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.