Rapid Clinical Updates: Cardio-Renal-Metabolic Disease and Care Models for Hospital Medicine-Handout

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Cardiorenal-metabolic (CRM) disease encompasses the interconnected spectrum of atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and type 2 diabetes (T2D), which collectively represent major causes of global morbidity and mortality. Approximately 25% of affected individuals suffer from more than one of these conditions. CRM disease progresses through four stages, necessitating comprehensive treatment strategies targeting overlapping pathophysiological mechanisms.<br /><br />Current management rests on four therapeutic pillars: sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), mineralocorticoid receptor antagonists (MRA), and renin-angiotensin system (RAS) inhibitors such as ACE inhibitors or ARBs. Groundbreaking clinical trials have demonstrated that combining these agents yields substantial improvements in both cardiovascular and renal outcomes.<br /><br />Recent advances highlight the safety and efficacy of simultaneous initiation of SGLT2i and nonsteroidal MRAs (nsMRA) in patients with CKD and T2D, notably from the CONFIDENCE trial. The combination of finerenone (an nsMRA) and empagliflozin (an SGLT2i) significantly reduced urinary albumin-to-creatinine ratios beyond monotherapy effects. Additionally, finerenone has been shown to lower the risk of new-onset atrial fibrillation or flutter across the cardiorenal-metabolic spectrum.<br /><br />Hyperkalemia, a frequent side effect, remains a significant challenge. Treatment initiation is contraindicated at potassium levels ≥5.0 mmol/L; ongoing therapy may continue between 4.8-5.5 mmol/L but should be held if potassium exceeds 5.5 mmol/L. Management strategies include reviewing and discontinuing contributory non-RAS medications, employing diuretics, dietary adjustments, bicarbonate therapy, potassium binders, and continued use of SGLT2i. Premature discontinuation due to hyperkalemia is linked to increased cardiovascular risks, indicating the importance of careful monitoring and reinitiation when feasible.<br /><br />In summary, integration of SGLT2 inhibitors, GLP-1 receptor agonists, MRAs, and RAS inhibitors represents a transformative approach in CRM disease care, underpinned by robust clinical trial data demonstrating reduced adverse cardiac and renal outcomes. Ongoing patient monitoring and management of adverse effects like hyperkalemia remain crucial for optimizing long-term benefits.

Keywords

Cardiorenal-metabolic disease

Atherosclerotic cardiovascular disease

Chronic kidney disease

Type 2 diabetes

SGLT2 inhibitors

GLP-1 receptor agonists

Mineralocorticoid receptor antagonists

Renin-angiotensin system inhibitors

Hyperkalemia management

CONFIDENCE trial