A randomized trial of genotype-guided perindopril use

Area of Science:

• Pharmacogenomics
• Cardiovascular Medicine
• Genetics

Background:

• Angiotensin-converting enzyme inhibitors (ACEIs) are crucial for hypertension management but often cause dose-limiting cough.
• This side effect restricts their clinical utility and potential cardiovascular benefits.
• Personalized medicine approaches are needed to mitigate ACEI-induced cough.

Purpose of the Study:

• To investigate if genotype-guided perindopril use could reduce drug-related cough in hypertensive individuals.
• To assess the efficacy of NELL1 variant data in guiding renin-angiotensin system blocker selection.

Main Methods:

• A randomized trial involving 68 hypertensive patients (20-79 years old) assigned to genotyping or control groups.
• The genotyping group used NELL1 p.Arg382Trp and intron genotypes to guide treatment: candesartan for high-risk, perindopril for low-risk.
• The control group received perindopril without genotyping.

Main Results:

• The genotyping group had significantly lower risks of cough (12.2% vs 33.3%) and moderate/severe cough (2.4% vs 18.5%) compared to the control group.
• Hazard ratios for cough and moderate/severe cough were 0.25 (P=0.017) and 0.12 (P=0.025), respectively.
• Adverse event rates were similar across all groups.

Conclusions:

• Genotype-guided treatment significantly reduced the incidence of cough compared to conventional treatment.
• NELL1 variant data is valuable for personalizing renin-angiotensin system blocker therapy, improving patient outcomes.
• This strategy enhances the safe and effective use of antihypertensive medications.