A Pilot Randomized Study of NAT2 and YEATS4 Pharmacogenetic Return of Results in Adults with Hypertension and African Ancestry: The GUARDD-US PGx Study.

@article{empey2026pilot,
  title = {{A Pilot Randomized Study of NAT2 and YEATS4 Pharmacogenetic Return of Results in Adults with Hypertension and African Ancestry: The GUARDD-US PGx Study.}},
  author = {Philip E Empey and Nita A Limdi and Dinushika Mohottige and Kady-Ann Steen-Burrell and Hrishikesh Chakraborty and Khoa A Nguyen and Alexander S Parker and Emily J Cicali and Girish N Nadkarni and Michelle A Ramos and Sabrina Clermont and Erica N Elwood and Mimsie Robinson and Nandini Shroff and Marc B Rosenman and Ronald Huang and Larisa H Cavallari and Julie A Johnson and Paul R Dexter and Todd C Skaar and Kerri L Cavanaugh and Christina M Wyatt and Carol R Horowitz and Rhonda M Cooper-DeHoff and Michael T Eadon and IGNITE Pragmatic Trials Network},
  journal = {Clinical pharmacology and therapeutics},
  year = {2026},
  month = oct,
  doi = {10.1002/cpt.70527},
  url = {https://europepmc.org/article/MED/42894271},
  note = {CC BY},
}

TY  - JOUR
TI  - A Pilot Randomized Study of NAT2 and YEATS4 Pharmacogenetic Return of Results in Adults with Hypertension and African Ancestry: The GUARDD-US PGx Study.
AU  - Philip E Empey
AU  - Nita A Limdi
AU  - Dinushika Mohottige
AU  - Kady-Ann Steen-Burrell
AU  - Hrishikesh Chakraborty
AU  - Khoa A Nguyen
AU  - Alexander S Parker
AU  - Emily J Cicali
AU  - Girish N Nadkarni
AU  - Michelle A Ramos
AU  - Sabrina Clermont
AU  - Erica N Elwood
AU  - Mimsie Robinson
AU  - Nandini Shroff
AU  - Marc B Rosenman
AU  - Ronald Huang
AU  - Larisa H Cavallari
AU  - Julie A Johnson
AU  - Paul R Dexter
AU  - Todd C Skaar
AU  - Kerri L Cavanaugh
AU  - Christina M Wyatt
AU  - Carol R Horowitz
AU  - Rhonda M Cooper-DeHoff
AU  - Michael T Eadon
AU  - IGNITE Pragmatic Trials Network
PY  - 2026
DA  - 2026/10/18
JO  - Clinical pharmacology and therapeutics
DO  - 10.1002/cpt.70527
UR  - https://europepmc.org/article/MED/42894271
AB  - Almost half of individuals with hypertension fail to achieve recommended blood pressure (BP) goals. Pharmacogenetic gene-drug interactions may alter the efficacy of antihypertensive agents. We conducted a multicenter randomized controlled sub-study of participants (N = 1874) with hypertension and self-reported African ancestry to determine whether pharmacogenetic return of results (RoR) would improve systolic blood pressure (SBP) at 3 months. Participants were randomized to immediate pharmacogenetic RoR (intervention) or delayed RoR at trial completion (control). Clinical decision support conveyed recommendations for YEATS4-guided thiazide diuretic selection and NAT2-guided hydralazine dosing. Prespecified subgroup analyses included those with uncontrolled BP (baseline SBP ≥140 or DBP ≥90 mm Hg) and actionable genotypes. Immediate RoR did not improve SBP at 3 months in a broad population of hypertensive adults with controlled and uncontrolled SBP (covariate-adjusted change in SBP between groups: -0.3 ± 0.74 mm Hg, 95% CI: -1.8, 1.2). In participants with an actionable YEATS4 genotype (N = 867) predicting reduced thiazide efficacy, immediate RoR led to greater SBP reduction at 3 months (-2.46 mm Hg, 95% CI: -4.57 to -0.36). In participants with uncontrolled hypertension at baseline (N = 659), immediate RoR led to a greater reduction in SBP (-2.9 ± 0.74 mm Hg, 95% CI: -5.6, -0.3). Although no SBP reduction was observed in the whole cohort, participants with an actionable YEATS4 genotype or uncontrolled BP who received immediate RoR had a significantly greater SBP improvement than those with delayed RoR. Future studies of antihypertensive pharmacogenetics should recruit individuals with uncontrolled BP and actionable genotypes.
SN  - 0009-9236
SN  - 1532-6535
ER  -