Risk of low-dose aspirin outweighs benefit in general population

Low-dose daily aspirin may be effective as a preventive therapy for heart patients with symptomatic atherosclerotic disease, but in the general population the drug’s risk of intracranial bleeding outweighs any CV benefits it may have, according to a study published May 13 in JAMA Neurology.

The benefits of low-dose aspirin—100 mg per day or less—in patients diagnosed with heart disease are well-established, first author Wen-Yi Huang, MD, PhD, and colleagues at Chang Gung University College of Medicine and Chang Gung Memorial Hospital in Taiwan, wrote in the journal. But the therapy’s nature as a blood thinner means it carries its fair share of risks, too, including major bleeding and intracranial hemorrhage.

“Because of the devastating nature of intracranial hemorrhage outcomes, inconsistent published data on the risk of intracranial hemorrhage for individuals taking aspirin for primary prevention, the paucity of information on specific subtypes of intracranial hemorrhage and recently published clinical trials, we conducted a systematic review and meta-analysis of randomized clinical trials to clarify the qualitative and quantitative links of aspirin for primary prevention,” Huang et al. wrote.

The team combed PubMed and Embase databases, as well as the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov, for randomized trials comparing low-dose aspirin to a control between 1966 and 2018. They identified 13 clinical trials that enrolled a cumulative 134,446 patients, analyzing those studies’ findings for main outcomes of intracranial hemorrhage, intracerebral hemorrhage, subdural or extradural hemorrhage and subarachnoid hemorrhage.

After pooling the results of a random-effects model, Huang and co-authors said low-dose aspirin, compared with a control, was linked to a 1.37-fold increased risk of any intracranial bleeding in eight of the trials they studied. They said the greatest relative risk was for subdural or extradural hemorrhage, which was associated with a 1.53-fold increased risk in four trials.

“The absolute magnitude of these adverse effects is modest, but clinically relevant,” the authors wrote. “Among every 1,000 people treated with low-dose aspirin instead of control, two more had intracranial hemorrhagic events. Intracranial hemorrhage events are generally associated with higher mortality and greater disability than ischemic events associated with atherosclerotic cardiovascular disease, such as ischemic stroke.”

The team said the risk of intracranial bleeding was highest in Asian patients and those with a body mass index of less than 25. They said the former finding is consistent with other studies, which have shown the ratio of hemorrhagic stroke to ischemic stroke is higher in Asian than in non-Asian populations. Asian race and lower BMIs are also known to covary.

“The current study provides an updated perspective on the association of preventive low-dose aspirin and subdural and extradural hemorrhage,” Huang et al. said. “Because the benefits of low-dose aspirin for primary prevention of cardiovascular events are not well-established, and the outcomes of intracranial hemorrhage are often catastrophic, these findings suggest caution regarding using low-dose aspirin in individuals without symptomatic cardiovascular disease.”