To investigate the distribution patterns of pharmacogenomic characteristics in hypertensive patients treated and to evaluate the differential benefits of genotype-guided therapy in calcium channel blocker (CCB) strategy versus beta-blocker strategy.

In the first phase, pharmacogenomic data of patients with primary hypertension treated at our hospital were analyzed. In the second phase, treatment-naive hypertensive patients were enrolled and randomly assigned in a 1∶1∶1∶1 ratio to four groups: genotype-guided CCB strategy, standard CCB strategy, genotype-guided beta-blocker strategy, and standard beta-blocker strategy. Seven key pharmacogenomic loci, including adrenergic beta-1 receptor (ADRB1) rs1801253 (1165G>C) and cytochrome P450 3A5 (CYP3A5) rs776746, were genotyped using polymerase chain reaction (PCR)-melting curve method. Primary outcomes included time to blood pressure control, incidence of treatment-related adverse events (TRAEs), and length of hospital stay.

In the retrospective phase, 2 783 patients were enrolled. The C allele frequency of ADRB1 rs1801253 was 76.02% (4 231 cases/5 566 cases), and the G allele frequency of CYP3A5*3 was 72.97% (4 062 cases/5 566 cases). In the prospective phase, 300 patients were enrolled. The genotype-guided therapy significantly shortened time to blood pressure control (mean difference: -2.10 days, 95% confidence interval (CI): -2.80 to -1.40, P<0.001), with a significant interaction between therapy approach and treatment strategy (P<0.05). Specifically, in the CCB strategy, genotype-guided therapy reduced control time by 3.20 days (95% CI: -4.10 to -2.30) versus standard therapy, whereas in the beta-blocker strategy, the reduction was only 0.90 days (95% CI: -1.70 to -0.10). Genotype-guided therapy also significantly lowered TRAEs incidence [12.67% (19 cases/150 cases) vs. 25.33% (38 cases/150 cases), P<0.001].

Hypertensive patients at our hospital exhibited a distinct pharmacogenomic profile. Genotype-guided therapy demonstrates substantially greater clinical benefits when applied to CCB strategy than to beta-blocker strategy, providing robust evidence for precision hypertension management within this single-center clinical setting.