ATTACK: Should Patients With CKD Start Aspirin for Primary Prevention?

Whether adults with chronic kidney disease (CKD) and no history of cardiovascular disease (CVD) should take low-dose aspirin to prevent a first heart attack or stroke remains unresolved, after the ATTACK trial found no statistically significant reduction in major cardiovascular events.¹

Presented at the American Society of Nephrology (ASN) Kidney Week 2026 in Denver, Colorado, by Hugh Gallagher, MBBS, PhD, the data come from a pragmatic, open-label, randomized trial conducted in UK primary care. Investigators say pooled analyses with other trials will be needed before aspirin can be recommended for primary prevention in this population.³

CKD is strongly associated with CVD. In the general population, aspirin for primary prevention reduces atherosclerotic vascular events but increases bleeding, and the balance of benefits and harms in people with CKD has been unclear.¹ In patients with established CVD, the benefits of aspirin outweigh its bleeding risk. In lower-risk primary prevention populations, the benefits are largely offset by bleeding.²

“People with CKD are at very high cardiovascular risk,” Gallagher, a consultant nephrologist at Epsom and St Helier University Hospitals NHS Trust and visiting professor at the University of Southampton, said in an interview with HCPLive. “So the question came up: Would they behave a little bit more like the secondary prevention population than the primary prevention population? Would the benefits outweigh the risks?”

Previous evidence on aspirin for primary prevention in CKD came largely from subgroups of general-population trials, which enrolled relatively few people with CKD.² ATTACK was designed as the first definitive randomized trial of aspirin for primary prevention in people with CKD, following a research recommendation from the UK’s National Institute for Health and Care Excellence (NICE).²

How ATTACK Tested Aspirin Through UK Primary Care Records

Investigators recruited adults with CKD stages G1 to G4 and no history of CVD through primary care practices across the UK. Participants were randomly assigned to aspirin 75 mg once daily or no aspirin in an open-label design, and the trial was powered for a sample size of 25,210.¹

Gallagher explained that the trial relied on routinely collected data. Automated searches of coded primary care records identified potentially eligible patients, practices sent the invitations, and interested patients responded to the central study team.

The primary outcome was time to first major cardiovascular event: nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death, excluding intracranial hemorrhage and other fatal cardiovascular bleeding. Secondary outcomes included time to first major bleed and all-cause mortality.¹

COVID-19 Pandemic Limited ATTACK Enrollment to 4633 Participants

“We wanted 25,000, and we ended up with 4633, which is still a lot,” Gallagher said. “But it was not as many as we hoped, and obviously that reduced the power of the study to demonstrate a difference.”

The trial was paused in March 2020 and restarted in March 2021 with fully remote procedures, requiring no face-to-face contact.² Gallagher said the pandemic hit UK primary care hard, and enrollment never returned to its original pace because general practitioners had less capacity for work outside core clinical care. He added that the trial had been powered to detect a relatively small effect, closer to what would be expected in a general primary prevention population.

Aspirin Results for Major Cardiovascular Events and Bleeding in CKD

Between March 2019 and December 2023, 4633 participants were randomized, 2317 to aspirin and 2316 to control, and followed for a mean of 3.1 years.¹

The primary outcome occurred in 56 participants (2.4%) in the aspirin arm and 76 (3.3%) in the no-aspirin arm. The subdistribution hazard ratio (SHR) was 0.73 (95% CI, 0.52 to 1.03).

There were 29 major bleeding events in the aspirin arm, including 10 intracranial, vs 19 in the no-aspirin arm, including 9 intracranial (SHR, 1.54; 95% CI, 0.86 to 2.74). Deaths occurred in 124 participants (5.4%) in the aspirin arm and 113 (4.9%) in the no-aspirin arm (HR, 1.11; 95% CI, 0.86 to 1.43).¹

Investigators described the 27% reduction in the primary outcome as clinically meaningful but not statistically significant. They noted that the trial enrolled fewer participants than planned, which reduced its ability to detect a difference, and that the findings are also consistent with no effect.¹ Gallagher said the team is not recommending aspirin for primary prevention in people with CKD on the basis of these results. Beyond the reduced sample size, the open-label design is a consideration when interpreting the findings.

Net Clinical Benefit and Pooled Aspirin Data Next for CKD

“What you really want to get overall is some kind of idea of a net clinical benefit, and there’s probably a bit more to that than just adding up the number of cardiovascular events and subtracting the number of bleeds,” Gallagher said.

Cardiovascular events and bleeds may not carry equal weight for patients, he noted, and the team hopes to add quality-of-life data to the analysis. The investigators are also working with the Antithrombotic Trialists’ Collaboration to combine ATTACK results with data from previous studies. Their goal is a more definitive estimate of the balance of benefits and harms.³

Editor’s Note: ATTACK was funded by the National Institute for Health Research and the British Heart Foundation. Gallagher reported no relevant disclosures.

References

1. Gallagher H, Dumbleton JS, Daunt W, et al. ATTACK (Aspirin To Target Arterial events in Chronic Kidney Disease): a multicentre randomised trial of aspirin vs. usual care for the primary prevention of cardiovascular events in patients with CKD. Abstract presented at: American Society of Nephrology Kidney Week 2026; October 22–25, 2026; Denver, CO. Abstract FR-OR100. doi:10.1681/ASN.2026pd5vw8fa

2. Gallagher H, Dumbleton J, Maishman T, et al. Aspirin to target arterial events in chronic kidney disease (ATTACK): study protocol for a multicentre, prospective, randomised, open-label, blinded endpoint, parallel group trial of low-dose aspirin vs. standard care for the primary prevention of cardiovascular disease in people with chronic kidney disease. Trials. 2022;23:331. doi:10.1186/s13063-022-06132-z

3. American Society of Nephrology. Late breaking, high-impact clinical trials featured at Kidney Week 2026 explore new frontiers to improve kidney health. Published October 22, 2026. Accessed October 23, 2026. https://www.asn-online.org/about/press/releases/ASN_PR_20261023_2026KidneyWeekTrial.pdf