Preventing Cardiovascular-Kidney-Metabolic Syndrome Progression: Pharmacologic Approaches and Pharmacists' Contributions.

backgroundCardiovascular-kidney-metabolic (CKM) syndrome is a condition reflecting the interactions among metabolic dysfunction, chronic kidney disease (CKD), and cardiovascular disease. It is driven by excess adipose tissue, insulin resistance, inflammation, and vascular and kidney dysfunction, which accelerates the development of hypertension, dyslipidemia, type 2 diabetes, and CKD. Early identification and intervention are critical to prevent progression to advanced cardiovascular and kidney disease; however, optimal interdisciplinary approaches to CKM management are not well established. This narrative review summarizes pharmacotherapeutic strategies to prevent CKM progression for individuals with CKM stages 1 and 2 and the expanding role of pharmacists. SUMMARY: Obesity is a primary driver of CKM syndrome, and early assessment with weight-loss interventions is critical to reduce progression of CKM stages. Management emphasizes lifestyle modification, with pharmacotherapy increasingly used as an adjunct. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual glucose-dependent insulinotropic polypeptide/GLP-1 RAs promote substantial weight loss and provide cardiovascular benefits. Hypertension is an important modifiable risk factor as it contributes to kidney damage and adverse cardiovascular events. Management includes lifestyle modification and antihypertensive therapy with angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), calcium channel blockers, or thiazide diuretics. In patients with albuminuria and CKD, ACEis or ARBs should be prioritized due to their kidney-protective effects. Dyslipidemia contributes to endothelial dysfunction, atherosclerosis, and cardiovascular risk. Statins are first-line therapy, with ezetimibe or PCSK9 inhibitors considered when low-density lipoprotein cholesterol remains above goal despite maximally tolerated statin therapy. Type 2 diabetes and CKD substantially increase the risk of progression to advanced CKM stages. Sodium-glucose cotransporter 2 inhibitors and GLP-1 RAs provide additional cardiovascular and kidney-protective benefits, while ACEis or ARBs remain foundational therapy for slowing CKD progression and reducing CKM risk. Pharmacists play a critical role in early CKM management through medication optimization, patient education, access facilitation, and longitudinal follow-up. Pharmacist-led interventions have been shown to improve blood pressure, lipid levels, glycemic control, weight outcomes, and kidney parameters, supporting prevention of progression to advanced disease stages. KEY MESSAGES: Pharmacotherapy optimization for cardiometabolic and kidney risk factors during CKM stages 1 and 2 is essential to prevent progression to late stage CKM. Although pharmacists are well positioned to participate in comprehensive CKM management, most previous interventions have focused on isolated disease states. Future research should assess the impact of pharmacist-led care on CKM syndrome as an integrated condition to inform patient-centered, multidisciplinary prevention strategies.