Pharmacometabolomics of treatment response to antihypertensive drugs: a systematic review

Hypertension remains a prevalent, modifiable risk factor for cardiovascular disease, with many patients failing to achieve optimal blood pressure (BP) control despite existing therapies. Pharmacometabolomics offers promise by identifying metabolic biomarkers linked to drug response and holds potential for individualizing antihypertensive treatment. We conducted a systematic review of studies from 2013 to 2023, screening 2577 articles and including five that investigated metabolomics-based biomarkers for antihypertensive drug response in cases of primary hypertension. In total, 46 metabolites were significantly associated with BP responses to diuretics, beta-blockers, and ACE inhibitors or angiotensin receptor blockers. Key predictive metabolites included arachidonic acid, sphingosine-1-phosphate, 2-oxoglutarate, and arachidonoyl-carnitine, affecting responses across fatty acid metabolism, sphingolipid metabolism, the TCA cycle, and amino acid metabolism. This review highlights the potential of pharmacometabolomics to uncover metabolites and pathways associated with individual BP response to antihypertensive drugs. Further validation in diverse populations, drug classes, and combination treatments is needed.