Therapeutic sequencing in cardiovascular-kidney-metabolic syndrome: a stage- and phenotype-based approach

Cardiovascular-kidney-metabolic (CKM) syndrome refers to the intertwined effects of increased adiposity, metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). Although many therapies have been developed for the management of cardiovascular, kidney, and metabolic diseases, recommendations for their use are distributed across separate disease-specific guidelines. The clinician needs to decide on the order of initiation of therapies, whether therapies can be taken together, and how the order of initiation changes based on the stage of CKM, predominant phenotype, level of renal function, presence of albuminuria, hypertension, hyperkalemia, congestion, obesity, drug tolerance, treatment access, and feasibility. This review suggests a stage- and phenotype-oriented therapeutic sequence across CKM conditions. It includes lifestyle and obesity therapy, renin-angiotensin system (RAS) inhibition, sodium-glucose cotransporter-2 inhibition, mineralocorticoid receptor antagonism, incretin therapies, heart failure drugs, hypertension management, and lipid-lowering therapies.