Polifarmácia e cognição em pacientes com idade avançada / Polypharmacy and cognition in elderly patients

Objetivo: Avaliar a prevalência da polifarmácia e da prescrição de medicações inapropriadas, bem como suas associações com a capacidade cognitiva e funcional do idoso. Métodos: Estudo observacional transversal, no qual foram analisadas as medicações prescritas em 141 prontuários para pacientes acima de 50 anos, em associação com testes que quantificaram a capacidade funcional e cognitiva deles. Resultados: Observou-se média de 4,41 medicamentos por paciente, sendo que 0,41 deles foram considerados inapropriado, segundo o critério de Beers. Verificou-se também relação estatisticamente significativa quanto ao número de medicações e testes que mediam a capacidade funcional e cognitiva dos idosos. Conclusão: O aumento da polifarmácia e da prescrição de medicações potencialmente inadequadas acarretou significativa piora da capacidade cognitiva e funcional do idoso

Objective: To evaluate the prevalence of polypharmacy and of the prescription of inappropriate medications, as well as their associations with the cognitive and functional capacity of the elderly. Methods: Cross-sectional observational study which analyzed the drugs prescribed in 141 medical records for patients over 50 years of age, associated with tests that quantified their functional and cognitive capacity. Results: An average of 4.41 medications per patient was observed, and 0.41 were considered inappropriate according to the Beers criteria. There was also a statistically significant relation regarding the number of medications and tests that measure the functional and cognitive capacity of the elderly. Conclusion: The increase in polypharmacy and in the prescription of potentially inappropriate medications led to a significant impairment of the cognitive and functional capacity of the elderly

Prescripción de fármacos bloqueadores del sistema renina angiotensina en pacientes con enfermedad renal crónica etapa 3 en atención primaria de salud / Prescription of renin-angiotensin-aldosterone system blockers in patients with stage 3 chronic kidney disease

Background: To reduce the progression of chronic kidney disease (CKD) and cardiovascular risk, the guidelines recommend the blockade of the renin-angiotensin-aldosterone system (RAAS) in patients with proteinuria. Aim: To assess the frequency of enalapril or losartan use in diabetics or hypertensive patients with stage 3 CKD. Material and Methods: Review of clinical records of patients with CKD in an urban primary care clinic. Results: We identified 408 subjects aged 40 to 98 years (66% women) with stage 3 CKD. Sixty six percent had only hypertension and 34% were diabetic with or without hypertension. Seventy four percent received RAAS blockers (52% used enalapril, 45% losartan and 2% both medications). RAAS blockers were used in 70% of hypertensive and 78% of diabetic patients. The prescription in hypertensive diabetics with microalbuminuria was lower than in those without microalbuminuria (72% vs 87%, p < 0.05), but the opposite occurred in pure hypertensive patients with and without microalbuminuria (88% vs 69%, p < 0.05). There were no significant differences in blood pressure levels, microalbuminuria or serum potassium levels between RAAS blocker users and non-users. No differences were observed either between enalapril and losartan users. Conclusions: The adherence to clinical guidelines is insufficient and users of the recommended drugs did not achieve the expected goals.

Diuretics are Similar to Losartan on Echocardiographic Target-Organ Damage in Stage I Hypertension. PREVER-Treatment Study / Diuréticos são Similares à Losartana na Avaliação Ecocardiográfica de Lesão a Órgãos-Alvo no Estágio I da Hipertensão. Estudo PREVER-Treatment

Abstract Blood pressure (BP)-lowering therapy improves left ventricular (LV) parameters of hypertensive target-organ damage in stage II hypertension, but whether there is a drug-class difference in echocardiographic parameters in stage I hypertension patients is less often studied. In the PREVER treatment study, where individuals with stage I hypertension were randomized for treatment with diuretics (chlorthalidone/amiloride) or losartan, 110 participants accepted to participate in a sub-study, where two-dimensional echocardiograms were performed at baseline and after 18 months of antihypertensive treatment. As in the general study, systolic BP reduction was similar with diuretics or with losartan. Echocardiographic parameters showed small but significant changes in both treatment groups, with a favorable LV remodeling with antihypertensive treatment for 18 months when target blood pressure was achieved either with chlorthalidone/amiloride or with losartan as the initial treatment strategy. In conclusion, even in stage I hypertension, blood pressure reduction is associated with improvement in echocardiographic parameters, either with diuretics or losartan as first-drug regimens.

Resumo A terapia de redução da pressão arterial (PA) melhora os parâmetros do ventrículo esquerdo (VE) na lesão a órgãos-alvo causada pela condição hipertensiva na hipertensão de estágio II; no entanto, se existem ou não diferenças relacionadas à classe de medicamentos nos parâmetros ecocardiográficos de pacientes com hipertensão estágio I é menos frequentemente estudado. No estudo PREVER-treatment, em que indivíduos com hipertensão estágio I foram randomizados para tratamento com diuréticos (clortalidona/amilorida) ou losartana, 110 participantes aceitaram participar de um subestudo, no qual foram realizados ecocardiogramas bidimensionais basais e após 18 meses de tratamento anti-hipertensivo. Como no estudo geral, a redução da PA sistólica foi semelhante com diuréticos ou com losartana. Os parâmetros ecocardiográficos mostraram pequenas mas significativas alterações em ambos os grupos de tratamento, com um remodelamento favorável do VE com tratamento anti-hipertensivo por 18 meses, quando a pressão arterial alvo foi atingida com clortalidona/amilorida ou com losartana como estratégia inicial de tratamento. Em conclusão, mesmo na hipertensão estágio I, a redução da pressão arterial está associada à melhora nos parâmetros ecocardiográficos tanto com o uso de diuréticos ou losartana como primeiro esquema de tratamento farmacológico.

Farmácia Popular Program: pharmaceutical market analysis of antihypertensive acting on the renin-angiotensin system medicines / Programa Farmácia Popular: análise do mercado farmacêutico de anti-hipertensivos do sistema renina-angiotensina

Abstract This paper aims to analyse changes in the retail pharmaceutical market following policy changes in the Farmácia Popular Program (FP), a medicines subsidy program in Brazil. The retrospective longitudinal analyses focus on therapeutic class of agents acting on the renin-angiotensin system. Data obtained from QuintilesIMS (formerly IMS Health) included private retail pharmacy sales volume (pharmaceutical units) and sales values from 2002 to 2013. Analyses evaluated changes in market share following key FP policy changes. The therapeutic class was selected due to its relevance to hypertension treatment. Market share was analysed by therapeutic sub-classes and by individual company. Losartan as a single product accounted for the highest market share among angiotensin II antagonists. National companies had higher sales volume during the study period, while multinational companies had higher sales value. Changes in pharmaceutical market share coincided with the inclusion of specific products in the list of medicines covered by FP and with increases in or exemption from patient copayment.

Resumo Este artigo visa analisar as mudanças no mercado de varejo farmacêutico, seguindo as alterações de diretiva no Programa Farmácia Popular (FP), que realiza subvenção de medicamentos no Brasil, em parceria pública privada. Foi realizada análise longitudinal retrospectiva dos medicamentos da classe terapêutica dos agentes que atuam sobre o sistema renina-angiotensina. Os dados obtidos do QuintilesIMS incluíram o varejo farmacêutico em termos do volume e valores de vendas de 2002 a 2013. Análises realizadas consideraram intervenções e reformas ocorridas no FP e seu impacto no mercado farmacêutico da classe terapêutica selecionada, devido a sua relevância para o tratamento da hipertensão. Também se examinou o comportamento do mercado tomando por base as empresas farmacêuticas produtoras. Losartan monodroga representou a maior fatia de mercado entre os antagonistas de angiotensina II. Empresas nacionais obtiveram maior volume de vendas durante o período de estudo, enquanto as empresas multinacionais exibiram maior valor de vendas. Mudanças no mercado farmacêutico coincidiram com a inclusão de produtos específicos na lista de medicamentos abrangidos pelo FP e com aumentos ou isenção de copagamento pelos pacientes.

Short-term add-on therapy with angiotensin receptor blocker for end-stage inotrope-dependent heart failure patients: B-type natriuretic peptide reduction in a randomized clinical trial

OBJECTIVE: We aimed to evaluate angiotensin receptor blocker add-on therapy in patients with low cardiac output during decompensated heart failure. METHODS: We selected patients with decompensated heart failure, low cardiac output, dobutamine dependence, and an ejection fraction <0.45 who were receiving an angiotensin-converting enzyme inhibitor. The patients were randomized to losartan or placebo and underwent invasive hemodynamic and B-type natriuretic peptide measurements at baseline and on the seventh day after intervention. ClinicalTrials.gov: NCT01857999. RESULTS: We studied 10 patients in the losartan group and 11 patients in the placebo group. The patient characteristics were as follows: age 52.7 years, ejection fraction 21.3%, dobutamine infusion 8.5 mcg/kg.min, indexed systemic vascular resistance 1918.0 dynes.sec/cm5.m2, cardiac index 2.8 L/min.m2, and B-type natriuretic peptide 1,403 pg/mL. After 7 days of intervention, there was a 37.4% reduction in the B-type natriuretic peptide levels in the losartan group compared with an 11.9% increase in the placebo group (mean difference, -49.1%; 95% confidence interval: -88.1 to -9.8%, p = 0.018). No significant difference was observed in the hemodynamic measurements. CONCLUSION: Short-term add-on therapy with losartan reduced B-type natriuretic peptide levels in patients hospitalized for decompensated severe heart failure and low cardiac output with inotrope dependence. .

Cálculo del impacto económico para Chile del uso de losartán en diabéticos tipo 2 con nefropatía diabética, basado en resultados del estudio RENAAL / Economic impact of Losartan use in type 2 diabetic patients with nephropathy

Background: The study RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) demonstrated that Losartan was more effective lo reduce the progression of kidney disease in diabetic patients with proteinuria and a reduction in glomerular filtration rate. Aim: To perform a cost benefit analysis of Losartan use from provider and payer points of view. Material and methods: Published data of the RENAAL study was analyzed. The costs of the use or not use of Losartan in patients with diabetic nephropathy were compared in terms of total costs of the disease including medications, hospital admissions for myocardial infarction, cerebrovascular accidents and congestive cardiac failure and the costs of chronic hemodialysis. Results: The reduction in antihypertensive medication use, hospital admissions, and the delay in dialysis requirement from a mean of 65 to 79 months induced by Losartan use, results in net savings of $7,576,135 per patient, at 3.5 years of intervention. The figure does not change using different sensitivity scenarios. Conclusions: The eventual use of Losartan in type 2 diabetic patients results in important savings.

Persistent hypertension and progressive renal injury induced by salt overload after short term nitric oxide inhibition

INTRODUCTION: Administration of the NO inhibitor Nwð-nitro-L-arginine methyl ester (NAME) and a high-salt diet (HS) promotes severe albuminuria and renal injury, which regresses upon discontinuation of treatments. OBJECTIVE: We investigated whether these changes reappear after reinstitution of HS, and whether they are prevented by treatment with the antilymphocyte agent mycophenolate mofetil (MMF) or the AT-1 receptor blocker losartan (L). Adult male Munich-Wistar rats received NAME and HS. A control Group (C) received only HS. After 20 days, rats receiving HS and NAME exhibited severe hypertension and albuminuria. After a 30-day recovery period, hypertension was attenuated and albuminuria had virtually disappeared. MATERIAL AND METHODS: Rats were then distributed among the following groups: HS, receiving HS; NS, receiving a normal salt (NS) diet; HS-MMF, receiving HS and MMF; HS-LOS, receiving HS and L; HS-HDZ, receiving HS and hydralazine (HDZ). Sixty days later, NS rats showed only slight albuminuria and renal damage or inflammation. In contrast, HS rats developed severe hypertension, marked glomerulosclerosis with interstitial expansion and renal infiltration by macrophages and angiotensin II-positive cells. The group treated with losartan had lowered blood pressure and a lack of albuminuria or renal injury. MMF provided similar protection without altering blood pressure, suggesting a nonhemodynamic effect, a hypothesis reinforced by the finding that HDZ lowered blood pressure without preventing renal injury. RESULTS: These results indicate that treatment with HS and NAME predisposes to the development of hypertension and renal injury upon salt overload, characterizing a new model of chronic nephropathy. CONCLUSION: The response to MMF or L, but not HDZ, suggests a key role for inflammatory rather than hemodynamic factors.

INTRODUÇÃO: A administração de Nômega-nitro-L-arginina metiléster (NAME), um inibidor da produção de NO, com dieta rica em sal (HS) promove albuminúria e dano renal graves, reversíveis ao interromperem-se os tratamentos. OBJETIVO: Investigamos se tais alterações recrudescem ao reinstituir-se a HS e se são prevenidas pelo micofenolato mofetil (MMF), um agente antilinfócito, ou losartan, um bloqueador do receptor AT-1. MATERIAL E MÉTODOS: Ratos Münich-Wistar machos adultos receberam NAME e HS. Um grupo controle (C) recebeu apenas HS. Após 20 dias, os ratos que receberam HS e NAME exibiam hipertensão e albuminúria graves. Após recuperação de 30 dias, a hipertensão atenuou-se e a albuminúria praticamente desapareceu. Formaram-se então os grupos: HS, recebendo HS; NS, recebendo dieta normal em sal (NS); HS-MMF, recebendo HS e MMF; HS-LOS, recebendo HS e losartan; HS-HDZ, recebendo HS e hidralazina. Após sessenta dias os ratos NS tinham albuminúria e dano/inflamação renal apenas discretos. Já os ratos HS desenvolveram hipertensão e glomerulosclerose acentuadas, expansão intersticial e infiltração renal por macrófagos e células positivas para angiotensina II. Losartan baixou a pressão arterial e preveniu albuminúria e lesão renal. MMF proporcionou proteção semelhante sem alteração pressórica, sugerindo a ação de mecanismos não hemodinâmicos, hipótese reforçada pelo achado de que a HDZ baixou a pressão arterial sem prevenir a nefropatia. RESULTADOS: Esses resultados indicam que o tratamento com HS e NAME predispõe ao desenvolvimento de hipertensão e lesão renal induzidos por excesso de sal, caracterizando um novo modelo de nefropatia crônica. CONCLUSÃO: A resposta ao MMF ou losartan, mas não à hidralazina, sugere o predomínio de fatores inflamatórios.

The impact of losartan on the lifetime incidence of ESRD and costs in Mexico / El impacto del losartan en la incidencia de por vida de la enfermedad renal de la etapa terminal y sus costos en México

Background. The RENAAL (Reduction of Endpoints in Type 2 Diabetes with the Angiotensin II Antagonist Losartan) study demonstrated that treatment with losartan reduced the risk of ESRD by 29% among hypertensive patients with type 2 diabetes and diabetic nephropathy. The objective of this study was to project the effect of losartan compared to placebo on the lifetime incidence of ESRD and associated costs from a third-party payer perspective in Mexico. Methods. A competing risks method was used to estimate lifetime incidence of ESRD, while accounting for the risk of death without ESRD. The cost associated with ESRD was estimated by combining the cumulative incidence of ESRD with the lifetime cost associated with ESRD. Total cost was estimated as the sum of the cost associated with ESRD from the three main public institutions in Mexico, the lifetime cost of losartan therapy, and other costs (non-ESRD/non-losartan) expected for patients with type 2 diabetes. Survival was estimated by weighting the life expectancies with and without ESRD by the cumulative risk of ESRD. Results. The projected lifetime incidence of ESRD for losartan patients was lower (66%) compared with placebo patients (83%). This reduction in ESRD resulted in a decrease in ESRD-related cost of M$49,737 per patient and a discounted gain of 0.697 life years per patient. After accounting for the cost of losartan and the additional cost associated with greater survival, we projected that treatment with losartan would result in a net savings of M$24,073 per patient. Conclusion. Treatment with losartan in patients with type 2 diabetes and nephropathy not only reduced the within-trial incidence of ESRD but is projected to result in lifetime reductions in ESRD, increased survival, and overall cost savings to public institutions in Mexico.

Antecedentes. El estudio RENAAL (Reducción de los grados o puntos terminales en la diabetes tipo 2 con losartan, el antagonista de la anglotenslna II) demostró que el tratamiento con losartan redujo el riesgo de la ESRD (enfermedad renal de la etapa terminal) en 29% entre pacientes hipertensos con diabetes tipo 2 y neuropatía diabética. El propósito estudiado fue hacer una proyección del efecto del losartan comparándolo con el placebo en la incidencia de por vida de la ESRD y con los costos asociados de un tercer pagador en perspectiva en México. Métodos. Se utilizó un método de riesgos muy competitivo para calcular la incidencia de por vida de la ESRD, al mismo tiempo que se calculaba el riesgo de muerte sin la ESRD. El costo asociado con la ESRD se calculó confirmando la incidencia acumulativa de la ESRD en relación con el costo de por vida de la terapia con losar-tan y otros costos (sin ESRD o sin losartan) con los que se contaba para pacientes con diabetes tipo 2. La supervivencia se calculó esperando las expectativas de vida con y sin ESRD por el riesgo acumulativo de ESRD. Resultados. La proyectada incidencia de por vida de la ESRD en cuanto a los pacientes con losartan fue más baja (66%) comparada con los pacientes que tomaron placebo (83%). Esta reducción de la ESRD tuvo por resultado una disminución en el costo relacionado con la ESRD de $49,737 por paciente y una ganancia descartada de 0.697 años de vida por paciente. Luego de contabilizar el costo del losartan y el costo añadido asociado con una mayor supervivencia, llegamos a la conclusión de que el tratamiento con losartan daría por resultado un ahorro neto de $24,073 por paciente. Conclusión. El tratamiento mediante losartan en pacientes aquejados de diabetes tipo 2 y neuropatía no sólo redujo la incidencia intraexperimental de la ESRD, sino que además nos ha servido para proyectar que resulte en reducciones de por vida en la ESRD, en una supervivencia incrementada y en un ahorro total de costos en cuanto a las instituciones públicas en nuestro país.

Acute AT1 receptor blockade does not improve the depressed baroreflex in rats with chronic renal hypertension

To assess the role of angiotensin II in the sensitivity of the baroreflex control of heart rate (HR) in normotensive rats (N = 6) and chronically hypertensive rats (1K1C, 2 months, N = 7), reflex changes of HR were evaluated before and after (15 min) the administration of a selective angiotensin II receptor antagonist (losartan, 10 mg/kg, iv). Baseline values of mean arterial pressure (MAP) were higher in hypertensive rats (195 ± 6 mmHg) than in normotensive rats (110 ± 2 mmHg). Losartan administration promoted a decrease in MAP only in hypertensive rats (16 percent), with no changes in HR. During the control period, the sensitivity of the bradycardic and tachycardic responses to acute MAP changes were depressed in hypertensive rats (~70 percent and ~65 percent, respectively) and remained unchanged after losartan administration. Plasma renin activity was similar in the two groups. The present study demonstrates that acute blockade of AT1 receptors with losartan lowers the MAP in chronic renal hypertensive rats without reversal of baroreflex hyposensitivity, suggesting that the impairment of baroreflex control of HR is not dependent on an increased angiotensin II level