Pharmacogenomics-guided therapy for essential hypertension: a multi-center randomized controlled open-label trial

Abstract

Background The advent of pharmacogenomics-guided antihypertensive therapy represents a paradigm shift in hypertension management. This study aimed to investigate the prevalence of relevant genetic variants among hypertensive patients in Hunan Province, China, and evaluate the efficacy of genotype-directed vs. clinically guided therapy. Methods A total of 2,702 patients with essential hypertension from 14 hospitals were enrolled and evenly randomized to either a control group receiving standard care or an experimental group receiving pharmacogenomics-tailored medication. Genetic variants in seven gene loci (ADRB1, CYP2D6, CYP3A5, CACNA1C, CYP2C9, ACE, ADD1) associated with five major drug classes were analyzed. Blood pressure and biochemical parameters were assessed at baseline and 4 weeks post-intervention. Results The frequencies of the risk allele frequencies for ACE, CYP2C9, ADRB1, CYP2D6, CYP3A5, CACNA1C, and ADD1 were 34.3%, 4.8%, 74.8%, 57.3%, 69.8%, 11.9%, and 46.3%, respectively. After 4 weeks, blood pressure significantly decreased in both groups (all P < 0.001), with a more pronounced reduction observed in the experimental group (from 155.45/92.12 mmHg to 129.03/76.96 mmHg) compared to the control group (from 156.52/91.75 mmHg to 143.74/82.73 mmHg). The genotype-guided group also achieved a significantly higher blood pressure control rate. Conclusion These findings highlight the critical role of genetic profiling in antihypertensive drug selection. Personalized treatment based on pharmacogenomics offers a more effective strategy for hypertension management. In the studied Hunan population, angiotensin II receptor blockers and beta-blockers emerged as particularly efficacious options under genotype guidance.