Statins effectively reduce cardiovascular disease (CVD) morbidity and mortality. However, even after low-density lipoprotein
cholesterol goal attainment there is a residual CVD risk. To reduce this risk, combining statins with drugs acting on the renin-angiotensin
system (RAS) was investigated. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE), Japanese Coronary Artery
Disease (JCAD), Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) and The Assessing the Treatment Effect in Metabolic Syndrome
Without Perceptible Diabetes (ATTEMPT) trials suggest that the statin plus RAS inhibition combination reduces CVD events
more than a statin alone and considerably more than RAS inhibition alone. This benefit seems to be related to effects on endothelial function,
vascular inflammation and the initiation, progression and rupture of atheromatous plaques. These effects are, at least in part, driven
by mediators, the microRNAs (miRs), that are implicated in the pathogenesis and clinical manifestations of atherosclerosis (e.g. restoration
of endothelial function and attenuation of vascular inflammation). Some miRs are favourably affected by statins and others by RAS
inhibition. There is a miR family (miR-146a/b), related to coronary artery plaque destabilization that is beneficially affected by both statins
and RAS inhibition.
Statins and RAS inhibition combination should be routinely prescribed in high risk patients with CVD, hypertension, obesity, metabolic
syndrome, and/or diabetes to maximize clinical benefit.