PhD ceremony Mr. P.A. Smink: Biomarkers and assessment of drug efficacy in cardiovascular disease

PhD ceremony: Mr. P.A. Smink, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Biomarkers and assessment of drug efficacy in cardiovascular disease

Promotor(s): prof. D. de Zeeuw

Faculty: Medical Sciences

In recent years, a number of large clinical drug trials which aimed to investigated whether a novel drug reduces the burden of renal and cardiovascular complications, reported no benefit and sometimes even harm. These results were unexpected since these drugs had shown to have favourable effects on a cardiovascular risk factor, such as blood pressure, cholesterol or Hba1c, so-called on-target risk factors. The explanation may be that drugs exert effects on multiple risk factors, so called off-target effects, which may beneficially or adversely affect the long-term outcome. Thus, to predict the drug effect on long-term outcome, not only the on-target but also the off-target effects should be considered and measured. In my thesis I showed that a blood pressure lowering drug influences multiple risk factors besides blood pressure. Interestingly, the changes in each of these risk factors influence long-term renal or cardiovascular outcome in opposing directions. I showed that a so called Parameter Response Efficacy (PRE) score integrating the drug effect on multiple risk factors performs significantly better in predicting drug effects on renal or cardiovascular outcome than any score based on single on-target or off-target effects. The implications of these results could be that an integrated drug response score can help the regulator to make well-informed decisions on drug efficacy (in the absence of long-term efficacy/safety data) as well as it may help the physician and patient to estimate the long-term drug effect on renal and cardiovascular outcome.