Patients with higher-grade chronic kidney disease (CKD) but no established cardiovascular disease who took daily aspirin showed a 43% cut in the rate of adverse cardiovascular events, with no increase in bleeding, compared with placebo during a median 4.6 years of follow-up.
The finding appears to identify a high-risk population – people with an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 who averaged 67 years old – that bucks the now established advice to not start low-dose aspirin for primary prevention of cardiovascular disease events in people over 59.
Medscape reports that the latest finding, from a post-hoc subgroup analysis of 983 patients with CKD enrolled in the previously reported TIPS-3 trial, confirms two prior reports of secondary analyses, with the results collectively “suggesting that aspirin may moderately reduce the substantial cardiovascular disease risk of people with CKD but no history of cardiovascular disease: primary prevention”, said Dr Johannes Mann on 20 May at the European Renal Association Congress in Paris, France.
Bleeding not a problem
The rates of major, minor and gastrointestinal bleeds in these patients taking a 75-mg/day dose of aspirin were nearly identical to the rate among the placebo patients, showing that, at this dose and in these patients, “bleeding was not a problem”, added Mann, a nephrologist and professor of medicine at the University of Erlangen-Nürnberg in Germany.
The “bleeding risk may not outweigh the cardiovascular disease benefit in patients with CKD,” he concluded. The same finding consistently appeared in secondary analyses previously reported from two other controlled trials, the Hypertension Optimal Treatment trial, and the Aspirin in Reducing Events in the Elderly trial.
“CKD defines, by itself, a high cardiovascular disease risk, and therefore my suggestion is to use aspirin for primary prevention in patients with CKD,” Mann said. More definitive evidence for this benefit may come in results from about 25,000 people enrolled in the ongoing ATTACK trial, with an anticipated completion date in 2025, he added.
The results showed “beautiful efficacy in the CKD population”, commented Dr Ronald Gansevoort, a nephrologist and professor of medicine at University Medical Centre Groningen, The Netherlands.
Primary or secondary prevention in patients with CKD?
“Is this primary prevention in patients with CKD?” asked Gansevoort. “I think that CKD is an ongoing process; everything we do (in these patients) is secondary prevention and that is the reason why they show benefit from aspirin, just as aspirin has shown benefit in all secondary prevention trials. We should not regard CKD as a risk factor; it is the disease.”
Mann countered that, despite having more advanced CKD, with eGFR levels of less than 60 mL/min/1.73m2, the patients in TIPS-3 still represented a primary prevention population by lacking a history of a cardiovascular disease event.
But Mann also agreed that “CKD as a risk equivalent of cardiovascular disease was established consistently in several studies” dating back more than two decades to a report he published in 2001 from the HOPE study.
TIPS-3 enrolled 5,712 middle-aged or elderly adults in any of nine countries without a history of cardiovascular disease but with intermediate or high cardiovascular risk based on their INTERHEART Risk Score. The study prospectively randomised patients in a 2×2 factorial design to aspirin or placebo, or to a “low-dose” polypill or placebo. The polypill included half doses of three different classes of blood pressure- lowering medications, plus 40 mg of simvastatin.
Primary results from TIPS-3
The primary endpoint of TIPS-3, first reported in November 2020, was the combined rate of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure, resuscitated cardiac arrest, and arterial re-vascularisation.
After a median follow-up of 4.6 years, people who took the polypill had a 21% relative reduction in their combined event rate compared with those taking placebo, a difference of borderline significance. Those who received aspirin had a 14% relative risk reduction that was not significant. In an analysis of those who received both active agents compared with those who received neither, the combined regimen linked with a significant 31% relative cut in the combined cardiovascular disease endpoint.
The post-hoc analysis now reported by Mann focused on the 17% of patients with an eGFR of less than 60 mL/min/1.73m2, a subgroup with a 36% prevalence of diabetes and an 84% prevalence of hypertension. In addition to showing a significant 43% relative risk reduction linked with aspirin use in this group, his analysis also showed essentially no effect on the primary endpoint in the remaining study participants with higher levels of renal function.
Hints of an additive polypill and aspirin effect
Preliminary analysis of those with CKD who received both aspirin and the polypill showed evidence of an “additive” effect of the two interventions, said Mann, which together, produced a significant 63% reduction in the primary endpoint, an outcome he said will be the focus of a future report.
Mann also highlighted the cost-effectiveness of aspirin in the CKD subgroup, with an estimated cost of about €2500 to prevent one event. That’s a price tag that’s markedly below the monetary cost of many other agents currently used to prevent cardiovascular disease events, he noted.
Medscape article – Aspirin Links With CVD Cut in Patients With Kidney Disease (Open access)
See more from MedicalBrief archives:
Polypill plus aspirin reduces incidence of cardiovascular events by 31% — TIPS-3
Large trial produces ‘best evidence’ of aspirin benefits in reducing CVD risk
Daily 4-in-1 polypill could cut CVD risk in low-income countries