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

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.