Low-dose aspirin should not be used for primary prevention in older people as it has no benefit and increases the risk of major bleeding events, an Australian RCT has shown.
Among the many outcomes assessed in the five-year Aspirin in Reducing Events in the Elderly (ASPREE) trial, Australian researchers showed that low-dose aspirin did not reduce the risk of stroke and was associated with an increase in intracranial bleeds compared to placebo.
The study compared the effects of 100mg daily aspirin and placebo in more than 19,000 healthy people over 70 in Australia and the US. Participants, who had no cardiovascular disease at baseline, showed no differences between aspirin and placebo in risk of a first heart attack or stroke and disability-free survival over a five year follow up period.
Rates of fatal and non-fatal ischaemic stroke were not significantly different for aspirin and placebo (3.5 vs 3.9/1000 person years, relative risk 0.89).
In a series of three papers published in NEJM, the trial investigators also showed that aspirin use was associated with a significant increase in in the number of cases of serious haemorrhagic events compared to the placebo group (8.6 vs 6.2 per 1000 person-years, hazard ratio, 1.38).
Gastrointestinal bleeding accounted for almost half the major haemorrhagic events. The risk of intracranial bleeding was also significantly higher with aspirin than with placebo (2.5 vs 1.7 events/1000 person years, hazard ratio, 1.50) and this finding was reflected across all subtypes of intracranial bleeding including haemorrhagic stroke and subarachnoid haemorrhage.
There was also a small increase in mortality rates for aspirin use, with a risk of death from any cause of 12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group (hazard ratio, 1.14).
Principal investigator Professor John McNeil (pictured), head of Monash University’s Department of Epidemiology and Preventive Medicine (pictured) said the trial findings show that many older people may be taking aspirin unnecessarily and there needs to be a rethink of global guidelines relating to aspirin use for prophylaxis.
“These findings will help inform prescribing doctors who have long been uncertain about whether to recommend aspirin to healthy patients who do not have a clear medical reason for doing so,” he said
Professor Garry Jennings, a cardiologist and Chief Medical Adviser at the Heart Foundation said the trial addressed an important health question about the balance of risks and benefits for aspirin in preventing clots but increasing bleeding risk.
“There is no more conclusive evidence of this issue than ASPREE which was well powered to clarify the risk vs benefits and conducted in an exemplary fashion,” he said.
“The results support the present Heart Foundation position that aspirin is not recommended for people without a history of heart disease. The present recommendations for people with heart problems to take aspirin on the advice of their doctor remain.
“ASPREE substantially clarifies the question of who should take aspirin and who should not and will thereby help save lives and prevent needless bleeding complications including stroke.
The trial investigators said the small increase in deaths observed in the aspirin group was primarily from cancer, and may be a chance finding since other large aspirin studies had suggested it may prevent cancer over the longer term.