Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment)

ABSTRACT: The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy.

Efeitos da pentoxifilina na anemia resistente à eritropoetina em pacientes sob hemodiálise / Pentoxifylline effects on the resistant anemia to erythropoietin in hemodialysis patients

A anemia na insuficiência renal crônica deve-se à redução da produção de eritropoetina, devido à diminuição da massa renal funcionante. A eritropoetina tem sido preconizada para o tratamento da anemia, no entanto, cerca de 5 por cento dos pacientes são resistentes à mesma. A resistência à eritropoetina é definida como a necessidade do uso de uma dose maior que 12.000U/kg por semana, sem atingir o hematócrito alvo de 33 por cento a 36 por cento. As citocinas pró-inflamatórias têm uma associação importante com a anemia resistente ao tratamento com eritropoetina (EPO). A pentoxifilina tem sido usada para inibir a produção dessas citocinas pró-inflamatórias. Este estudo foi realizado com os pacientes sob hemodiálise no Instituto de Nefrologia Ribamar Vaz, do Hospital da Santa Casa de Misericórdia de Maceió-Al. Os pacientes com diagnóstico de resistência à eritropoetina receberam pentoxifilina na dose de 400 mg VO, após hemodiálise por seis meses. Avaliamos o hematócrito e a proteína C reativa (PCR) em dois momentos: ao final de três meses com 12 pacientes e, ao final de seis meses, com sete pacientes. A média de PCR dos 12 pacientes, no primeiro mês, foi de 5,65 mg/l. No terceiro mês, de 2,58 mg/l. Porém, no sexto mês, considerando apenas os sete que terminaram o projeto, foi de 4,55 mg/l. Não foi observada diferença significativa. A média final dos hematócritos(Htc) observada nos pacientes foi de 28,74 por cento. A média dos Htc na avaliação de seis meses que precederam o início do projeto, foi de 26,22 por cento. Não foi observada diferença estatisticamente significante, quer nos 12 pacientes acompanhados por três meses ou nos sete que conseguiram concluir o estudo. Não observamos correlação entre os níveis de PCR e os de hematócrito. No entanto, em nossa amostragem, a média de PCR basal não estava elevada e este pode ter sido um fator importante nos resultados díspares em relação aos dados da literatura. Sendo assim, concluímos que, em...

Anemia in end stage renal disease occurs due to the reduction in the production of erythropoietin caused by the decrease in functional renal mass. Erythropoietin has been indicated in the treatment of anemia however, about 5 percent of patients are resistant to this treatment. In erythropoietin resistance, it is necessary to increase the dosage to more than 12000 U/Kg/weekly, but even so the hematocrit target, which should remain between 33 and 36 percent, is not reached. Pro-inflammatory cytokines are significantly associated to resistance to erythropoietin treatment and so pentoxifylline is used to inhibit the production of these pro-inflammatory cytokines. This study was carried out with hemodialysis patients at the Ribamar Vaz Institute of Nephrology - in the Santa Casa de Misericórdia Hospital of Maceió. Patients with diagnoses of resistance to erythropoietin received 400mg VO pentoxifylline after hemodialysis over a period of six months. The hematocrit and C-reactive protein (CRP) concentrations were analyzed three times: in the first month, at the end of three months (12 patients) and at the end of six months (7 patients). The mean CRP of the 12 patients in the first month was 5.65 and in the third month it was 2.58. However, in the sixth month, with the 7 patients remaining in the protocol, it was 4.55. No significant differences were observed. The final average hematocrit concentration of the patients was 28.74 percent. The average hematocrit concentration, in the six-month evaluation that preceded the project, was 26.22 percent. Statistically-relevant differences were not observed in the 12 patients followed up for 3 months or in the 7 that concluded the study. No correlations between the levels of CRP and hematocrit concentration were observed. However, in our sampling, the mean basal CRP was not high and this might have been an important factor to explain the difference between our results and other published reports. Thus,...