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A randomized trial of genotype-guided perindopril use

 Sang-Hak Lee  ;  Chan Joo Lee  ;  Yura Kang  ;  Jung Mi Park  ;  Ji Hyun Lee 
 JOURNAL OF HYPERTENSION, Vol.41(11) : 1768-1774, 2023-11 
Journal Title
Issue Date
Adult ; Aged ; Angiotensin-Converting Enzyme Inhibitors / adverse effects ; Cough / chemically induced ; Cough / drug therapy ; Cough / genetics ; Genotype ; Humans ; Hypertension* / chemically induced ; Hypertension* / drug therapy ; Hypertension* / genetics ; Middle Aged ; Perindopril* / adverse effects ; Young Adult
Objective: Cough caused by angiotensin-converting enzyme inhibitors (ACEIs) limits their clinical application and cardiovascular benefits. This randomized trial investigated whether genotype-guided perindopril use could reduce drug-related cough in 20 to 79-year-old individuals with hypertension.

Methods: After screening 120 patients and randomization, 68 were assigned to genotyping ( n = 41) and control ( n = 27) groups. NELL1 p.Arg382Trp (rs8176786) and intron (rs10766756) genotype information was used to subdivide the genotyping group into high-risk and low-risk subgroups with at least one or no risk alleles for ACEI-related cough, respectively. The high-risk subgroup received candesartan (8 mg/day) for 6 weeks, whereas the low-risk subgroup received perindopril (4 mg/day). The control group, which was not genotyped, received perindopril (4 mg/day). The primary outcome variables were cough and moderate/severe cough; the secondary outcome variable was any adverse event.

Results: During the 6-week period, the risk of cough was lower in the genotyping group than in the control group [five (12.2%) and nine (33.3%) participants, respectively; hazard ratio: 0.25; log-rank P = 0.017]. The moderate/severe cough risk was also lower in the genotyping group [one (2.4%) and five (18.5%) participants, respectively; hazard ratio: 0.12; log-rank P = 0.025]. Differences in cough (hazard ratio: 0.56; log-rank P = 0.32) and moderate/severe cough risk (hazard ratio: 0.26; log-rank P = 0.19) between the low-risk and control groups were not significant. The risk of total adverse events was similar between any two groups.

Conclusion: Cough risk was lower during genotype-guided treatment than during conventional treatment. These results support the utility of NELL1 variant data in clinical decision making to personalize renin-angiotensin system blocker therapy use.

Trial registration: ClinicalTrials.gov number: NCT05535595 (retrospectively registered at September 7, 2022).

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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lee, Sang Hak(이상학) ORCID logo https://orcid.org/0000-0002-4535-3745
Lee, Chan Joo(이찬주) ORCID logo https://orcid.org/0000-0002-8756-409X
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