American Heart Association (AHA) 2011 Scientific Sessions : Page 2 of 2

December 12, 2011

High-Dose Statins May Reverse Arterial Plaque and Cut Cardiovascular Risk

New data suggest the maximum doses of rosuvastatin or atorvastatin can treat coronary artery disease (CAD) more effectively than lower doses without compromising patient safety, reported the lead researcher for SATURN (Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin) at the recent AHA meeting. At a press conference, Stephen J. Nicholls, MD, PhD, cardiovascular director, Ohio Cleveland Clinic Coordinating Center for Clinical Research, noted that although the head-to-head comparison of these widely prescribed statins revealed only modest differences between the therapies, both treatments produced a “striking degree of regression.” In an online interview available at the event Website (, Nicholls said SATURN also documented nearly 50% fewer cardiovascular events than other statin trials. “We have a very low event rate in association with [disease] regression—I think that seals the deal,” he said.

SATURN investigators recruited 1385 patients with CAD from 215 centers throughout North and South America, Europe, and Australia and randomized them 1:1 to receive 40 mg of rosuvastatin or
80 mg of atorvastatin daily for 24 months. The majority of patients were men, and the average age was 57 years; clinical and patient characteristics were well balanced between the treatment arms. Participants underwent intravascular ultrasonography (IVUS) at the start and conclusion of the study to assess the volume of atheroma (plaque) in the walls of their coronary
arteries, which was SATURN’s primary end point.

Approximately 25% of patients were lost to follow-up, leaving 1039 for the efficacy analysis. Atheroma volume declined 0.99% in the atorvastatin group versus 1.22% in the rosuvastatin group (P=.017). Although the difference was not statistically significant, “Both treatments produced marked disease regression,” said Nicholls at the press briefing. A second analysis of the IVUS images associated atorvastatin with a 4.4 mm3 reduction in total atheroma volume compared with a 6.4 mm3 reduction for rosuvastatin, which was significant (P=.01). Nicholls said the level of plaque regression, which he called “the holy grail of heart disease treatment,” far exceeded levels observed in previous clinical trials. Nearly two-thirds of participants experienced a decrease in total atheroma volume (65% in the atorvastatin group vs 71% in the rosuvastatin group). The median low-density lipoprotein cholesterol level was slightly lower in the rosuvastatin group than in the atorvastatin arm (62.6 mg/dL vs 70 mg/dL), whereas the average high-density lipoprotein level was slightly higher (50.4 mg/dL vs 48.6 mg/dL).

Despite the high-doses, no new safety concerns with either drug emerged. The atorvastatin group had a significantly greater incidence of alanine transaminase elevation, whereas the rosuvastatin group had significantly higher rates of proteinuria and creatinine kinase elevation; no cases of rhabdomyolysis were observed. Nicholls said the recent concern about a possible link between statin use and diabetes prompted investigators to check glycated hemoglobin levels, but they saw little change.

Summarizing the clinical significance of these findings in the online interview, Nicholls said, “The implications are the drugs are safe at these doses and there’s really a great benefit. We can remove the plaque, and we know that will translate to a reduction in clinical events.” Data from the SATURN study were simultaneously published in the New England Journal of Medicine.—Christin Melton


This study was funded by AstraZeneca.