15289-s-bos

148 | Chapter 9 study (FOURIER) showed a reduction of CVD events when the PCSK9 inhibitor was used on top of high dose statin therapy (8). This new therapy grands new possibilities in lowering LDL-C and subsequently CVD risk reduction. However, the costs of these novel agents are high. In the Unites States the launched list price of Alirocumab and Evolocumab were $14,600 and $14,100 per patient per year respectively (9). Recently Schulman et al. questioned the cost effectiveness of these drugs in hyperlipidaemia patients (9). Since the costs are so high and the absolute CVD risk prevention in these statin treated patients will probably be quite low, the economic benefits seem to be limited. Although, these were: 1) not the formal economic evaluations; 2) the exact reduction in CVD events is currently unknown, and 3) the price will probably be reduced when available in the Netherlands. Given the high costs of these agents it certainly emphasizes the benefit of determining residual risk not only from a health perspective but also in reducing healthcare costs. Cardiovascular imaging In the general population C-IMT and the presence of carotid artery plaques in particular, are significant predictors of CVD (10-13). Because of this association in the general population many studies including drug trials, have used C-IMT as a surrogate marker for atherosclerotic disease to determine the effectiveness of novel agents (14-16). An important factor to considerwhen investigatingandcomparingcarotidultrasonography outcomes in multicentre studies and meta-analysis is the use of different devices, measurement techniques, measurement software and inter-observer variability might yield very different results. I showed in chapter 2 that the outcomes between the devices and different observers used for the studies in this thesis was within acceptable range. One of the landmark trials using C-IMT as endpoint was the ENHANCE trial which randomized FH patients using simvastatin to addition of placebo or ezetimibe. This trial showed that the addition of ezetimibe in these patients did not result in difference in changes in C-IMT between the 2 groups. Later the IMPROVED trial showed that the addition of ezetimibe compared to placebo on top of statin therapy led to a decrease in CVD events. A proposed explanation for the lack of effect of ezetimibe in the ENHANCE trial was that the statin-treated FH patients included in this trial had normalized C-IMT values at baseline. In chapter 3 I showed indeed a normalization in C-IMT values in statin treated FH patients compared to healthy controls. Interestingly plaque presence, measured by ultrasonography, was associated with the severity of coronary atherosclerosis as depicted by CTCA in a subgroup of statin-treated