Cardiovascular clinical trials are increasingly costly and, in the current era of highly effective risk modifying therapies, the plausible benefits of new compounds are modest and the need for more efficient trial designs is rising. We will conduct observational and genetic studies to elucidate the effects of established and novel cardiovascular drug targets to inform trial design and therapeutic indications. Examining observational associations can identify patient groups most likely to benefit or at risk of side-effects and examining genetic variants that mimic the biological drug target can help anticipate treatment effects, facilitating better trial designs and use of treatment. Numerous medications have been proven to be highly effective at reducing cardiovascular events in randomised trials and are now considered standard therapy for high-risk patients (e.g. statins, aspirin, blood-pressure lowering medications). However, despite improvements in our understanding and ability to manage cardiovascular risk factors, cardiovascular disease remains a leading cause of morbidity and mortality worldwide and additional therapies are needed. The proposed research will enhance our understanding of cardiovascular drug targets, improve appropriate therapeutic usage of cardiovascular drugs, facilitate improved efficiency and design of clinical trials, and promote the emergence of effective novel therapies for cardiovascular disease. The research plan will investigate:
– The associations of observational and biochemical measures on side-effects of cardiovascular therapies in relation to the expected benefit, such as bleeding and aspirin use.
– Influence of genetic variants on therapeutic targets, such as a Lp(a), and with risk factors and side-effects of cardiovascular therapies.
– Associations between genetic variants that mimic drug targets and characteristics, biomarkers, and disease in order to identify subgroup, pleiotropic and side-effects of treatment.
– Differences in the effects of drug targets by genetic and non-genetic factors.
– The methodological impact on clinical trial design and treatment use.
Full cohort