Impact of statin therapy on coronary artery calcification volume and density – A meta-analysis of randomized controlled trials

Statin therapy leads to not only reduction of cholesterol levels but also stabilization of coronary plaques.(1) In addition, when achieving treatment targets of <70mg/dl, statin therapy has the ability to reduce plaque burden, as documented in randomized controlled trials using intravascular ultrasound (IVUS) of the coronary arteries.(1,2) Coronary artery calcium (CAC)-scoring is a surrogate marker of coronary atherosclerosis and strongly associated with risk for coronary and cardiovascular events.(3-5) The Agatston-Score, combining calcium volume and density, is the most commonly used measure of CAC in clinical routine. However, randomized controlled trials failed to detect a meaningful influence of high intensity statin therapy on the progression of the Agatston-Score in primary prevention cohorts.(6-9) In contrast, recent data from a population based cohort study described an increase in Agatston-Score for subjects under statin medication, suggesting that the stabilizing effect of statins might be reflected in an increase in Agatston-Score, which was confirmed on IVUS-data.(10,11) In addition to the Agatston-Score, the volume and density as alternatively available measure of CAC, have gained interest. Investigators from the Multi-Ethnic Study of atherosclerosis described that CAC-density was inversely related with cardiovascular disease risk.(12) While in a small randomized controlled trial on 66 patients, statin therapy was associated with progression of CAC volume,(13) larger studies on how statin therapy impacts CAC density and volume currently are lacking.

We aim to perform a meta-analysis of two large randomized controlled trials on the association of statin therapy with CAC-progression to determine, whether high-intensity statin therapy leads to a relevant change in CAC volume and density as compared to the traditional Agatston-Score.