In light of the data from SATURN and the impending arrival of generic atorvastatin, what is the appropriate role of rosuvastatin at this point?
Steven E. Nissen, MD (senior author of SATURN)
The SATURN Trial demonstrated statistically significant regression of coronary disease in patients treated with the maximum approved dosages of the two most efficacious statins (atorvastatin and rosuvastatin) administered at their highest approved dosages. Despite moderate differences in LDL and HDL favoring rosuvastatin, for the primary efficacy measure, the extent of regression did not differ between treatment groups.
These findings suggest that most patients can be optimally treated with atorvastatin when it becomes generic, which may offer excellent benefits at a lower cost.
Although a small difference in efficacy was observed for the secondary intravascular ultrasound endpoint, this finding should be interpreted with caution. It must also be acknowledged that SATURN was an imaging trial, not a morbidity/mortality trial. We need more comparative effectiveness trials with clinical endpoints to optimally chose the most effective therapies. The excellent safety observed in SATURN suggests that most patients can be readily treated with maximal dosage of these two statins.
SATURN suggests that in patients with CAD and LDL levels treated to below current clinical guidelines, atorvastatin and rosuvastatin are equivalent in terms of regression. In light of atrovostatin’s (soon to be) generic formulation, and its efficacy, potency, and known clinical outcomes in a wide range of patients across both primary and secondary prevention, it seems that rosuvastatin should be reserved for patients intolerant to high-dose atorvastatin, patients unable to achieve clinical guidelines for LDL reduction, or patients in whom clinical trials such as JUPITER inform use.
Atorvastatin will continue to be the dominant statin since it can be used with calcium channel blockers and it is nearly as potent as rosuvastatin. Perhaps a longer follow-up than 104 weeks would have shown a modest benefit for rosuvastatin, but we will never know. The cost of atorvastatin will be much less in 2012. Of note, the HDL-C levels on rosuvastatin were not much higher than on atorvastatin therapy. There is a signal that rosuvastatin may promote more regression than atorvastatin but the clinical significance is unclear.
The limitations of using intravascular ultrasound to assess regression of atherosclerosis were also discussed in the editorial about ASTEROID that Navin Kapur and I co-wrote in JAMA in April 2006. It is interesting that the REVERSAL trial did not find any regression with atorvastatin, but SATURN does. Nevertheless, the pioneering work of Drs. Nissen and Nichols has revolutionized the current approach to understanding the pathophysiology of coronary atherosclerosis as well as its responsiveness to therapy. I think that rosuvastatin will be used more than atorvastatin when the starting HDL-C is low or when there is concern about drug interactions.