Physicians' Academy for Cardiovascular Education

Potent statin therapy affects disease progression in higher-risk patients

Literature - Puri R, Nissen SE, Ballantyne CM, et al. - Eur Heart J. 2013 May 3. [Epub]

Factors underlying regression of coronary atheroma with potent statin therapy.

Puri R, Nissen SE, Ballantyne CM, et al.
Eur Heart J. 2013 May 3. [Epub]
 

Background

High-dose statin regimens improve clinical outcomes in patients at high risk for future cardiovascular events [1 – 4]. Intensive statin therapy can halt the progression of atherosclerosis [5] and even induce disease regression [6] for reasons that are not yet fully understood.
Beyond their ability to lower levels of atherogenic lipoproteins, statins may also exert a direct effect upon the arterial wall [7]. Arterial wall remodeling plays a pivotal role in the clinical expression of atherosclerotic disease.
It is of interest to understand whether factors that influence different measures of progression or regression of coronary atherosclerosis are similar. In the Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) the highest dose of rosuvastatin produced greater regression of total atheroma volume (TAV), but not of per cent atheroma volume (PAV), when compared with high-dose atorvastatin [8]. Serial intravascular ultrasound (IVUS) was used to monitor these changes. The current analysis tried to characterize factors associated with regression of different measures of coronary atherosclerosis in  1039 patients included in SATURN, who were treated with atorvastatin (80 mg) or rosuvastatin (40 mg) daily for 24 months.
 

Main results

  • Reductions in LDL-C were 40.1% and 47.2% for atorvastatin-treated patients and rosuvastatin-treated patients, respectively (P<0.001).
  • HDL-C was increased with 10.0 vs 12.7%, respectively (P=0.02).
  • The atorvastatin-treated group experienced greater per cent reductions in triglyceride levels  (13.2% vs. 26.2%, P = 0.007).
  • C-reactive protein decreased by 25.0% with atorvastatin and 23.7% with rosuvastatin (P= 0.34).
  • TAV regression  was 24.4 vs. 26.4 mm3 for atorvastatin-treated patients and rosuvastatin-treated patients, respectively; P = 0.01; PAV regression was20.99 vs. 21.22 %, respectively; P = 0.17.
  • Both higher baseline TAV and PAV independently associated with TAV and PAV regression, respectively, in a multivariable analysis assessing change in TAV and PAV (standardized estimates: TAV -0.25, P < 0.001; PAV -0.23, P < 0.001)
 

Conclusion

Higher-risk patients, particularly those with greater baseline coronary atheroma volume, are more likely to experience disease regression with potent statin therapy. These findings describe the variable clinical and biochemical characteristics affecting the natural course of coronary atherosclerosis, the arterial wall response, and highlight the need for additional therapeutic targets to tackle the residual burden of disease.
 

References

1. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495–1504.
2. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet 2010;376:1670–1681.
3. Mills EJ, O’Regan C, Eyawo O, et al. Intensive statin therapy compared with moderate dosing for prevention of cardiovascular events: a meta-analysis of .40 000 patients. Eur Heart J 2011;32:1409–1415.
4. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425–1435.
5. Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JAMA 2004;291:1071–1080.
6. Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA 2006;295:1556–1565.
7. Schoenhagen P, Tuzcu EM, Apperson-Hansen C, et al. Determinants of arterial wall remodeling during lipid-lowering therapy: serial intravascular ultrasound observations from the Reversal of atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial. Circulation 2006;113:2826–2834.
8. Nicholls SJ, Ballantyne CM, Barter PJ, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med 2011;365:2078–2087.

 
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