What to do with key cardiovascular drugs when kidney function worsens?

Patients with advanced cardiovascular kidney metabolic syndrome generally face a high risk of cardiovascular complications. Guideline-directed medical therapies (GDMT) are critical for mitigating cardiovascular risk and improving prognosis. However, patients with more advanced kidney disease have frequently been excluded from the foundational cardiovascular outcome trials, leaving clinicians with a paucity of evidence with regards to the cardiovascular benefits and potential risks involved in initiating or maintaining GDMT for cardiovascular diseases in patients with chronic kidney disease stages 4 and 5. Numerous studies have demonstrated a systematic underutilization of GDMT among patients with advanced chronic kidney disease (CKD), likely caused by a combination of clinical inertia and a legitimate fear of potential side-effects such as hyperkalemia and rises in creatinine, which may necessitate repeat laboratory monitoring, dose adjustment, and additional potassium-lowering treatment. In this clinical review, we aim to summarize the accumulating evidence with regards to the use of key cardiovascular drugs among patients with advanced CKD, with an emphasis on GDMT in patients with heart failure, and outline the treatment approach used in our integrated heart-nephrology-diabetes clinic. Since the evidence is not always clear and our patients are generally both older, frailer, and have more multimorbidity than those included in clinical trials, sound clinical judgment, individual patient tolerability as well as shared decision-making are key. We also address the need to continuously align treatment goals with patient preferences across different phases of life and adjusting GDMT in the face of increasing frailty.