188(4): 1169-1174, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30796605

RESUMEN

INTRODUCTION: Sacubitril-valsartan has been shown by the PARADIGM-HF trial to decrease hospital admissions and improve mortality in patients with heart failure with reduced ejection fraction. The PARADIGM trial had stringent exclusion criteria. It is not known how applicable these trial criteria are to real-life practice. In this study, we sought to determine the percentage of patients eligible for sacubitril-valsartan therapy in a level 3 hospital without a dedicated heart failure service. METHODS: All patients discharged from our service with a diagnosis of congestive cardiac using our hospital in-patient enquiry (HIPE) system underwent hierarchal analysis. In order to be deemed eligible for sacubitril-valsartan therapy, patients had to meet PARADIGM-HF inclusion criteria. RESULTS: Our 143 patients represented a more clinically unwell, elderly cohort than the PARADIGM trial study population. Only 24 patients (16.66%) had an ejection fraction of 40% or less. Our results indicate that only 4/143 patients in a real-world setting (2.79%) were eligible for sacubitril-valsartan therapy at the point of discharge as per the PARADIGM-HF study criteria. This is primarily due to the higher than expected percentage of patients in our cohort with an ejection fraction of over 40% (n = 120) and the low percentage of patients on therapeutic doses of ACEI/ARB (n = 15). CONCLUSIONS: Our study showed that a smaller than expected proportion of our patients in real-world practice are suitable for sacubitril-valsartan therapy at discharge. Most patients were in the HFPEF cohort which does not currently have evidence for treatment with sacubitril-valsartan. Low rates of prescribing of basic heart failure medicatons and the absence of dedicated heart failure services in a non-tertiary centre may explain the poor compliance observed. Improving guideline adherence and increasing awareness of evidence-based medication use at primary and secondary care levels would be of benefit to Irish heart failure patients.


Asunto(s)
Aminobutiratos/administración & dosificación , Antagonistas de Receptores de Angiotensina/administración & dosificación , Insuficiencia Cardíaca/tratamiento farmacológico , Tetrazoles/administración & dosificación , Anciano , Anciano de 80 o más Años , Insuficiencia Cardíaca/mortalidad , Hospitalización/estadística & datos numéricos , Humanos , Alta del Paciente , Estudios Retrospectivos , Volumen Sistólico , Resultado del Tratamiento
20.
Curr Hypertens Rep ; 21(1): 5, 2019 01 18.
Artículo en Inglés | MEDLINE | ID: mdl-30659374

RESUMEN

PURPOSE OF REVIEW: Hypertension and antihypertensive drug utilization are remarkably prevalent in ESRD patients. Management of blood pressure elevation in this population is complicated by many factors, including a multidimensional etiology, challenges in obtaining accurate and appropriately timed blood pressure measurements, highly specific drug dosing requirements, and a paucity of outcomes-based evidence to guide management decisions. The purpose of this review is to summarize and apply knowledge from existing clinical trials to enhance safe and effective use of antihypertensive agents in dialysis patients. RECENT FINDINGS: Two meta-analyses have established the benefit of antihypertensive therapy in ESRD. Data supporting the use of one antihypertensive class over another is less robust; however, beta-blockers have more clearly demonstrated improved cardiovascular outcomes in prospective randomized trials. Interdialytic home blood pressure monitoring has been demonstrated to be better associated with cardiovascular outcomes than clinic pre- or post-dialysis readings and should ideally be considered as a routine part of blood pressure management in this population. As data from small trials provides limited guidance for the management of hypertension in ESRD, more research is needed to guide medication selection and utilization. Specifically, large prospective randomized trails comparing cardiovascular outcomes of various medication classes and differing blood pressure targets are needed.


Asunto(s)
Antihipertensivos/administración & dosificación , Hipertensión/tratamiento farmacológico , Fallo Renal Crónico/terapia , Diálisis Renal , Antagonistas de Receptores Adrenérgicos alfa 2/administración & dosificación , Antagonistas de Receptores Adrenérgicos alfa 2/farmacocinética , Antagonistas Adrenérgicos beta/administración & dosificación , Antagonistas Adrenérgicos beta/farmacocinética , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antagonistas de Receptores de Angiotensina/farmacocinética , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Antihipertensivos/farmacocinética , Determinación de la Presión Sanguínea , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/farmacocinética , Relación Dosis-Respuesta a Droga , Humanos , Hipertensión/complicaciones , Fallo Renal Crónico/complicaciones , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Antagonistas de Receptores de Mineralocorticoides/farmacocinética , Vasodilatadores/administración & dosificación , Vasodilatadores/farmacocinética
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