Pharmacogenomics-guided personalized therapy for hypertension: a multicenter randomized trial

Abstract

Objective: Uncontrolled hypertension presents a substantial challenge to healthcare systems. This study was designed to investigate whether pharmacogenomics-guided personalized medication regimens could enhance blood pressure control and medication optimization in patients with hypertension compared to conventional management approaches.

Methods: In this multicenter, single-blind, prospective, randomized controlled trial, 776 hypertensive outpatients were enrolled and allocated to either a personalized medication group or a control group across eight participating hospitals. All patients received 4 weeks of standardized hypertension management, followed by a first follow-up. Subsequently, the personalized medication group adjusted antihypertensive therapy according to seven predefined pharmacogenetic polymorphisms, while the control group continued standard treatment. After an additional 4 weeks, a second follow-up was performed to reassess blood pressure, medication utilization, and adverse events.

Results: The personalized medication group achieved a notably higher blood pressure control rate compared to the control group, with female patients demonstrating particularly pronounced benefits. Additionally, the personalized medication group required fewer antihypertensive medications. The incidence of adverse events, including reactions to angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, β-blockers, calcium channel blockers, and diuretics, did not differ significantly between groups. Multifactorial analysis indicated that personalized medication significantly lowered the risk of uncontrolled blood pressure. Furthermore, the CYP2C9*3 gene variant was associated with uncontrolled blood pressure after standardized treatment.

Conclusion: Pharmacogenomics-guided personalized medication regimens significantly improved blood pressure control and optimized medication usage without increasing adverse events. These findings highlight the potential of pharmacogenomics to guide precision therapy in hypertension management.

Trial registration: Chinese Clinical Trial Registry (ChiCTR2200057507). Registered 14 March 2022.

Keywords: blood pressure control; gene polymorphisms; hypertension; personalized medication; pharmacogenomics.