Although pharmacogenomics can effectively guide antihypertensive treatment, relevant evidence from low-resource primary care settings is lacking. The aim of this study is to evaluate a pharmacogenomic-guided antihypertensive strategy in real-world, low-resource primary care settings.

We randomly assigned 94 villages (in 1:1:1 ratio, with stratification by villages) to receive a multifaceted intervention that included follow‐up, health education, and medication adjustment guided by pharmacogenomics (treatment) or physician's experience (control), or routine care (observation) over 4 weeks. The primary outcome was the proportion of patients with controlled blood pressure after 4 weeks of treatment. Generalized linear, linear mixed‐effect regression, and sensitivity analysis were conducted to assess the difference among groups. The intracluster correlation coefficient was calculated to assess the heterogeneity with cluster.

This study included 1031 hypertensive patients from 90 villages of Dajie and Jiuzhi towns in Daming County from May 10 to December 31, 2022. Overall, 79 loci on 39 antihypertensive‐related genes were tested for patients in the treatment group. After 4 weeks of treatment, 371 of 377 (98.4%) patients in the treatment group, 256 of 345 (74.2%) patients in the control group, and 232 of 309 (75.1%) patients in the observation group had their blood pressure under control. The between‐group net differences were 24.2% (95% confidence interval [CI]: 19.4%–29.0%) and 23.3% (95% CI: 18.3%–28.3%) for the treatment versus control groups and treatment versus observation groups, respectively. After 4 weeks of treatment, the proportion of patients with overall incident adverse events was no different among the three groups (all p > 0.05), and no serious adverse events or deaths related to antihypertensive treatment were reported during the study period.

A pharmacogenomic‐guided antihypertensive strategy can significantly enhance blood pressure control while maintaining a similar safety level compared to an experience‐guided antihypertensive strategy in low‐resource, primary care settings.