RESUMEN
The Aspirin in Reducing Events in the Elderly (ASPREE) Trial recruited 19,114 participants across Australia and the United States during 2010-2014. Participants were randomized to receive either 100 mg of aspirin daily or matching placebo, with disability-free survival as the primary outcome. During a median 4.7 years of follow-up, 37% of participants in the aspirin group permanently ceased taking their study medication and 10% commenced open-label aspirin use. In the placebo group, 35% and 11% ceased using study medication and commenced open-label aspirin use, respectively. In order to estimate compliance-adjusted effects of aspirin, we applied rank-preserving structural failure time models. The results for disability-free survival and most secondary endpoints were similar in intention-to-treat and compliance-adjusted analyses. For major hemorrhage, cancer mortality, and all-cause mortality, compliance-adjusted effects of aspirin indicated greater risks than were seen in intention-to-treat analyses. These findings were robust in a range of sensitivity analyses. In accordance with the original trial analyses, compliance-adjusted results showed an absence of benefit with aspirin for primary prevention in older people, along with an elevated risk of clinically significant bleeding.
Asunto(s)
Aspirina , Hemorragia , Humanos , Estados Unidos/epidemiología , Anciano , Anciano de 80 o más Años , Aspirina/uso terapéutico , Hemorragia/inducido químicamente , Australia/epidemiología , Método Doble CiegoRESUMEN
BACKGROUND: Not only is depression associated with increased inflammation but inflammation is a risk factor for the genesis of depression. Many of the environmental risk factors for depression are transduced through inflammatory signaling. Anti-inflammatory agents show promise for the management of depression in preclinical, epidemiological, and early clinical studies. This opens the door to the potential for anti-inflammatory agents to treat and prevent depression. There are no evidence-based pharmacotherapies for depression prevention. METHOD: ASPREE-D, aspirin in the prevention of depression in the elderly, is a sub study of ASPREE, which explores the potential of aspirin to prevent a range of inflammation related disorders in the elderly. With a sample size of 19,114, and a duration of 5 years, this placebo controlled study will be one of the largest randomized controlled trials in psychiatry and will provide definitive evidence on the ability of aspirin to prevent depression. RESULTS: This paper presents the rationale for the study and presents a summary of the study design. CONCLUSIONS: ASPREE-D may not only define novel therapy but will provide mechanistic proof of concept of the role of inflammation in depression.