Daily Low-Dose Aspirin Did Not Significantly Cut Heart Attacks and Strokes in Kidney Disease Patients, ATTACK Trial Finds

A large randomized trial has failed to show that a daily baby aspirin protects people with chronic kidney disease (CKD) from a first heart attack or stroke. The result was presented at the American Society of Nephrology's Kidney Week in Denver, which ran Oct. 22-25.

The trial is called ATTACK (Aspirin To Target Arterial events in Chronic Kidney Disease). Its lead presenter was Hugh Gallagher, MBBS, PhD, a consultant nephrologist at Epsom and St Helier University Hospitals NHS Trust in England.

What the trial found

Over a mean follow-up of 3.1 years, 2.4% of patients taking aspirin had a major vascular event. That was a composite of non-fatal heart attack, non-fatal stroke, or cardiovascular death. Among patients not taking aspirin, the figure was 3.3%.

The hazard ratio was 0.73 (95% CI 0.52-1.03, P=0.077). The confidence interval crosses 1.0, so the trial missed its primary endpoint.

One component did reach statistical significance. Non-fatal stroke was lower with aspirin (HR 0.51, 95% CI 0.29-0.90, P=0.021). The other components did not reach significance, Gallagher reported.

Gallagher described the overall result as a 27% lower point estimate for cardiovascular events that was not statistically significant.

Who was studied

The pragmatic, open-label trial randomized 4,633 participants through UK primary care practices. Of those, 2,317 got aspirin 75 mg daily and 2,316 got no aspirin, both on top of usual care. Outcomes were tracked through routinely collected hospital data.

Participants had stage 1 to 4 CKD, no established cardiovascular disease, and no elevated bleeding risk. None were taking antiplatelet or anticoagulant drugs at baseline.

The mean age was 73 and the mean estimated glomerular filtration rate was 54 mL/min/1.73 m². Nearly all participants were white.

The trial was powered for a sample size of 25,210 but enrolled 4,633. "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." He attributed the shortfall to pandemic-related disruptions.

Why the question mattered

CKD and cardiovascular disease travel together. Gallagher estimated around 100,000 heart attacks and strokes a year in the U.K. among people with stage 3 to 5 CKD. "Despite this, we still have relatively limited interventions to address this," he said.

In people who already have cardiovascular disease, aspirin's benefit clearly outweighs its bleeding risk. Low-dose aspirin is recommended as secondary prevention for CKD patients with a history of cardiovascular events.

Primary prevention is a much tighter call. In the general population, Gallagher said, aspirin produces a 0.4% absolute reduction in events, which is virtually canceled out by a 0.4% risk of bleeding.

ATTACK tested whether CKD patients, who face higher cardiovascular risk and higher bleeding risk, might tip that balance. "Would they behave a little bit more like the secondary prevention population than the primary prevention population?" Gallagher asked in an interview with HCPLive.

Earlier evidence came mostly from CKD subgroups inside general-population trials, which enrolled relatively few such patients. ATTACK was designed as the first definitive randomized trial in this group, following a research recommendation from the UK's National Institute for Health and Care Excellence (NICE).

What the investigators say now

Gallagher does not read the result as a green light. "We're not in a place where we should be offering aspirin for primary prevention at this stage, but the question still needs answering," he said at the meeting.

He also does not read it as a dead end. The trial's own point estimate leaned toward benefit, and the stroke signal was statistically significant on its own. The investigators say pooled analyses with other trials will be needed before aspirin can be recommended for primary prevention in CKD.

Gallagher also noted the long history of the drug. Aspirin first sold commercially in 1899, he said, "so 130 years later, we're still trying to work out what to do with it." He attributed that to the balance of benefit and harm.

What to watch

For patients with CKD and no cardiovascular history, nothing in ATTACK supports starting aspirin on their own. Anyone already on aspirin after a heart attack or stroke is in the secondary-prevention group, where the recommendation stands.

The open question is whether combining ATTACK with other trials produces a clear answer. The investigators are working with the Antithrombotic Trialists' Collaboration to pool their data into an individual participant data meta-analysis, which Gallagher hopes will answer the question.