W. McFate Smith

Systolic Hypertension in the Elderly Program (SHEP): Antihypertensive efficacy of chlorthalidone

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, blinded test of the efficacy of antihypertensive drug treatment. In a large feasibility trial, 551 men and women who had isolated systolic hypertension and were at least 60 years old received chlorthalidone (25 to 50 mg/day) or matching placebo as the step I drug. After 1 year, 83% of the chlorthalidone group and 80% of the placebo group were still taking SHEP medications. Of those still taking chlorthalidone, 88% had reached goal blood pressure (BP) without requiring a step II drug, and most had responded to the lower dose (25 mg/day). The BP response was similar in all age, sex and race subgroups, with an overall mean difference between randomized groups of 17 mm Hg for systolic BP (p less than 0.001) and 6 mm Hg for diastolic BP (p less than 0.001). The only common adverse effects were asymptomatic changes in the serum levels of potassium (0.5 mEq/liter lower in the chlorthalidone group, p less than 0.001), uric acid (0.9 mg/dl higher, p less than 0.001) and creatinine (0.08 mg/dl higher, p = 0.02). This study indicates that chlorthalidone is effective for lowering BP in elderly patients with systolic hypertension and sets the stage for a larger trial of the effects of such treatment on the incidence of cardiovascular disease.

Prevalence of postural hypotension at baseline in the systolic hypertension in the elderly program (SHEP) cohort

Objective: The objective of this study was to examine the prevalence and correlates of postural hypotension (defined as a drop in systolic blood pressure of ≥20 mm Hg) in a cohort of elderly persons with isolated systolic hypertension (ISH).

Systolic hypertension in the elderly program (SHEP): the first three months

T he Systolic Hypertension in the Elderly Program (SHEP) addresses the question: Should elderly patients with isolated systolic hypertension (ISH) receive antihypertensive drug treatment? The population we are concerned with is men and women age 60 years and older who consistently have a systolic blood pressure exceeding 160 mmHg and a diastolic blood pressure less than 90 mmHg. The goal of this report is to present the findings from the first three months of a study to demonstrate the feasibility of a full-scale randomized clinical trial. Specifically, we will address the issues of recruitment, compliance, treatment efficacy, and adverse effects.

Effects of Treatment for Isolated Systolic Hypertension on Cognitive Status and Depression in the Elderly

The Systolic Hypertension in the Elderly Program (SHEP) was designed as a feasibility study and in part dealt with the effects of the treatment of isolated systolic hypertension on cognitive status and depression. Subjects were 60 years of age or older with a systolic blood pressure of 160 mmHg or greater and diastolic of less than 90 mmHg; free of several specified illnesses or chronic conditions. These volunteers were randomly assigned to treatment (n = 443) and placebo (n = 108) groups. The behavioral assessments at baseline and 1 year later were the SHORT‐CARE instrument for depression, cognitive impairment, and disability and other tests of cognitive status (Digit Symbol Substitution and the Trail Making tests). Although the treatment regime was highly successful in controlling the hypertension, it did not have a significant impact on changes in cognitive function or level of depression; a behavioral benefit was not evident but the results are consistent with the view that an effective treatment regime for isolated systolic hypertension in the elderly can be behaviorally safe.

Use of Diuretics in Treatment of Hypertension in the Elderly

SummaryMen and women with isolated systolic hypertension who were at least 60 years of age were treated for 1 year with chlorthalidone (25–50mg daily) or matching placebo as the step I drug. Most patients reached goal blood pressure without requiring a step II drug. The blood pressure response was similar in all age, sex and race subgroups, with an overall difference between the randomised groups of 17mm Hg for systolic blood pressure (p<0.001) and 6mm Hg for diastolic blood pressure (p<0.001). The only common adverse effects were asymptomatic changes in the serum concentrations of potassium (0.5 mmol/L lower in the chlorthalidone group, p<0.001), uric acid (0.9 mg/dl higher, p<0.001), and creatinine (0.08 mg/dl higher, p=0.02. Compliance was good, and more than 80% of participants were still taking the study medications at the end of the year.RésuméLes hommes et les femmes porteurs d’une hypertension systolique isolée, âgés au moins de 60 ans, ont été traités, en première intention, pendant 1 an avec du chlorthalidone (25–50 mg par jour) ou par le traitement placebo apparié. La plupart des malades ont atteint la pression sanguine recherchée sans qu’il soit nécessaire de passer au degré II du traitement médicamenteux. La réponse de la pression sanguine a été similaire dans tous les sous-groupes âge, sexe et race, avec une différence extrême entre les groupes tirés au sort de 17 mmHg pour la pression systolique (p<0.001) et 6 mmHg pour la pression diastolique (p<0.001). Les effets indésirables les plus fréquents ont été des changements asymptomatiques dans les concentrations sériques de potassium (moins 0,5 mmol/l dans le groupe chlorthalidone, (p<0.001), d’acide urique (plus 0,9 mg/dl, p<0.001), et de créatinine (plus 0,08 mg/dl, p=0.02). L’adhésion au traitement a été bonne, et plus de 80% des participants continuaient de prendre leurs médicaments à la fin de l’année de traitement.ZusammenfassungMänner und Frauen mit einer isolierten systolischen Hypertonie, die mindestens 60 Jahre alt waren, wurden über ein Jahr mit Chlorthalidon (25–50 mg täglich) oder gleichartigem Placebo als Pharmaka der ersten Stufe behandelt. Die meisten Patienten erreichten den erwünschten Blutdruck, ohne daβ ein Medikament der zweiten Stufe erforderlich war. Die Blutdruck-Reaktion war in allen Alters-, Geschlechts-und Rassen-Untergruppen ähnlich mit einem Gesamtunterschied zwischen den randomisierten Gruppen von 17 mmHg für den systolischen Blutdruck (p<0,001) und 6 mmHg für den diastolischen Blutdruck (p<0,001). Die einzige gemeinsame Nebenwirkung bestand in einer asymptomatischen Veränderung des Kalium in den Serumkonzentrationen (0,5 mmol/L niedriger in der Chlorthalidon-Gruppe, p<0,001), Harnsäure (0,9 mg/dl höher, p<0,001) und Kreatinin (0,08 mg/dl höher, p=0,02 . Bei einer guten Compliance nahmen 80% der Teilnehmer die Medikationen der Untersuchung noch am Ende des Jahres.ResumenHombres y mujeres con hipertensión sistólica aislada, que tenían por lo menos 60 años de edad, se han tratado durante 1 año con clortalidona (25–50 mg diarios), o placebo de análogo aspecto, como fármaco de etapa I. La mayoría de los pacientes alcanzaron la presión deseada sin necesitar medicamento de etapa II. La respuesta tensional fue semejante en todos los grupos de edad, sexo y raza con una diferencia total entre los grupos aleatorizados de 17 mm Hg para la presion sistólica (p<0,001) y de 6 mm Hg para la diastólica (p<0,001). Los únicos efectos adversos de manifestación frecuente fueron modificaciones asintomáticas de las concentraciones séricas de potasio (0,5 mmol/l menos en el grupo clortalidona, p<0,001), de ácido úrico (0,9 mg/dl mas, p<0,001) y de cretinina (0,08 mg/dl más, p=0,02). La aceptación fue buena y más del 80% de participantes todavía estaban tomando las medicaciones en estudio al final del año.ResumoHomens e mulheres com hipertensão sistólica isolada e com idade mínima de 60 anos foram tratados por um ano com clortalidona (25 a 50 mg por dia) ou placebo equivalente como drogas de primeira escolha. A maioria dos pacientes atingiu o nível de pressão sanguínea objetivado sem recorrerem a outras drogas. A reação da pressão sanguínea foi semelhante em todos os subgrupos, fossem por idade, sexo ou raça, com uma diferença global entre os grupos selecionados de 17 mmHg para a pressão sistólica (p<0,001) e 6 mmHg para a pressão diastólica (p<0,001). Os únicos efeitos adversos comuns a todos foram mudanças assintomáticas nas concentrações de potássio no soro (0,5 mmol/L abaixo, no grupo com clortalidona, cortalidona, p<0,001), no ácido ùrico (0,9 mg/dl acima, p<0,001) e na creatinina (0,08 mg/dl acima, p=0,02). O indice de observância ao tratamento foi bom, sendo que mais de 80% dos participantes ainda estavam a tomar os medicamentos empregados durante a experiência ao final do ano.RiassuntoSoggetti di entrambi i sessi di almeno 60 anni con ipertensione sistolica isolata furono trattati per un anno con clortalidone (25–50 mg al giorno) o placebo, come farmaco di primo livello. La maggior parte dei pazienti normalizzarono la loro pressione arteriosa senza richiedere un farmaco di secondo livello. La risposta pressoria fu simile in tutti i sottogruppi di età, sesso e razza, con una differenza totale tra i gruppi randomizzati di 17 mm Hg per la pressione sistolica (p<0.001) e 6 mm Hg per la diastolica (p<0.001). I soli comuni effetti indesiderati furono modificazioni asintomatiche nette concentrazioni sieriche di potassio (di 0,5 mmol/1 inferiore nel gruppo trattato con clortalidone, p< 0.001), acido urico (di 0.9 mg/dl più alto, p<0.001) e creatinina (di 0.08 mg/dl maggiore, p<0.02). La compliance fu buona e più dell’80% dei partecipanti allo studio era ancora in trattamento alla fine dell’anno.

Isolated systolic hypertension in the elderly

SummaryIsolated systolic hypertension occurs principally in persons over 60 years of age, with its prevalence increasing from approximately 15% to twice that at age 75 years and over. The proportion of the U.S. population overage 60 years is also rising and is predicted to increase by nearly 40% by the end of the century. Excess cardiovascular risk, especially for stroke, is strongly associated with elevated systolic pressure. Isolated systolic hypertension is the most important unresolved issue in the management of high blood pressure. The importance of this issue is compounded by the fact that considerable uncertainty exists as to the risks and benefits of treatment. A pilot study to assess the feasibility of carrying out a full-scale trial of isolated systolic hypertension in the elderly is currently being undertaken. The selection and evaluation procedures to recruit at least 500 subjects and the randomized, double-blind stepped-care treatment programme to be followed in this long-term trial are descr...

The systolic hypertension in the elderly program

The Systolic Hypertension in the Elderly Program (SHEP) was a randomized multicenter double-blind placebo-controlled trial designed to test the efficacy of antihypertensive drug treatment in persons 60 years of age or older who had isolated systolic hypertension (ISH). ISH was defined as a systolic blood pressure (SBP) (160–219 mmHg) and a diastolic blood pressure (DBP) (< 90 mmHg). Prior to the completion of SHEP, ISH remained the most important unresolved therapeutic problem involving hypertension; no definitive data were available on the possible benefits of treating this condition. Previous randomized controlled trials on efficacy of antihypertensive drug treatment, including the few that included older people in their samples, have focused primarily on the problem of elevated DBP (90 mmHg or higher) and used diastolic hypertension as the sole or main entry criterion.

The Systolic Hypertension in the Elderly Program (SHEP): Rationale, Design, Recruitment, and Baseline Data

The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, double-blind, placebo-controlled trail to determine if antihypertensive treatment of isolated systolic hypertension (ISH) (systolic blood pressure [SBP] = 160 mmHg, diastolic blood pressure [DBP] < 90 mmHg) reduces the 5-year incidence of fatal and nonfatal stroke. Recruit ment was demanding; however, 4736 persons (target 4800) with ISH, age 60 years and over, were enrolled (1% of those initially contacted) between March 1, 1985 and January 15, 1988. Potential participants were those who met blood pressure criteria or those on antihypertensive medication and without documented diastolic hypertension who had their medication tapered and discontinued (consent obtained from participant and primary care physician) and then met blood pressure criteria.