RESUMO
BACKGROUND: Left ventricular (LV) hypertrophy, a marker of cardiac end-organ damage, is associated with an increased risk of cardiovascular morbidity and mortality. Inhibitors of the renin-angiotensin-aldosterone system may reduce LV mass to a greater extent than other antihypertensive agents. We compared the effect of aliskiren, the first orally active direct renin inhibitor, the angiotensin-receptor blocker losartan, and their combination on the reduction of LV mass in hypertensive patients. METHODS AND RESULTS: We randomized 465 patients with hypertension, increased ventricular wall thickness, and body mass index >25 kg/m(2) to receive aliskiren 300 mg, losartan 100 mg, or their combination daily for 9 months. Patients were treated to standard blood pressure targets with add-on therapy, excluding other inhibitors of the renin-angiotensin-aldosterone system and beta-blockers. Patients underwent cardiovascular magnetic resonance imaging for assessment of LV mass at baseline and at study completion. The primary objective was to compare change in LV mass index from baseline to follow-up in the combination and losartan arms; the secondary objective was to determine whether aliskiren was noninferior to losartan in reducing LV mass index from baseline to follow-up. Systolic and diastolic blood pressures were reduced similarly in all treatment groups (6.5+/-14.9/3.8+/-10.1 mm Hg in the aliskiren group; 5.5+/-15.6/3.7+/-10.7 mm Hg in the losartan group; 6.6+/-16.6/4.6+/-10.5 mm Hg in the combination arm; P<0.0001 within groups, P=0.81 between groups). LV mass index was reduced significantly from baseline in all treatment groups (4.9-, 4.8-, and 5.8 g/m(2) reductions in the aliskiren, losartan, and combination arms, respectively; P<0.0001 for all treatment groups). The reduction in LV mass index in the combination group was not significantly different from that with losartan alone (P=0.52). Aliskiren was as effective as losartan in reducing LV mass index (P<0.0001 for noninferiority). Safety and tolerability were similar across all treatment groups. CONCLUSIONS: Aliskiren was as effective as losartan in promoting LV mass regression. Reduction in LV mass with the combination of aliskiren plus losartan was not significantly different from that with losartan monotherapy, independent of blood pressure lowering. These findings suggest that aliskiren was as effective as an angiotensin receptor blocker in attenuating this measure of myocardial end-organ damage in hypertensive patients with LV hypertrophy.
Assuntos
Amidas/administração & dosagem , Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Fumaratos/administração & dosagem , Hipertensão/tratamento farmacológico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Losartan/administração & dosagem , Idoso , Amidas/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Ecocardiografia , Feminino , Fumaratos/efeitos adversos , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/patologia , Losartan/efeitos adversos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Comfort warming systems aim to produce a comfortable local environment over which the individual patient has control. We studied a patient-adjustable comfort warming system using the Bair PAWS (Patient Adjustable Warming System) (Arizant Healthcare, Inc, Eden Prairie, MN), specifically to study comfort warming rather than therapeutic warming. One-hundred thirty patients were enrolled in this prospective randomized clinical trial, with 58 patients randomized to the patient warming gown, and 72 randomized to the warm blanket group. Groups were similar for gender, age, height, weight, surgical time, body surface area, and body mass index. The patient-adjustable warming system group had perceived greater control and satisfaction at 30 minutes after treatment was initiated compared with the warmed blanket control group. However, there were no differences in satisfaction levels with thermal comfort among those patients contacted one day postoperatively. Additional research is needed to improve external validity of study findings. Further refinement of a nursing definition of thermal comfort should be explored.
Assuntos
Ansiedade , Regulação da Temperatura Corporal , Satisfação do Paciente , Procedimentos Cirúrgicos Operatórios , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
INTRODUCTION: In Chiari I patients, postoperative pain and discomfort frequently slow the transition back to the home setting. OBJECTIVE: We sought to determine the effect of standardized ketamine infusion protocols on hospital length of stay (LOS). METHODS: This retrospective cohort study reviewed 100 consecutive adult patients undergoing Chiari I decompression. Fifty-nine patients were placed on a 2-3 mg/hr ketamine drip until postoperative day 1. This group was compared with a group who received 2-3 mg/hr of ketamine until postoperative day 2 (19 patients) and patients who did not receive ketamine at all (22 patients). Clinical characteristics, opioid use, LOS, and relative hospitalization costs were assessed. All narcotic amounts were converted into milligram equivalents of morphine. RESULTS: LOS of the short-ketamine group was 46.5 hours when compared with the long-ketamine group (66.8 hours) and no-ketamine group (56.9 hours). There was a statistically significant difference when comparing the short-ketamine group with the long-ketamine group and no-ketamine group together (P < 0.001), as well as when compared individually (P = 0.001 and 0.004). The mean cost of hospitalization was 20% less when a short-ketamine protocol was used (P < 0.001). Mean morphine milligram equivalents used postoperatively were 148 mg in the short-ketamine group, 196 mg in the long-ketamine group, and 187 mg in the no-ketamine group (P = 0.65). No adverse events from ketamine were noted. CONCLUSIONS: Ketamine at subanesthetic levels may be an effective tool to facilitate early return home postoperatively and may significantly reduce medical costs.
Assuntos
Analgésicos/administração & dosagem , Malformação de Arnold-Chiari/cirurgia , Análise Custo-Benefício , Ketamina/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Adulto , Analgésicos/economia , Malformação de Arnold-Chiari/economia , Protocolos Clínicos , Feminino , Custos de Cuidados de Saúde , Humanos , Ketamina/economia , Tempo de Internação/economia , Masculino , Dor Pós-Operatória/economia , Melhoria de Qualidade , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
AIMS: We evaluated the influence of concomitant mineralocorticoid receptor antagonists (MRAs) on the safety and neurohumoral effects of a direct renin inhibitor in the ALiskiren Observation of Heart Failure Treatment (ALOFT) study. METHODS AND RESULTS: Patients with stable New York Heart Association class II-IV heart failure (HF), plasma B-type natriuretic peptide (BNP) concentration >100 pg/mL, and treated with an angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker) and ß-blocker were randomized to once-daily, double-blind treatment with aliskiren 150 mg or placebo, added to optimal HF therapy, for 12 weeks. Safety, tolerability, and effects of aliskiren on neurohumoral biomarkers were assessed in patients who received (MRA+) and did not receive (MRA-) MRA treatment at baseline. Of the 302 randomized patients, 101 were receiving MRA treatment (aliskiren, n = 52; placebo, n = 49). Mineralocorticoid receptor antagonist status did not affect the ability of aliskiren 150 mg, added to standard HF therapy, to lower BNP, N-terminal proBNP, plasma renin activity, and urinary aldosterone. For example, the end-of-study to baseline ratio of geometric mean for BNP was: MRA+ group: aliskiren 0.68 [95% confidence interval (CI) 0.47, 0.98], placebo 0.85 (0.58, 1.24); MRA- group: aliskiren 0.62 (0.45, 0.84), placebo 0.85 (0.63, 1.15), interaction P= 0.720. The incidence of pre-specified adverse events (renal dysfunction, symptomatic hypotension, and hyperkalaemia) was low, and there were no significant differences between aliskiren and placebo in either MRA subgroup. CONCLUSION: Aliskiren 150 mg added to standard HF therapy was well tolerated over 12 weeks and provided beneficial changes in neurohumoral biomarkers regardless of concomitant MRA treatment.
Assuntos
Amidas/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Fumaratos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Análise de Variância , 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 , Intervalos de Confiança , Feminino , Humanos , Masculino , Estatística como Assunto , Volume Sistólico , Função Ventricular EsquerdaRESUMO
BACKGROUND: High circulating aldosterone levels stimulate myocardial fibrosis and left ventricular hypertrophy (LVH). However, it is not clear whether suppression of aldosterone directly contributes to LVH regression in hypertensive patients. METHODS: The Aliskiren in Left Ventricular Hypertrophy (ALLAY) trial randomised 465 hypertensive overweight subjects with LVH to the direct renin inhibitor aliskiren 300 mg, losartan 100 mg or the combination and followed patients for 9 months. All patients were treated to standard blood pressure targets. Left ventricular (LV) mass index (LVMI) and LV wall thickness (LVWT) were assessed by cardiac magnetic resonance. A subset of 136 patients who had plasma aldosterone concentration (ALDO) measured at baseline and study end was analysed. RESULTS: At baseline, plasma ALDO was modestly related to systolic blood pressure, LVMI, and wall thickness (all, p < 0.05). Aliskiren, either alone or in combination, was associated with a significantly greater reduction from baseline to 9 months in plasma aldosterone than losartan alone (p < 0.02). Reduction in ALDO was related to reduction in LVMI even after adjustment for baseline ALDO, BP reduction and treatment group (p for trend = 0.042). CONCLUSION: In hypertensive patients with increased LVWT, aliskiren alone or in combination with the angiotensin receptor blocker losartan provides greater reduction in aldosterone compared to losartan alone. Moreover, suppression of aldosterone was associated with reduction of LVH, independently of the change in SBP, suggesting that suppression of aldosterone, a known mediator of LVH, may be particularly important for LVH regression and as a target for therapy.
Assuntos
Aldosterona/sangue , Hipertensão/sangue , Hipertensão/complicações , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/patologia , Amidas/administração & dosagem , Amidas/farmacologia , Amidas/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Demografia , Feminino , Fumaratos/administração & dosagem , Fumaratos/farmacologia , Fumaratos/uso terapêutico , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/fisiopatologia , Losartan/administração & dosagem , Losartan/farmacologia , Losartan/uso terapêutico , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/efeitos dos fármacos , Sístole/efeitos dos fármacosRESUMO
AIMS: To examine the relationships between baseline characteristics and urinary albumin excretion in the extensively phenotyped patients in the ALiskiren Observation of heart Failure Treatment (ALOFT) study. METHODS AND RESULTS: Urinary albumin creatinine ratio (UACR) was available in 190 of 302 (63%) patients randomized in ALOFT. Of these, 107 (56%) had normal albumin excretion, 63 (33%) microalbuminuria, and 20 (11%) macroalbuminuria. Compared with patients with normoalbuminuria, those with microalbuminuria had a greater prevalence of diabetes (48 vs. 26%, P = 0.005) and a lower estimated glomerular filtration rate (eGFR) (60.7 vs. 68.3 mL/min/1.73 m(2), P = 0.01). Patients with macroalbuminuria had additional differences from those with a normal UACR, including younger age (63 vs. 69 years, P = 0.02), higher glycated haemoglobin (HbA1c; 7.9 vs. 6.2%, P < 0.001), and different echocardiographic findings. Of the non-diabetic patients, 28% had microalbuminuria and 7% had macroalbuminuria. Independent predictors of UACR in these patients included N-terminal pro B-type natriuretic peptide (NT-proBNP), HbA1c, and left ventricular diastolic dimension. Increased UACR was not associated with markers of inflammation or of renin angiotensin aldosterone system activation and was not reduced by aliskiren. CONCLUSIONS: Increased UACR is common in patients with heart failure, including non-diabetics. Urinary albumin creatinine ratio is independently associated with HbA1c and NT-proBNP, even in non-diabetic patients.