Comparison of the Progression of Coronary Atherosclerosis for Two High Efficacy Statin Regimens with Different HDL Effects: SATURN Study Results

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Comparison of the Progression of Coronary
Atherosclerosis for Two High Efficacy Statin
Regimens with Different HDL Effects SATURN Study
Results

• SJ Nicholls, CM Ballantyne, PJ Barter, MJ
  Chapman,
• RM Erbel, P Libby, JS Raichlen, M Borgman,
• K Wolski and SE Nissen

Cleveland Clinic Heart Vascular Institute
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Disclosures

• Research support AstraZeneca, Anthera, Eli
  Lilly, Novartis, Resverlogix, Roche and
  LipoScience
• Consulting and honoraria AstraZeneca, Eli Lilly,
  Anthera, Omthera, Merck, Takeda, Resverlogix,
  Sanofi-Aventis, CSL Behring, Esperion, Boehringer
  Ingelheim
• SATURN was sponsored by AstraZeneca

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Steering Committee

• Steven Nissen (Chair)
• Stephen Nicholls (Principal Investigator)
• Philip Barter
• Christie Ballantyne
• John Chapman
• Raimund Erbel
• Peter Libby
• Joel Raichlen (non-voting)

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Background

• Statins have consistently reduced cardiovascular
  event rates in large randomized controlled
  clinical trials.
• Imaging studies have shown that statins have a
  favorable effect on disease progression.
• The effects on plaque burden appear to
  correlatewith both lowering of LDL-C and raising
  of HDL-C.
• However, no study has compared the effectsof
  maximal dosages of the most efficacious statin
  regimens on progression of coronary
  atherosclerosis.

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Objective

• To compare the effects of rosuvastatin 40 mg
  versus atorvastatin 80 mg on progressionof
  coronary atherosclerosis assessed by
  intravascular ultrasound.

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Study Design
1385 patients with symptomatic CAD (angiographic
stenosis gt20) LDL-C with (gt80 mg/dL) or without
(gt100 mg/dL) statin use last 4 weeks
Rosuvastatin 40 mg (n 694)
Atorva 40 mg
Atorvastatin 80 mg (n691)
Rosuva 20 mg
Visit Week
1 4
3 0
4 13
5 26
6 39
7 52
8 65
9 78
10 91
11 104
2 2
Safety
IVUS Lipids
Lipids
Safety
Safety
LipidsSafety
IVUS Lipids Safety
LipidsSafety
Safety
Safety
LipidsSafety
Randomization Period
Screening Period
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SATURN Trial Flow of Patients
4255 patients screened and 1578 patients treated
at centers in North America, Europe, South
America and Australia
Treatment for 2 weeks with atorvastatin 40 mg or
rosuvastatin 20 mg for 2 weeks to achieve LDL-C
lt116 mg/dL
24 monthstreatment
Atorvastatin 80 mg (n691)
Rosuvastatin 40 mg (n694)

346 (25) patients withdrew or did not have an
evaluable final IVUS
Follow-up IVUS of originally imaged target
vessel (n1039)
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Clinical Characteristics
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Time-Weighted Lipid Levels and hsCRP
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Primary IVUS Efficacy Parameter
Median Change Percent Atheroma Volume
P0.17
-0.99
-1.22
Plt0.001
Plt0.001
comparison between groups. comparison from
baseline
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Secondary IVUS Efficacy Parameter
Median Change in Total Atheroma Volume
Change Total Atheroma Volume (mm3)
P0.01
-4.4
P0.01
-6.4
Plt0.001
comparison between groups. comparison from
baseline
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Fraction of Patients Exhibiting Regression
71.3
68.5
63.2
64.7
Percent of Patients
P0.02
P0.07
Percent Atheroma Volume
Total AtheromaVolume
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Subgroups Demonstrating Heterogeneity
Baseline LDL-C Mean
Baseline HDL-C Mean
Achieved HDL-C Mean
Females
-0.63
-0.61
-0.71
-1.00
-1.44
-1.41
-1.47
P0.01
-1.76
P0.02
P0.02
P0.03
Atorvastatin
Rosuvastatin
P values for heterogeneity
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LDL-C and Disease Progression
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Adverse Events Safety Population (n1385)
P0.04 and P0.02 for comparison between
groups
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Conclusions

• Rosuvastatin 40 mg resulted in moderately lower
  LDL-C and higher HDL-C than atorvastatin 80 mg.
• For the primary IVUS endpoint, the extent of
  regression was similar for both regimens
  (P0.17).
• However, for the secondary IVUS endpoint, a
  greater degree of regression was observed with
  rosuvastatin compared with atorvastatin (P0.01).
• A low number of clinical and biochemical adverse
  events were observed in both groups.

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Publication Available On-line
www.nejm.org
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A Final Thought

• Maximal statin therapy, achieving optimal LDL-C
  and HDL-C levels, is well tolerated and promotes
  extensive disease regression.
• The extent and frequency of regression observed
  in the SATURN trial is unprecedented.
• The finding that nearly one third of patients
  continue to progress supports the need to develop
  additional anti-atherosclerotic therapies.