American Heart Association Scientific Sessions 2011

SATURN: Discussion

• • • Design, conduct and analysis Outcomes Interpretation

Darwin R. Labarthe, MD, MPH, PhD Professor of Preventive Medicine Northwestern University Feinberg School of Medicine No conflicts to disclose

SATURN

Design, conduct and analysis

Question: Is there a significant difference in percent change in atheroma volume as determined by intravascular ultrasonography (IVUS) at baseline and 79-104 weeks later, between 2 groups of patients, each with 20+% stenosis in at least 1 coronary artery at entry?

Intervention: Random allocation to receive either atorvastatin (A) (80mg/d) or rosuvastatin (R) (40 mg/d) for 24 months.

Population: 4255 patients screened  1385 randomized  Australia (~5 patients/center).

 1578 treated in pretrial phase 1039 analyzed: predominantly male, `57 yo, overweight, largely hypertensive (~70%), partly diabetic (~15%), multiple other medications; 215 centers in N/S America, Europe, Conduct: Losses to outcome evaluation = 346 (29%) of 1385 randomized patients, incl. 9 (A), 20(R) lost to follow-up; therefore analysis could not be conducted by “intention to treat”.

SATURN

Outcome

Primary outcome: Change in percent atheroma volume = 0.99% (A) v. -1.22% (R) (difference = 0.23%, P = 0.17, not statistically significant).

Secondary outcome: Change in total atheroma volume = -4.4 mm 3 (A) v. -6.4 mm 3 in (R) (difference = 2.0 mm 3 , P=0.01, statistically significant). Other notable findings: (R) v (A ): lower time-weighted LDL C, slightly higher HDL-C, higher triglycerides and hsCRP; first major cardiovascular adverse cardiovascular events (undefined) = 7.1% (A) v 7.5% (R).

SATURN

Interpretation

a. If the primary outcome reflects the true relation between the two interventions, there is no difference between (A) and (R) in reduction of atheroma – despite lower LDL-C and higher HDL-C with (R) v. (A).

b. If the secondary outcome reflects the true relation between the two interventions, (R) is more effective than (A) in reduction of atheroma.

c. The findings of the study are inconclusive regarding the study question: (1) there is no significant difference regarding the primary outcome among evaluated patients; (2) these results regarding the secondary outcome are inconsistent with (1); and (3) outcomes are unknown for 346 (29%) of the randomized study population from endpoint evaluation – experience of these patients who could not be evaluated could change the findings substantially.

d. Regardless of these findings, the study provides no basis to infer differential clinical benefit between (A) and (R).