Drug repurposing in cardiovascular inflammation: Successes, failures, and future opportunities

Drug repurposing is an attractive, pragmatic approach to drug discovery that has yielded success across medical fields over the years. The use of existing medicines for novel indications enables dramatically reduced development costs and timescales compared with de novo drug discovery and is therefore a promising strategy in cardiovascular disease, where new drug approvals lag significantly behind that of other fields. Extensive evidence from pre-clinical and clinical studies show that chronic inflammation is a driver of pathology in cardiovascular disease, and many efforts have been made to target cardiovascular inflammation therapeutically. This approach has been met with significant challenges however, namely off-target effects associated with broad-spectrum immunosuppression, particularly in long-term conditions such as cardiovascular disease. Nevertheless, multiple anti-inflammatory medicines have been assessed for efficacy in cardiovascular clinical trials, with most of these being repurposed from their original indications in autoimmune conditions like rheumatoid arthritis. In this review, we discuss the mixed successes of clinical trials investigating anti-inflammatory drugs in cardiovascular disease, with examples such as anti-cytokine monoclonal antibodies, colchicine, and methotrexate. Looking to the future, we highlight potential new directions for drug repurposing in cardiovascular inflammation, including the emerging concepts of drug re-engineering and chrono-pharmacology.