Benefit-risk assessment of rosuvastatin in the treatment of atherosclerosis and related diseases.

Rosuvastatin has been marketed for approximately a decade. In this review we critically discuss available evidence on the benefits and risks from its use. In clinical trials using rosuvastatin, 'lowest is best' was relevant for on-treatment low-density lipoprotein cholesterol levels. Targeting levels <50 mg/dl was associated with the greatest decrease in vascular morbidity/mortality in the primary prevention setting. Also, such reduction can induce atherosclerosis regression without increasing the risk of adverse effects. Pooled data suggest that the safety profile of rosuvastatin is not different from that of other statins. It was estimated that rosuvastatin-associated absolute hazards of muscle-, liver- and renal-related adverse effects are lower than the corresponding vascular benefits in moderate vascular risk individuals. However, these data are subject to biases and need confirmation on a prospective basis. Significant liver enzyme elevations are rare. These often imply underlying non-alcoholic fatty liver disease (NAFLD), which is associated with increased vascular risk. Rosuvastatin can improve biochemical biomarkers and histological score of NAFLD. Whether this benefit is associated with vascular risk reduction should be assessed by prospective studies. Both chronic kidney disease and albuminuria independently predict vascular morbidity and mortality. Rosuvastatin improved the estimated glomerular filtration rate and decreased albuminuria in patients with moderately impaired kidney function. Also, vascular morbidity and mortality might be reduced in these patients. The same was not relevant in end-stage renal disease. Rosuvastatin-induced proteinuria appears to be of tubular origin, not relating to kidney injury. Rosuvastatin increases the risk of new-onset diabetes by dose-dependently impairing insulin sensitivity. Obese individuals with prediabetes appear to be predominantly affected. However, absolute vascular benefits of rosuvastatin may counterbalance this risk. Rosuvastatin is effective for the prevention and management of atherosclerotic vascular disease. Individualization of its use can maximize benefits and reduce the risk of adverse effects.