Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin versus Atorvastatin (SATURN) study

The Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin versus Atorvastatin (SATURN) study compared treatment with two high-dose statins (atorvastatin 80 mg daily or rosuvastatin 40 mg daily).

• in the SATURN study, after a run-in period of two weeks, 1,385 patients with coronary heart disease were randomly assigned to high-intensity treatment with atorvastatin 80 mg daily or rosuvastatin 40 mg daily
  • the primary efficacy end point, percent atheroma volume (PAV) (measured by intravascular ultrasound)
  • after two years of treatment, there was no statistically significant difference between atorvastatin and rosuvastatin in the primary outcome: atheroma volume decreased by 0.99% (95% confidence interval [CI] -1.19 to -0.63) from baseline with atorvastatin and 1.22% (95% CI, -1.52 to -0.90) with rosuvastatin (p for change from baseline for each <0.001; p for between-group comparison 0.17)
  • both atorvastatin and rosuvastatin resulted in regression of atherosclerosis in the majority of patients (63.2% with atorvastatin and 68.5% with rosuvastatin, based on change in percent atheroma value), with no statistically significant difference between the two treatments (p = 0.07)
  • the study authors concluded that "...maximal doses of rosuvastatin and atorvastatin resulted in significant regression of coronary atherosclerosis. Despite the lower level of LDL cholesterol and the higher level of HDL cholesterol achieved with rosuvastatin, a similar degree of regression of PAV was observed in the two treatment groups.."(1)
    
• both groups saw a regression of coronary atherosclerosis from baseline in around two thirds of patients with coronary heart disease, but there was no statistically significant difference between the two groups. Reduction in atherosclerotic plaque volume is a surrogate or disease-oriented outcome and it is unclear how this translates into patient-oriented outcomes such as reduction in risk of cardiovascular(CV) events. Other limitations in the study further reduce its application to direct patient care (2)

Comparing use of statins versus statins plus high intensity interval training (HIIT) in achieving plaque regression

• in the Cenit study, 60 patients with a history of coronary artery disease (CAD) were randomised to either HIIT (x2 supervised sessions per week) versus lifestyle advice in addition to usual lipid lowering and antiplatelet therapy
• the intervention was for 6 months
• observed that, at 6 months, total atheroma volume (TAV) was significantly reduced by 9.0 mm3 after HIIT, while it tended to increase in the control group percent atheroma volume (PAV) was reduced by 1.2% in the HIIT group but not in the control group
• study authors concluded that:
  • patients with established CAD, a regression of atheroma volume was observed in those undergoing 6 months of supervised HIIT compared with patients following contemporary preventive guidelines

A meta-analysis has shown that each 1% reduction in PAV was associated with a 20% reduction in the odds of major adverse cardiovascular events (4).

Reference:

• 1) Nicholls SJ, Ballantyne CM, Barber PJ, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011:365:2078-87
• 2) MeReC Extra No. 52(February 2012)
• 3) Vesterbekkmo EK et al. High-intensity interval training induces beneficial effects on coronary atheromatous plaques: a randomized trial. Eur J Prev Cardiol. 2023 Mar 27;30(5):384-392. doi: 10.1093/eurjpc/zwac309. PMID: 36562212. (https://pubmed.ncbi.nlm.nih.gov/36562212/)
• 4) Ference BA et al Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017 Aug 21;38(32):2459-2472