— Randomized trial did show a significant reduction in non-fatal stroke
October 26, 2026 • 3 min read
DENVER -- Daily low-dose aspirin did not significantly reduce major vascular events in adults with chronic kidney disease (CKD), the randomized ATTACK trial showed.
Over a mean follow-up of 3.1 years, 2.4% of adults with CKD who took aspirin experienced a major vascular event -- a composite of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death -- compared with 3.3% of those who did not take aspirin, missing the trial's primary endpoint (HR 0.73, 95% CI 0.52-1.03, P=0.077).
When the primary endpoint was broken down, there was a significant reduction in non-fatal stroke with aspirin (HR 0.51, 95% CI 0.29-0.90, P=0.021). Differences for the remaining components did not reach significance, reported Hugh Gallagher, MBBS, PhD, of Epsom and St Helier University Hospitals NHS Trust in England.
"We're not in a place where we should be offering aspirin for primary prevention at this stage, but the question still needs answering," Gallagher said at the American Society of Nephrology Kidney Weekopens in a new tab or window annual meeting.
Low-dose aspirin is, however, recommended as secondary prevention for patients with CKD with a history of cardiovascular events.
"We know very well there's a strong association between markers of kidney disease and cardiovascular risk," Gallagher said. "As a result of that, there's a huge burden of cardiovascular disease in people with all stages of CKD. There's probably on the order of around 100,000 heart attacks and strokes per annum in the U.K. in people with stage 3 to 5 CKD ... but despite this, we still have relatively limited interventions to address this."
Aspirin was first commercially sold in 1899, he noted, "so 130 years later, we're still trying to work out what to do with it, and that's really because the effects of aspirin are very much a balance of benefit and harm."
While aspirin's antiplatelet benefits clearly outweigh bleeding risks in secondary prevention, its role in primary prevention is far narrower, with a 0.4% absolute reduction in events virtually canceled out by a 0.4% risk of bleeding, Gallagher explained. Whether that delicate balance shifts in patients with CKD -- a population that has both a higher cardiovascular burden and heightened bleeding risks -- had yet to be formally evaluated.
To address this gap, Gallagher and colleagues conducted the pragmatic, multicenter, open-label ATTACK trial, the first study of significant scale designed to answer the question.
The trial randomized 4,633 participants from primary care practices: 2,317 to daily aspirin 75 mg and 2,316 to no aspirin, both alongside usual care. Outcomes were tracked using routinely collected hospital data.
Enrolled participants had stage 1 to 4 CKD, no established cardiovascular disease, and no elevated bleeding risk, and were not taking antiplatelet or anticoagulant medications at baseline. Nearly all participants were white, with a mean age of 73 and a mean estimated glomerular filtration rate of 54 mL/min/1.73 m².
There were no statistically significant differences in secondary outcomes, including all-cause mortality, major hemorrhage, or site-specific bleeding events (intracranial, gastrointestinal, or non-gastrointestinal).
The study ultimately enrolled far fewer participants than its planned target of 25,000 due to pandemic-related disruptions, Gallagher acknowledged. "I think we too have to be very careful about drawing any major conclusions from this work. We're in the process of working with a group called the Antithrombotic Trialists' Collaboration to pool our work and produce an [individual participant data] meta-analysis, which will hopefully answer the question."