Cost-Effectiveness of Pharmacogenomics-Guided Treatment in Cardiovascular Disease: An Umbrella Review

Background Pharmacogenomics-guided prescribing uses patient genetic information to individualize drug selection and dosing and has attracted interest as a strategy to improve outcomes and reduce adverse drug events in cardiovascular diseases. Several systematic reviews have examined its cost-effectiveness, but their findings have not been synthesized across drug classes and healthcare settings. Objective To identify, critically appraise, and synthesize findings from systematic reviews evaluating cost-effectiveness or cost-utility of pharmacogenomics-guided treatment of cardiovascular diseases. Methods This systematic review of systematic reviews was pre-registered in PROSPERO (CRD420261281565). Five databases were searched from inception, without language restrictions. Eligible studies were systematic reviews that summarized cost-effectiveness evidence on pharmacogenomics-guided cardiovascular drug prescribing. Risk of bias was assessed using ROBIS and methodological quality using AMSTAR 2. Findings were synthesized narratively. Results Ten systematic reviews (2010–2024) were included, encompassing 149 unique primary cost-effectiveness studies. The corrected covered area across reviews was 9.47% (moderate overlap). Most evidence was derived from economic modelling studies and substantial heterogeneity was observed across drug–gene pairs, comparators, and healthcare settings. CYP2C19-guided clopidogrel therapy was frequently reported as cost-effective or cost-saving, although results were less favourable when universal ticagrelor served as comparator. Evidence for CYP2C9/VKORC1-guided coumarin anticoagulation was more heterogeneous with cost-effectiveness varying across contexts. Limited evidence suggested that SLCO1B1-guided statin therapy may be cost-effective, although data were sparse. No review reported pooled incremental cost-effectiveness ratios or net monetary benefit. Risk of bias was low in 7 reviews; AMSTAR 2 confidence was high in 4 and low in 5. Conclusion Cost-effectiveness of pharmacogenomics-guided cardiovascular treatment seems to vary by drug–gene pair, comparator, healthcare context, and modelling assumptions. Further real-world studies and standardized economic evaluations are needed to clarify broader clinical adoption.