Genotype-guided antiplatelet therapy after percutaneous coronary intervention: a systematic review and meta-analysis of randomised controlled trials

Background the clinical benefit of genotype-guided antiplatelet therapy compared with standard treatment in patients undergoing percutaneous coronary intervention (PCI) remains uncertain. We conducted a systematic review and meta-analysis to assess the impact of a genetic testing–guided strategy on ischaemic and safety outcomes after PCI. Methods electronic databases were systematically searched to identify randomised controlled trials comparing genotype-guided versus standard antiplatelet therapy in patients undergoing PCI. After screening the retrieved records, eligible trials were included in a meta-analysis. Pooled effect estimates were calculated as incidence rate ratios (IRRs) with 95% confidence intervals (CIs) using random-effects models. Analyses were performed in the overall population and according to clinical presentation (acute versus chronic coronary syndromes). Results our analysis included 8 randomised controlled trials with data for 10,850 patients. Compared with standard therapy, genotype-guided antiplatelet selection was associated with a significant reduction in major adverse cardiovascular events (MACE) (IRR 0.63, 95% CI 0.43–0.94) and stent thrombosis (IRR 0.64, 95% CI 0.43–0.95). Stroke showed a borderline reduction in the overall population (IRR 0.65, 95% CI 0.41–1.01), reaching statistical significance in the acute coronary syndrome cohort (IRR 0.56, 95% CI 0.33–0.97). No significant differences were observed for all-cause mortality (IRR 0.65, 95% CI 0.31–1.38) or cardiovascular mortality (IRR 0.70, 95% CI 0.40–1.21). Similarly, major bleeding (IRR 0.86, 95% CI 0.63–1.16) and minor bleeding (IRR 0.78, 95% CI 0.56–1.09) did not differ significantly between strategies. Subgroup analyses according to acute or chronic clinical presentation did not reveal significant interactions; however, these analyses were limited by the small number of patients within each subgroup and wide confidence intervals. Conclusions in patients undergoing PCI, a genotype-guided antiplatelet strategy is associated with improved ischaemic outcomes, particularly through reductions in MACE and stent thrombosis, without an excess of bleeding. However, no significant reduction in all-cause or cardiovascular mortality was observed. These findings support a selective role for genetic testing in tailoring antiplatelet therapy, while highlighting the need for adequately powered studies to clarify effects on hard mortality endpoints.