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This paper describes the ATHENA Decision Support System (DSS), which operationalizes guidelines for hypertension using the EON architecture. ATHENA DSS encourages blood pressure control and recommends guideline-concordant choice of drug therapy in relation to comorbid diseases. ATHENA DSS has an easily modifiable knowledge base that specifies eligibility criteria, risk stratification, blood pressure targets, relevant comorbid diseases, guideline-recommended drug classes for patients with comorbid disease, preferred drugs within each drug class, and clinical messages. Because evidence for best management of hypertension evolves continually, ATHENA DSS is designed to allow clinical experts to customize the knowledge base to incorporate new evidence or to reflect local interpretations of guideline ambiguities. Together with its database mediator Athenaeum, ATHENA DSS has physical and logical data independence from the legacy Computerized Patient Record System (CPRS) supplying the patient data, so it can be integrated into a variety of electronic medical record systems.