Greta H. Camel

Recruitment of elderly volunteers for a multicenter clinical trial: The SHEP pilot study☆

Few large trials have involved the elderly, and little is known about the feasibility of recruiting such participants for study and the validity of inferences drawn from them. This article reviews the recruitment experience of the Systolic Hypertension in the Elderly Program (SHEP) pilot study. That program involved five clinical centers, and contacted approximately 75,000 persons in order to enroll a cohort of 551 individuals over 60 years old isolated systolic hypertension. The enrolled cohort was somewhat older and more highly educated than those screened. Except for deliberate oversampling of blacks and those over 70 years old, the enrolled population resembled the U.S. population, although individuals in the SHEP group were initially healthier, and more likely to have had some college education than those in the general population. There was substantial variation among sites in number of staff hours spent per participant recruited. The SHEP experience indicates that older persons are willing to volunteer for clinical trials research and that problems of inference are probably not any greater for that age group than for any other.

Studies on the Control of Hypertension: VIII. Mortality, Morbidity, and Remissions During Twelve Years of Intensive Therapy

EFFECTIVE pharmacological control of severe arterial hypertension has been available for more than a decade. A combination of an orally administered ganglioplegic agent and hydralazine was first found to induce sustained reduction of blood pressure to normal or nearly normal levels in the summer of 1951,1 and a practical therapeutic regimen was quickly developed.2 A large series of patients, selected only for severity of the hypertensive process, was treated with this regimen in order to evaluate its long-term effects on mortality and morbidity. Interim reports on various aspects of the study have been published.3-6 The present report concerns 316 patients suffering from moderately severe and severe hypertension who began to ingest ganglioplegic agents and hydralazine more than 7 years ago; almost half of them began more than 12 years ago. Therapy was intensive, as doses of drugs large enough to produce the desired antihypertensive effect were employed in every case. This report cites the mortality associated with differing severities of hypertensive disease. It examines the significance of advanced hypertensive retinopathy by comparing patients exhibiting this finding with those having other hypertensive complications. The time and cause of death are considered as

Survival in hydralazine-treated hypertensive patients with and without late toxicity.

Abstract Part I, Average diastolic pressure was examined in two groups of white patients during 10 yr of treatment with hydralazine for significant hypertension. The first group consisted of 42 patients who developed late toxic reactions to hydralazine. The control group consisted of 42 similarly treated non-toxic patients matched for age, sex, and pre-treatment severity of hypertension. The average diastolic pressure was lower for the toxic patients throughout the period of hydralazine exposure. The effect was evident within a month of starting treatment; it was maximal during toxicity, and it apparently persisted long after the toxic patients discontinued ingesting hydralazine. More importantly, the once-toxic patients survived almost a third longer than their ‘matches’, and the number of survivors at both 10 and 15 yr after starting therapy was significantly greater for toxic than non-toxic patients. Finally, there was a marked difference in survival within the group of once-toxic patients, with those who continued markedly reduced doses of hydralazine for 18 months or more after toxic symptoms appeared, surviving more than twice as long as those who discontinued hydralazine within two months of their first toxic symptom. Part II, For 168 non-toxic white patients, whose hypertension was treated with hydralazine plus ganglioplegic agent, long-term survival was significantly related to therapeutic response as follows: (1) Patients with ‘controlled’ hypertension survived 60% longer than those with ‘partly controlled’ hypertension. (2) Patients who required 2 3 or less of their initial dose of hydralazine after a year of treatment survived 85% longer than those who required 3 2 or more of their initial dose. (3) Patients without leucopenia, anemia, or dysglobulinemia survived 50% longer than those with such changes. (4) Patients whose cholesterol levels fell more than 50 mg/100 ml of plasma below their pre-treatment values survived 70% longer than those whose levels increased.

Effect of Diuretic-Based Antihypertensive Treatment on Cardiovascular Disease Risk in Older Diabetic Patients with Isolated Systolic Hypertension

OBJECTIVE To assess the effect of low-dose, diuretic-based antihypertensive treatment on major cardiovascular disease (CVD) event rates in older, non-insulin-treated diabetic patients with isolated systolic hypertension (ISH), compared with nondiabetic patients. DESIGN Double-blind, randomized, placebo-controlled trial: the Systolic Hypertension in the Elderly Program (SHEP). SETTING Multiple clinical and support centers in the United States. PARTICIPANTS A total of 4736 men and women aged 60 years and older at baseline with ISH (systolic blood pressure [BP], > or = 160 mm Hg; diastolic BP, <90 mm Hg) at baseline, 583 non-insulin-dependent diabetic patients and 4149 nondiabetic patients (4 additional patients not so classifiable were randomized but not included in these analyses). Diabetes mellitus defined as physician diagnosis, taking oral hypoglycemic drugs, fasting glucose level of 7.8 mmol/L or more (> or = 140 mg/dL), or any combination of these characteristics. INTERVENTION The active treatment group received a low dose of chlorthalidone (12.5-25.0 mg/d) with a step-up to atenolol (25.0-50.0 mg/d) or reserpine (0.05-0.10 mg/d) if needed. The placebo group received placebo and any active antihypertensive drugs prescribed by patients private physician for persistently high BP. MAIN OUTCOME MEASURES The 5-year rates of major CVD events, nonfatal plus fatal stroke, nonfatal myocardial infarction (MI) and fatal coronary heart disease (CHD), major CHD events, and all-cause mortality. RESULTS The SHEP antihypertensive drug regimen lowered BP of both diabetic and nondiabetic patients, with few adverse effects. For both diabetic and nondiabetic patients, all outcome rates were lower for participants randomized to the active treatment group than for those randomized to the placebo group. Thus, 5-year major CVD rate was lower by 34% for active treatment compared with placebo, both for diabetic patients (95% confidence interval [CI], 6%-54%) and nondiabetic patients (95% CI, 21%-45%). Absolute risk reduction with active treatment compared with placebo was twice as great for diabetic vs nondiabetic patients (101/1000 vs 51/1000 randomized participants at the 5-year follow-up), reflecting the higher risk of diabetic patients. CONCLUSION Low-dose diuretic-based (chlorthalidone) treatment is effective in preventing major CVD events, cerebral and cardiac, in both non-insulin-treated diabetic and nondiabetic older patients with ISH.