Coronary calcium scoring – Not a suitable endpoint for clinical trials

Coronary calification is viewed as the endpoint of the atherosclerotic disease process.  As such, whether it can be used to monitor changes in response to novel and existing pharmaceutical  therapies remains unknown.  To address this question, McCullough and Chinnaiyan performed a meta-analysis of the only ten trials in which coronary artery calcium (CAC) was measured at baseline and then at least one year later.

Five of the trials included patients with cardiovascular disease, while five included patients with chronic renal disease.  Both Agatston and volumetric methods were used to evaluate the amount of CAC, and various pharamaceutical interventions were tested in the ten trials.  The average annual CAC increase was 17.2% overall (16.9% for patients with cardiovascular disease and 18.4% for patients with chronic renal disease, P<0.001).  However, only two trials included in the analysis were placebo controlled and the CAC progression rate in this group was 14.6%.  Of the five studies that had reported outcomes in terms of CAC progression between the treatment and the control arm, no statistically significant difference was seen in any of the studies.  Furthermore, the correlation between LDL-C change and CAC progression was found to be very weak (r=0.10, P<.001).
It should be noted that this is an imperfect meta-analysis; the trials included used slightly different methods to assess CAC changes to several different treatments in different populations.  Nonetheless, it emphasises that, currently, no link has been found been CAC reduction and cardiovascular outcomes.
In this meta-analysis, the 1-year change in CAC did not seem to be a suitable biomarker for assessing the impact of pharmacotherapy on the burden of coronary artery disease.  A variety of ongoing trials continue to examine the role of CAC scoring in monitoring responses to drug therapies.

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