Original Analysis to determine the Mechanism of Action of ACE Inhibitors in cardiovascular disease

Investigation of the mechanism of action of the cardioprotective effect of ACE inhibitors was carried out. Two clinical trials were analysed in a novel manner. One randomised control trial carried out in Adelaide was the administration of ACE inhibitors for 3 months with the measurement of key biochemical markers. Also baseline patient features were recorded from the history, examination and investigations of patiens. We initially did baseline multiple linear regression models modelling the biochemical markers with other features from patient history etc.  so for a given patient we could predict the value of the biomarker without actually doing the investigation. I then did repeated measures analysis to see if ACE inhibitors had an effect on the biochemical markers.

The second trial was the large SOLVD dataset (13000 observations) which had many of the variables at baseline as did the Adelaide trial. I developed baseline prediction models containing variables common to both trials. I used these models to predict the value of these markers in the larger trial where they were not measured. The values were based on patient history etc.. I then used this value in a recurrent event model looking at cardiovascular hospital readmission. I found that the biomarkers were clinically significant in predicting cardiovascular hospitalisation and that ACE inhibitors worked more effectively in certain quartiles of these markers, thus further elucidating the mechanism of action. For example ACE inihbitors worked more effectively when patiens were in the top quartile of some marker. They were likely to be more effective in the top quartie as that markers was cardiovascularly damaging and ACEi were probably reducing these markers through out the treatment period. 

This has been displayed in the Asia Pacific Chronic Heart Failure Conference APCHF Jan 2008.

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