Aspirin does not reduce CVD events, progression to kidney failure in patients with CKD
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Among patients with chronic kidney disease, aspirin use did not correlate with reduced risks for CVD, progression to kidney failure or major bleeding, according to data published in Kidney Medicine.
“Traditionally, aspirin has been recommended in the prevention of primary and secondary cardiovascular disease and death in the general population, and in high-risk groups such as CKD. Recent emerging data suggests a lack of benefit in the primary prevention of CVD and an increased bleeding risk in the general population. To date, many studies exclude CKD patients, who are at higher CVD risk,” Jonathan J. Taliercio, DO, FASN, the program director of nephrology and hypertension fellowship and assistant professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and colleagues wrote.
In a prospective observational cohort, researchers investigated the risks and benefits of aspirin use in primary and secondary prevention of CVD and progression to kidney failure among 3,664 patients with CKD from the Chronic Renal Insufficiency Cohort (CRIC) Study between 2003 and 2018. Additional outcomes that researchers considered included prevention of mortality and major bleeding.
Of the cohort, 70% did not have preexisting CVD and 42% were taking aspirin at study entry. About half of patients reported aspirin use at each follow-up.
Researchers conducted intention-to-treat analyses and multivariable Cox proportional hazards model to determine the correlations of time-varying aspirin use.
A total of 2,578 patients were included in the primary prevention group. Mean eGFR was 45 mL/min/1.73 m2, and the median follow-up was 11.5 years. Researchers did not observe a correlation between aspirin usage and all-cause mortality among patients with or those without CVD. Similarly, aspirin did not correspond with a lowered risk of the CVD composite outcome of myocardial infarction, stoke and peripheral arterial disease.
“Despite these findings, we advocate for the use of aspirin in secondary prevention in individuals at low risk of bleeding. We anxiously await the results of the [The Aspirin to Prevent a First Heart Attack or Stroke in People with Chronic Kidney Disease] ATTACK trial to help shed light on aspirin use in CKD patients for primary prevention and hope for more trials to better assess secondary prevention in this highly vulnerable population,” Taliercio and colleagues wrote. They added, “[ATTACK] is actively attempting to recruit 25,210 participants, but results will not be released until 2025.”
Perspective
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Anna Burgner, MD, and Antonette Hernandez, MD
Chronic kidney disease is an epidemic and an independent risk factor for CVD. The high incidence of cardiovascular events (CVE) cannot fully be attributed to traditional risk factors, including hypertension, hyperlipidemia, diabetes or tobacco use. While the pathophysiology of this occurrence is not fully elucidated, kidney-specific risk factors, including vascular calcification, increased inflammation and oxidative stress with subsequent endothelial damage and remodeling of the myocardium, likely play extensive roles. Death from CVE is the number one cause of mortality in patients with CKD, often occurring before the need for dialysis. Despite this well described association, randomized studies on pharmacologic interventions to mitigate CVD have historically excluded patients with CKD, limiting the ability to draw definitive conclusions.
Aspirin significantly reduces subsequent CVE and has become a cornerstone therapy for secondary prevention. It has been adopted by multiple societal guidelines, including Kidney Disease Improving Global Outcomes (KDIGO). This is despite the limited data of its use specifically in patients with CKD. Guidelines for the use of aspirin for primary prevention is less well defined and is currently not recommended in patients with CKD per KDIGO.
The Chronic Renal Insufficiency Cohort (CRIC) phase 1 study dataset consists of a diverse population of almost 4,000 patients with eGFR of 20 mL/min/1.73 m2 to 70 mL/min/1.73 m2 gathered prospectively from seven clinical centers between 2003 and 2018. The purpose of this dataset is to define the risk factors for kidney disease progression and its sequalae, particularly CVD.
The observational study by Taliercio and colleagues investigated the risks and benefits of aspirin for primary and secondary CVD prevention using the CRIC study population. In the intention-to-treat analysis for the primary outcomes of all-cause mortality and CVD, there was no benefit of aspirin in either the primary or secondary prevention groups. Similarly, there was no benefit of aspirin in either group in the secondary outcomes of myocardial infarction, stroke and peripheral artery disease. Furthermore, aspirin was not associated with progression to dialysis, incidence of kidney transplant or increased risk for bleeding.
These negative findings are not surprising. Aspirin has not consistently been associated with a reduction in incident CVE or mortality in patients with CKD based on meta-analyses, CKD subgroup analyses and post hoc analyses of prior studies. The [Aspirin for Primary Prevention of Cardiovascular Disease and Renal Disease Progression in Chronic Kidney Disease Patients] AASER study, the only RCT evaluating aspirin use in patients with CKD, suggested aspirin — while not associated with a reduction in CVD — was associated with a reduction in incident coronary events. These largely negative results may emphasize the unique pathophysiological basis of CVD in CKD that may require other targeted therapies or further delineation on appropriate dosing.
The results of this study do not change current clinical practice. These add to prior hypothesis -generating data, which underscore the need for a large, randomized control trial in patients with CKD. The Aspirin to Prevent a First Heart Attack or Stroke in People with Chronic Kidney Disease (ATTACK) study is randomizing more than25,000 participants with CKD to assess the use of aspirin for primary prevention of CVD and will hopefully settle the issue once and for all.
References:
Taliercio JJ, et al. Kidney Medicine.2022; doi:https://doi.org/10.1016/j.xkme.2022.100547.
Gallagher H et al. Trials. 2022; 1-doi:10.1186/s13063-022-06132-z.
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