Debating the Usefulness of ACE/ARBs in Kidney & Cardiovascular Disease with Matthew Weir, MD

At the 9th Annual Heart in Diabetes Conference in Philadelphia, PA, Matthew Weir, MD, professor and director of the division of nephrology at the University of Maryland School of Medicine, presented his analysis of the role that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) can still play in the modern cardiorenal treatment and kidney disease landscapes.

According to the Kidney Disease: Improving Global Outcomes (KDIGO) 2024 guidelines, ACE inhibitors or ARBs are strongly recommended for patients with chronic kidney disease (CKD). Additionally, ACE inhibitors are strongly encouraged for patients with moderate-to-severe albuminuria with diabetes and those with CKD and increased albuminuria regardless of diabetes status.2

Cardiorenal protective measures have always involved multiple drugs, typically including some form of generic angiotensin blocker such as ACE/ARBs. However, these drugs are being prescribed less and less often as more current medications are pushed to the forefront, including glucagon-like peptide-1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and mineralocorticoid receptor agonists (MRAs).1

Weir posits that changes in serum creatinine and serum potassium lead clinicians to avoid ACE/ARB medications, especially in guideline-based doses. However, Weir also makes the point that the medical field has had the means to combat these changes for some time.

“I don’t disagree that there are going to be subtle changes in serum potassium and serum creatinine, but we also know how to medically manage those, and we know how to look for other factors that may be causing these problems to occur,” Weir told HCPLive. “So, from that standpoint, clinicians should be aware of some of the interactions with other medicines we’re using so as to avoid some of the pitfalls of using an ACE or an ARB appropriately in clinical practice.”

Additionally, despite their history of efficacy and safety in treating diabetic kidney disease and heart failure, Weir indicates that significant numbers of patients with either disease are not receiving these medications.

“The fact of the matter is, if you look at published data in the US of people with established diabetic kidney disease, less than half are receiving these drugs,” Weir said. “And of those, less than half are receiving them in doses that have been defined to be kidney protective in clinical trials.”

Additionally, Weir’s presentation indicated that lower doses of ACE/ARB have never been shown to be effective in slowing kidney disease progression. Traditionally, the highest tolerated doses have been consistently recommended in preventing mortality and morbidity in cardiovascular diseases, as well as for patients with diabetes, hypertension, CKD, and albuminuria.1

Weir also acknowledged the possibility that, with newer medications showing the same or better treatment outcomes, ACE and ARBs may be overcomplicating treatment.

“In all of the trials with these drugs showing benefit, the patients have been receiving the highest tolerated dose of an ACE or an ARB, which in the real world is probably less or none,” Weir said. “And so more likely than not, these drugs are going to be every bit as effective with or without an ACE or an ARB. So, in a sense, the ACE and the ARB, as important as they are, maybe in a sense are cluttering the medication list.”

To that end, Weir poses the question of whether ACE/ARBs are necessary in the face of modern treatments such as MRA, which are very effective in anti-atherosclerotic heart failure and kidney disease.

“So, one of the questions I would ask is, would we be able to use MRA more effectively without the background of an ACE or an ARB, even in low dose, in our patients?” Weir said. “Because I suspect they may be a lot more effective in dealing with some of the forms of high blood pressure that we see, the proteinuria that we see in patients with chronic kidney disease.”

Weir makes the following disclosures: AstraZeneca, Bayer, Corcept, CSL Vifor, Boehringer-Ingelheim, NovoNordisk, Mineralys, Vera

References

1. Weir M. Do ACEI/ARB still have a role in the era of SGLT2i, MRA and GLP-1RA? Presented at the 9th Annual Heart in Diabetes Conference in Philadelphia, PA, June 6-8, 2025.

2. Stevens PE, Ahmed SB, Carrero JJ, et al. KDIGO 2024 clinical practice guideline for the Evaluation and management of chronic kidney disease. Kidney International. 2024;105(4). doi:10.1016/j.kint.2023.10.018