Prevention by low dose aspirin of cardiovascular disease in the elderly - PACE
Aspirin vs. placebo for primary prevention in elderly patients
To examine the efficacy and safety of low-dose aspirin for primary prevention of atherosclerotic cardiovascular and cerebrovascular disease in the elderly.
- Placebo Controlled
Patients Screened: Not given
Patients Enrolled: 400 (pilot) 15,000 (planned for main trial)
Mean Follow Up: 12 months
- Age ≥70 years
- Significant vascular disease
- Septic ulceration
- Hemorrhagic symptoms
- Currently taking non-steroidal anti-inflammatory drugs
Compliance with medication (assessed by pill count and platelet function tests), self-reported drop-out and drop-in rates, and incidence of cardiovascular events reported by participants and their general practitioners during a 12-month period.
Low-dose enteric-coated aspirin (100 mg daily), or placebo.
Subjects were randomized so that 200 subjects received aspirin and 200 subjects received placebo.
Compliance to medication was excellent (87%), and premature withdrawal (other than for a study end point) was limited to 14.5%.
Two fatal cardiovascular events, three non-fatal coronary events, and eight non-fatal cerebrovascular events were observed during the 12-month period. These incidence figures were approximately 15%, 15%, and 40%, respectively, of those in the general population of the same age and sex, based on morbidity data available from the Australian Bureau of Statistics.
Secondary endpoints, such as transient ischaemic attack and unstable angina, necessitated patient withdrawal from randomized therapy and possibly contributed to the small number of primary 'hard' end points observed.
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).
The projected sample size of the main study to detect with 80% power a 20% treatment effect on overall cardiovascular mortality was 15,000 subjects over a 4-year period.
These results suggest that any future primary prevention study of cardiovascular disease in the elderly examining the effect of low-dose aspirin on overall cardiovascular mortality will likely need to use much larger numbers of patients or use a combined end point of fatal and non-fatal ischemic events.
1. J Am Geriatr Soc 1991;39:484-91. Study design
2. Clin Pharmacol Ther 1993;54:84-9. Interim pilot results
3. J Am Geriatr Soc 1994;42:643-7. Pilot results
Keywords: Hemoglobins, Platelet Aggregation Inhibitors, Cerebrovascular Disorders, Diuretics, Heart Failure, Coronary Disease, Primary Prevention, ESC Congress
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