Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin - SATURN

Description:

The goal of the trial was to evaluate treatment with rosuvastatin compared with atorvastatin among patients with symptomatic coronary artery disease.

Hypothesis:

Rosuvastatin will more effective at regressing coronary plaque.

Study Design

  • Blinded
  • Randomized
  • Parallel

Patient Populations:

  • Patients 18-75 years of age with symptomatic coronary artery disease (>20% stenosis) and LDL-C >80 mg/dl on statin therapy, or >100 mg/dl not on statin therapy

    Number of screened applicants: 4,255
    Number of enrollees: 1,039
    Duration of follow-up: 2 years
    Mean patient age: 57 years
    Percentage female: 27%

Exclusions:

  • Intensive statin therapy for >3 months
  • Uncontrolled hypertension
  • Heart failure
  • Renal dysfunction
  • Liver disease

Primary Endpoints:

  • Median change in percent atheroma volume

Secondary Endpoints:

  • Median change in total atheroma volume
  • Major cardiovascular events
  • ALT >3x upper limit of normal
  • Proteinuria

Drug/Procedures Used:

There was an initial run-in period to assess for side effects and compliance where symptomatic patients with coronary artery disease were randomized to rosuvastatin 20 mg versus atorvastatin 40 mg.

After 2 weeks, patients with a low-density lipoprotein cholesterol (LDL-C) <116 mg/dl were randomized again to rosuvastatin 40 mg daily (n = 520) versus atorvastatin 80 mg daily (n = 519). Study drugs were administered for 2 years. Patients had an intravascular ultrasound (IVUS) at baseline and again at follow-up.

Concomitant Medications:

The use of antiplatelet therapy was 98%, beta-blockers 61%, angiotensin-converting enzyme inhibitors 44%, and angiotensin receptor antagonists 17%.

Principal Findings:

Overall, 1,039 patients were randomized and received both baseline and follow-up IVUS. The mean age was 57 years, 27% were women, median body mass index was 29 kg/m2, 14% had diabetes, and 58% had prior statin use.

The mean on-treatment LDL-C level was 63 mg/dl in the rosuvastatin group versus 70 mg/dl in the atorvastatin group (p < 0.001). Mean on-treatment high-density lipoprotein cholesterol (HDL-C) level: 50 mg/dl versus 49 mg/dl (p = 0.01), respectively.

The primary outcome, median change in atheroma volume, was -1.22% in the rosuvastatin group versus -0.99% in the atorvastatin group (p = 0.17). The following subgroups appeared to demonstrate a greater change in percent atheroma volume with rosuvastatin versus atorvastatin: women, baseline LDL-C ≥ mean, baseline HDL-C ≥ mean, and achieved HDL-C ≥ mean.

The secondary outcome, median change in total atheroma volume, was -6.4 mm3 in the rosuvastatin group versus -4.4 mm3 in the atorvastatin group (p = 0.01).

The proportion of patients who had plaque regression, as measured by percent atheroma volume, was 69% versus 63% (p = 0.07), and as measured by total atheroma volume was 71% versus 65% (p = 0.02), respectively.

Major adverse cardiovascular event: 7.5% versus 7.1%, alanine aminotransferase (ALT) >3x upper limit of normal: 0.7% versus 2.1% (p = 0.04), and proteinuria: 3.8% versus 1.7% (p = 0.02), respectively.

Interpretation:

Among patients with symptomatic coronary artery disease, rosuvastatin resulted in a modest reduction in LDL-C (∆ 7 mg/dl) and a very modest increase in HDL-C (∆ 1 mg/dl) versus atorvastatin. Change in percent atheroma volume (primary outcome) was similar between the two groups; however, rosuvastatin was associated with a larger reduction in total atheroma volume (secondary outcome).

Major cardiovascular events were similar between the groups; however, rosuvastatin was associated with less frequent elevation in ALT, but more frequent proteinuria. The clinical difference between these two intensive statin medications may be marginal since they demonstrated similar ability to regress atherosclerosis.

References:

Nicholls SJ, Ballantyne CM, Barter PJ, et al. Effect of Two Intensive Statin Regimens on Progression of Coronary Disease. N Engl J Med 2011;Nov 15:[Epub ahead of print].

Presented by Dr. Stephen Nicholls at the American Heart Association Scientific Sessions, Orlando, FL, November 15, 2011.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Lipid Metabolism, Nonstatins, Statins

Keywords: Fluorobenzenes, Coronary Artery Disease, Follow-Up Studies, Atherosclerosis, Plaque, Atherosclerotic, Cholesterol, LDL, Pyrimidines, Proteinuria, Heptanoic Acids, Lipoproteins, LDL, Pyrroles, Body Mass Index, Cholesterol, HDL, Lipoproteins, HDL, Diabetes Mellitus, Sulfonamides


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