Rationale for a Primary Prevention Study Using Low‐Dose Aspirin To Prevent Coronary and Cerebrovascular Disease in the Elderly

Abstract

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. Sample size calculations have indicated that 15,000 subjects would be required over a 4-year follow-up period in order to demonstrate a 20% reduction in overall cardiovascular mortality at the 0.01 level with a power of 0.8. Such a large-scale community-based clinical trial has never been conducted in Australia in this age group. Therefore the PACE (prevention by low-dose aspirin of cardiovascular disease in the elderly) pilot study has been developed to test recruitment strategies and methods and ascertaining disease end-points.

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

“…The methods used for the PACE pilot trial have been described in detail previously 6,7 and are only summarized here briefly.…”

“…We sought to avoid this problem by designing a primary prevention trial of low‐dose aspirin therapy in an elderly population, where the absolute risk of cardiovascular disease is substantially higher than in middle‐aged subjects 6 . As a result of the consequent increase in expected event rates, fewer subjects are likely to be required to demonstrate the effectiveness of the intervention.…”

“…As a result of the consequent increase in expected event rates, fewer subjects are likely to be required to demonstrate the effectiveness of the intervention. The detailed rationale and sample size calculations for the PACE (Prevention with low‐dose Aspirin of Cardiovascular disease in the Elderly) study have been described previously 6 . We initially assumed that the participants in the PACE trial would develop cardiovascular events at two‐thirds the rate reported in the general population of the same age and sex.…”

Acetylsalicylic acid for primary prevention of cardiovascular diseases in older patients with diabetes: do the benefits overcome the risks?

“…To our knowledge, only two randomized trials have specifically targeted older people. First, the PACE trial (Prevention with low-dose Aspirin of Cardiovascular disease in the Elderly) was a randomized, double-blind, placebo-controlled trial involving people aged 70 years and older [Silagy et al 1991[Silagy et al , 1994. ASA dose was 100 mg daily.…”

Study design of ASPirin in Reducing Events in the Elderly (ASPREE): A randomized, controlled trial

“…The study was originally planned as a primary prevention cardiovascular disease (CVD) outcome study in the early 1990s to address the lack of aged participants in contemporary trials [6, 7, 12, 13]. The current iteration commenced in 2002 with the rationale still evident but expansion of the endpoints to include other prevalent diseases in the aged [8-11, 14, 15].…”