Pharmacogenomics-guided cardiovascular therapy in low- and middle-income countries: A systematic review of barriers, equity gaps, and pathways to personalized medicine

Publisher abstract

Cardiovascular disease causes more deaths than any other condition worldwide, and four in five of these deaths occur in low- and middle-income countries (LMICs). Pharmacogenomics (PGx) uses genetic testing to guide drug selection and administration, which can reduce adverse drug reactions and enhance treatment response; however, LMIC groups are significantly underrepresented in the evidence base, limiting equitable clinical translation. A systematic review was conducted, following PRISMA 2020 guidance, mapping PGx-guided cardiovascular therapy, implementation barriers, and equity gaps in LMICs. PubMed and Scopus were searched for studies published between January 2020 and December 2025 and included 24 studies (one randomized controlled trial, 19 observational studies, and four economic models); because of substantial clinical and methodological heterogeneity, findings were combined through SWIM guidelines, and certainty of evidence was assessed using GRADE. Genotype-guided warfarin dosing nearly quintupled the time patients spent in the therapeutic INR range compared with standard care, and decision-analytic models supported the cost-effectiveness of genotype-guided antiplatelet therapy. Ancestry-specific genetic variants relevant to heart-failure drug response, statin-induced myotoxicity, and resistant hypertension were identified, yet African-ancestry individuals made up less than 1% of global PGx study participants. The certainty of evidence varied from very low to moderate across outcomes, indicating a near-total dependence on observational designs and small sample sizes. High testing prices, workforce shortages, low physician genetic knowledge, and the lack of locally appropriate prescribing recommendations all remain obstacles to implementation. Based on these findings, a four-tiered, health-system-focused implementation approach is proposed that spans primary care to national policy. To create regionally calibrated prescribing guidelines in LMICs, multi-site randomized trials, ancestry-informed genomic data, and coordinated policy investment are required.