Discussion
bleeding, ischemic strokes, intracerebral hemorrhagic, intracerebral hemorrhage, intracranial hemorrhage, stroke, intracranial hemorrhagic, strokes, primary stroke, ischemic stroke, hemorrhage, subarachnoid hemorrhage, hypertensive arteriopathy, Head injury, trauma
BLEEDING, ISCHEMIC STROKES, INTRACEREBRAL HEMORRHAGE, INTRACRANIAL HEMORRHAGE, STROKE, INTRACRANIAL BLEEDING, EXTRADURAL HEMORRHAGE, ISCHEMIC STROKE, HEMORRHAGE, SECONDARY, SUBARACHNOID HEMORRHAGE, SUBDURAL HEMATOMAS, EVENTS, PATHOLOGY, STROKES
To our knowledge, the ASPREE randomized clinical trial is the first large-scale trial to study the risks and benefits of aspirin in an exclusively older primary prevention population, in which an increased tendency to bleeding may alter the balance of risks and benefits of aspirin. This is particularly relevant to intracerebral events because intracranial hemorrhage is typically less treatable than ischemic events and more frequently fatal or disabling.The principal finding of this secondary analysis of a randomized clinical trial was an increase in intracerebral hemorrhagic events, which in absolute terms outweighed a smaller and nonsignificant reduction in ischemic strokes. Despite the older age of the cohort, incidences of both types of events were low, with an overall rate of 5.8 per 1000 person-years of follow-up. The incidence of ischemic stroke was 0.5 incidents per 1000 person-years of follow-up lower, which was not statistically significant, while that of intracranial hemorrhage was 0.7 incidents higher, which was statistically significant.These data extend previously reported findings on stroke outcomes in ASPREE by focusing on first stroke and bleeding events and by directly comparing the potential benefit of aspirin on ischemic stroke prevention with risks of intracranial bleeding.The lack of an effect of aspirin in reducing ischemic stroke was notable given the higher age-related risk in this population and reported efficacy of aspirin in secondary stroke prevention.Among individuals randomized to aspirin, there were additional cases of intracerebral, subdural, and extradural hemorrhage, some occurring after trauma and others occurring spontaneously. No subgroup was identified in which the risk of hemorrhage was substantially different from the mean. Head injury, typically resulting from falls, is common in older individuals, and additional cases of bleeding after such occurrences are an important component of the risk-benefit equation of any antiplatelet agent in older adults. Most additional cases of intracerebral hemorrhage (8/12 events) occurred in the basal ganglia, where hypertensive arteriopathy is considered to be the dominant pathology.Poor clinical outcomes after intracranial hemorrhagic events were reflected in higher mortality rates. Although intracerebral hemorrhage constituted 21.6% of strokes, one-third of these (29/86 strokes) were fatal compared with 7.7% of ischemic strokes (24/312 strokes). The fatality rate after subarachnoid hemorrhage and subdural hematomas was similar among individuals randomized to aspirin or placebo treatment (Overall, results are in keeping with meta-analyses reported by the Antithrombotic Trialists’ Collaboration in 2009,The lack of benefit and potential risks from aspirin in primary stroke prevention provide further evidence in support of the recently published draft recommendation of the USPSTF against the routine prescribing of low-dose aspirin as a primary prevention measure, especially in older persons.