Improving treatment efficacy in hypertension by biomarker-guided personalised decision support

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In HT-ADVANCE we aim to revolutionise personalised management of arterial hypertension (HT) by using multi-omics (MOMICS) stratification biomarkers as companion diagnostics for the prescription of existing drugs. HT is the most important global risk factor for death and morbidity but is uncontrolled in more than 50% of patients. Causes of treatment failure include lack of identification of secondary forms such as endocrine hypertension (EHT) which can be curable by specific therapy. In addition, there is variable response to individual drugs and trial-and-error treatment leads to poor HT control and frustration for both patients and clinicians. The objective of HT-ADVANCE is to validate two multicomponent stratification biomarkers in patients with HT in order to i) identify patients with EHT, and ii) predict response to treatment in patients with primary hypertension. The hypothesis is that MOMICS biomarkers reflect specific forms of hypertension and susceptibility to specific drugs. To this end, we will run three clinical trials (HT-ENDO, HT-TREAT and HT-PREDICT) and apply machine learning techniques to integrate the genetic, genomic and metabolomic features that constitute the MOMICS biomarkers in order to generate accurate diagnostic and therapeutic response predictions for clinicians. We will also perform economic evaluation of the use of MOMICS for the treatment of HT, produce ethical and legal recommendations for clinical decision making, and develop a plan for their implementation as companion diagnostics. The study will be conducted by several HT Centres of Excellence and will build on the success of the ENSAT-HT project that has established methods and pipelines for integrating datasets derived from multiple platforms. We expect that HT-ADVANCE will provide a step change in the management of HT by enabling a personalised, more efficient and cost-effective treatment strategy, and importantly, will prevent the ensuing cardio-metabolic complications.