Repurposing drugs to treat cardiovascular disease in the era of precision medicine

Abstract

Drug repurposing is the use of a given therapeutic agent for indications other than that for which it was originally designed or intended. The concept is appealing because of potentially lower development costs and shorter timelines than are needed to produce a new drug. To date, drug repurposing for cardiovascular indications has been opportunistic and driven by knowledge of disease mechanisms or serendipitous observation rather than by systematic endeavours to match an existing drug to a new indication. Innovations in two areas of personalized medicine — computational approaches to associate drug effects with disease signatures and predictive model systems to screen drugs for disease-modifying activities — support efforts that together create an efficient pipeline to systematically repurpose drugs to treat cardiovascular disease. Furthermore, new experimental strategies that guide the medicinal chemistry re-engineering of drugs could improve repurposing efforts by tailoring a medicine to its new indication. In this Review, we summarize the historical approach to repurposing and discuss the technological advances that have created a new landscape of opportunities.

The sirtuin family in health and disease

“… 488 CVDs are the major cause of mortality worldwide. 489 , 490 According to the Global Burden of Disease Study 2019, prevalent cases of total CVDs have increased from 271 million to 523 million in 204 countries and territories between 1990 and 2019. The number of CVD deaths has also increased from 12.1 million to 18.6 million.…”

Microfluidics for diagnosis and treatment of cardiovascular disease

“…One is to accurately diagnose diseases through multiple data, and to match heterogeneous diseases with precision medicines. 87,88 The other is to deliver precise drugs to improve the efficiency of drugs acting on targets and reduce the side effects of treatment. 89 The study of drug carriers and the design of multi-targeted drugs are important ways to improve drug efficacy and pharmacokinetics.…”

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

“…Although a "productivity crisis" has been declared across the drug development landscape (Pammolli et al, 2011), this trend does not carry across to other fields such as oncology where approvals have instead increased from 16% to 27% of total approvals over the same period (Zannad et al, 2021). One proposed explanation for this is the difficulty of conducting cardiovascular clinical trials (Fordyce et al, 2015;Zannad et al, 2021;Abdelsayed et al, 2022). Generally, trial regulators require "hard" endpoints like cardiovascular events including MI and stroke, rather than biomarker or surrogate outcomes such as levels of low density lipoprotein or C-reactive protein.…”

“…statins or ACE inhibitors, large patient cohorts and long follow-up periods are needed in order to achieve statistical power in such trials. Together, this makes cardiovascular trials both difficult and, more pertinently, expensive to run (Fordyce et al, 2015;Zannad et al, 2021;Abdelsayed et al, 2022). Drug repurposing and its aforementioned financial advantages could therefore be a particularly useful approach in cardiovascular medicine.…”