Abstract 4367431: Impact of Genetic Polymorphism on Antihypertensive Drug Response: Comparing ACE Inhibitors and ARBs – A Systematic Review and Meta-Analysis

Background: Pharmacogenomics is increasingly recognized as a key factor in optimizing antihypertensive therapy. Genetic polymorphisms may influence individual responses to commonly prescribed antihypertensives, particularly angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). This systematic review and meta-analysis evaluates the impact of genetic variants on the antihypertensive efficacy of ACEIs versus ARBs in adults. Methods: A systematic search was conducted across published meta-analyses and systematic reviews written in English, focusing on adult populations (≥18 years) treated with ACEIs or ARBs. Studies were included if they examined the influence of genetic polymorphisms—such as those in the ADRB2, AGT, ACE, or CYP11B2 genes—on blood pressure response. Eligible studies compared ACEIs and ARBs directly or within the context of genetic stratification. Data were extracted on gene-drug interactions, blood pressure outcomes, and methodological quality. Results: A forest plot was generated to visually summarize genotype-specific differences in blood pressure response to ACE inhibitors versus ARBs. Several polymorphisms were consistently associated with differential responses to RAAS-targeting therapies. ACEI efficacy was particularly influenced by the I/D polymorphism in the ACE gene, while M235T variants in the AGT gene and -344T/C in CYP11B2 impacted ARB response. Polymorphisms in ADRB2, such as rs1042713, were also linked to differential outcomes. ARBs demonstrated more consistent blood pressure reductions across genetic backgrounds, while ACEIs showed greater variability. Studies suggest that pharmacogenetic-guided therapy may improve treatment precision and clinical outcomes. Conclusions: Genetic polymorphisms significantly influence antihypertensive responses, with ACEIs showing more genotype-dependent effects. ARBs may offer a more predictable therapeutic profile in genetically diverse populations. These findings support the integration of pharmacogenomic testing into hypertension management to enable individualized therapy.