Christopher A. Silagy

Adverse effects of low-dose aspirin in a healthy elderly population.

The adverse effects of low‐dose aspirin (100 mg daily) in the elderly were studied over a 12‐month period in a double‐blind, randomized, placebo‐controlled trial of 400 subjects who were 70 years of age or older and had no preexisting major vascular diseases at the time of entry. Subjects were randomized so that 200 subjects received low‐dose enteric‐coated aspirin (100 mg daily) and 200 subjects received placebo. Compliance with medication, assessed by pill count, was 86%. Gastrointestinal symptoms were reported by 18% (n = 36) of participants receiving aspirin and 13% (n = 26) of those receiving placebo. Clinically evident gastrointestinal bleeding occurred in 3% (n = 6) of subjects receiving aspirin and none receiving placebo. Aspirin‐treated subjects had a significant decrease in mean hemoglobin levels of 0.33 gm/dl during the 12‐month study period, which was significantly greater than the decrease in the placebo‐treated group (0.11 gm/dl; p < 0.05). These rates of unwanted symptoms are comparable with previous studies that used higher doses of aspirin. Until the risk‐benefit trade‐off from the use of low‐dose aspirin in the elderly is established with an appropriate clinical trial, caution should be exercised when this compound is used for primary prevention of cardiovascular disease in this age group.

Comparison of recruitment strategies for a large-scale clinical trial in the elderly

Formal evaluation of recruitment strategies for clinical trials conducted in the community setting, rather than in hospitals, is limited despite recruitment rates and costs having significant implications for the planning of large trials. As part of the development of a large-scale primary prevention trial of low-dose aspirin in 15,000 elderly persons (aged 70 years and above) to be undertaken in a community setting, a pilot study involving 400 participants was carried out to evaluate different recruitment strategies. Three techniques were compared: recruiting from the electoral roll (by individual invitation using direct mail), local community approach (through retirement villages, local media, elderly community groups), and using general/family practice (identifying persons over 70 within a practice and direct mail invitation to participate). Screening of potential participants was carried out by a trained trial nurse with limited involvement only of medical practitioners. The target recruitment figure was achieved in 4 months using the equivalent of 1.5 full-time nurses. General practice was the most effective method utilized, with a yield of one participant recruited per six approached at an estimated cost of A

Epidemiologic aspects of isolated systolic hypertension and implications for future research

48.36 per recruited participant. This compares with yield rates of 1 per 29 (for the local community approach) and 1 per 17 for the electoral roll, and costs per participant of A

The Pace Pilot Study: 12‐Month Results and Implications for Future Primary Prevention Trials in the Elderly

42.54 and A

COMPARISON OF REPEATED MEASUREMENT OF AMBULATORY AND CLINIC BLOOD PRESSURE READINGS IN ISOLATED SYSTOLIC HYPERTENSION

59.37 respectively. Other less tangible benefits of general practice include the greater cooperation of primary care practitioners in patient follow-up and end-point ascertainment.

Rationale for a primary prevention study using low-dose aspirin to prevent coronary and cerebrovascular disease in the elderly

Isolated systolic hypertension represents an important public health issue in the 1990s because of its prevalence in the elderly and its importance as a risk factor for cardiovascular morbidity and mortality. Methodologic differences may account for the wide variation between prevalence rates in studies reported. With the advent of newer methods of blood pressure (BP) assessment, such as noninvasive ambulatory BP monitoring, it may be possible to define more accurately the true population at risk. Recent data from the Systolic Hypertension in the Elderly Program has indicated a clear benefit of treatment with a reduction in total stroke of 36%, and a reduction of 25 and 32% in the combined end points of coronary heart disease and cardiovascular disease, respectively. Further studies are now required to elucidate what treatment regimens are most effective in preferentially reducing both systolic BP, without producing undesirable effects such as diastolic hypotension, and fatal and nonfatal events. One such trial is underway in Europe using a drug regimen different from that in the Systolic Hypertension in the Elderly Program. The cost implications associated with treating the population at risk are potentially large but these are now based on firm scientific evidence.

SAMPLE SIZE REQUIREMENTS FOR CLINICAL TRIALS OF ISOLATED SYSTOLIC HYPERTENSION

Objective: To document compliance with medication, dropout and drop‐in rates, and baseline cardiovascular event rates during the pilot phase of the PACE (Prevention with low‐dose Aspirin of Cardiovascular disease in the Elderly) study.

Crossover comparison of atenolol, enalapril, hydrochlorothiazide and isradipine for isolated systolic systemic hypertension

Repeated clinic blood pressure measurement was compared with non-invasive ambulatory blood pressure monitoring in 10 elderly subjects with persistent isolated systolic hypertension and 11 normotensive controls. Mean clinic blood pressures +/- Standard Deviation (SD), at visit 1 were 165/81 +/- 12/7 mmHg and 136/87 +/- 14/10 mmHg respectively. Subjects were assessed on three subsequent occasions at weekly intervals. None were receiving antihypertensive or vasoactive medication. Clinical systolic and diastolic blood pressures were consistently higher than the corresponding mean daytime ambulatory blood pressures in both clinical groups at each of the visits. The difference was greater between the systolic pressures than between the diastolic pressures and these differences in systolic pressures were greater in the isolated systolic hypertensives (26 +/- 5 mmHg) than in the normotensives (7 +/- 18 mmHg). Daytime ambulatory readings aggregated from all four visits were normally distributed for both blood pressure components in both clinical groups. In the isolated systolic hypertension group the clinic systolic and diastolic blood pressure measurements corresponded to the 93rd and 85th percentiles of the ambulatory pressures respectively whereas in the normotensives the equivalent percentiles were 69 and 78. These results suggest a pressor response may largely account for the elevated systolic blood pressure seen in elderly subjects with sustained isolated systolic hypertension based on clinic readings.

Isolated systolic hypertension : does it really exist on ambulatory blood pressure monitoring?

The benefits of prophylactic aspirin therapy to prevent cardiovascular and cerebrovascular disease in asymptomatic individuals remains unclear. The rationale for developing a multicentered, double‐blind, placebo‐controlled clinical trial to determine whether low‐dose aspirin (100 mg daily) prevents cardiovascular and cerebrovascular morbidity and mortality in persons aged 70 years and over with no evidence of pre‐existing cardiovascular or cerebrovascular disease is described.

Components of blood pressure variability in the elderly and effects on sample size calculations for clinical trials.

1. This study investigated components of blood pressure variability in elderly subjects with isolated systolic hypertension (ISH) using both ambulatory blood pressure monitoring (ABPM) and casual clinic blood pressure measurement. These were then used to determine sample size requirements for clinical trials of different designs.