Cost-effective strategies to maintain healthy active lifestyle in aging populations are required to address the global burden of age-related diseases. ASPREE will examine whether the potential primary prevention benefits of low dose aspirin outweigh the risks in older healthy individuals. Our primary hypothesis is that daily oral 100 mg enteric-coated aspirin will extend a composite primary endpoint termed ‘disability-free life’ including onset of dementia, total mortality, or persistent disability in at least one of the Katz Activities of Daily Living in 19,000 healthy participants aged 65 years and above (‘US minorities’) and 70 years and above (non ‘US minorities’). ASPREE is a double-blind, randomized, placebo-controlled trial of oral 100 mg enteric-coated acetyl salicylic acid (ASA) or matching placebo being conducted in Australian and US community settings on individuals free of dementia, disability and cardiovascular disease (CVD) events. Secondary endpoints are all-cause and cause specific mortality, fatal and non-fatal cardiovascular events, fatal and non-fatal cancer (excluding non-melanoma skin cancer), dementia, mild cognitive impairment, depression, physical disability, and clinically significant bleeding. To 20 September 2013 14383 participants have been recruited. Recruitment and study completion is anticipated in July 2014 and December 2018 respectively. In contrast to other aspirin trials that have largely focused on cardiovascular endpoints, ASPREE has a unique composite primary endpoint to better capture the overall risk and benefit of aspirin to extend healthy independent lifespan in older adults in the US and Australia.

Background: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; mid-term (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after PCI with DES. Methods: Twenty-four randomized controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The co-primary endpoints were myocardial infarction (MI) and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with random effects model. Results: In 79,073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of MI compared with 12-month DAPT (absolute risk difference [ARD], -3.8 incident cases per 1000 person-years; relative risk (RR), 0.68 [95% CI, 0.54-0.87]), mid-term DAPT (ARD, -4.6 incident cases per 1000 person-years; RR, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (ARD, -6.1 incident cases per 1000 personyears; RR, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (ARD, -3.7 incident cases per 1000 person-years; RR, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding compared with all other DAPT groups. Compared with 12-month DAPT, no significant differences in the risks of ischemic endpoints or major bleeding were observed with mid-term or short-term DAPT followed by aspirin monotherapy, except that shortterm DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome (ACS), extended-term compared with 12-month DAPT was associated with a reduced risk of MI without significant increase in the risk of major bleeding. Conclusions: The present network meta-analysis suggests that compared with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after PCI with DES, while extended-term DAPT reduces myocardial infarction at the expense of more bleeding events.

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