Physicians' Academy for Cardiovascular Education

Effect of two intensive statin regimens on progression of coronary disease

Literature - Nicholls SJ, N Engl J Med. 2011 Dec 1;365(22):2078-87

Effect of two intensive statin regimens on progression of coronary disease


Nicholls SJ, Ballantyne CM, Barter PJ, Chapman MJ, Erbel RM, Libby P, Raichlen JS, Uno K, Borgman M, Wolski K, Nissen SE.
N Engl J Med. 2011 Dec 1;365(22):2078-87. Epub 2011 Nov 15.

Introduction

Statins reduce adverse cardiovascular outcomes and slow the progression of coronary atherosclerosis in proportion to their ability to reduce low-density lipoprotein (LDL) cholesterol. However, few studies have either assessed the ability of intensive statin treatments to achieve disease regression or compared alternative approaches to maximal statin administration.


Methods

We performed serial intravascular ultrasonography in 1039 patients with coronary disease, at baseline and after 104 weeks of treatment with either atorvastatin, 80 mg daily, or rosuvastatin, 40 mg daily, to compare the effect of these two intensive statin regimens on the progression of coronary atherosclerosis, as well as to assess their safety and side-effect profiles.

 

Results

After 104 weeks of therapy, the rosuvastatin group had lower levels of LDL cholesterol than the atorvastatin group (62.6 vs. 70.2 mg per deciliter [1.62 vs. 1.82 mmol per liter], P<0.001), and higher levels of high-density lipoprotein (HDL) cholesterol (50.4 vs. 48.6 mg per deciliter [1.30 vs. 1.26 mmol per liter], P=0.01). The primary efficacy end point, percent atheroma volume (PAV), decreased by 0.99% (95% confidence interval [CI], -1.19 to -0.63) with atorvastatin and by 1.22% (95% CI, -1.52 to -0.90) with rosuvastatin (P=0.17). The effect on the secondary efficacy end point, normalized total atheroma volume (TAV), was more favorable with rosuvastatin than with atorvastatin: -6.39 mm(3) (95% CI, -7.52 to -5.12), as compared with -4.42 mm(3) (95% CI, -5.98 to -3.26) (P=0.01). Both agents induced regression in the majority of patients: 63.2% with atorvastatin and 68.5% with rosuvastatin for PAV (P=0.07) and 64.7% and 71.3%, respectively, for TAV (P=0.02). Both agents had acceptable side-effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events.

ConclusionsMaximal 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.


Background

From many randomized clinical trials it became clear that statins reduce cardiovascular morbidity and mortality across a range of LDL-levels [1-10]. Intensive treatment strategies may slow the progression of coronary atherosclerosis or even regression [11,12].
Atorvastatin and rosuvastatin are most effective in lowering LDL-C levels, with reductions of almost/more than 50%, respectively [13,14]. Although comparative studies showed that rosuvastatin caused greater reductions in LDL-C levels and greater increases in HDL-C levels[13,14,15], the clinical impact of these findings is still unclear.

This study was aimed to directly compare the effects of both agents on disease progression or cardiovascular event rates by using intravascular ultrasonography, by which the effect of treatment on atherosclerotic plaques in the coronary arteries can be measured [16]. The highest doses (atorvastatin: 80 mg daily; rosuvastatin: 40 mg daily) were compared.


Main results

Rosuvastatin 40 mg resulted in slightly lower LDL-C (62.6 vs 70.2 mg/dL / 1.62 vs 1.82 mmol/L, P<0.001) and higher HDL-C (50.4 vs 48.6 mg/dL / 1.30 vs 1.26 mmol/L, P=0.01) than atorvastatin 80 mg. For the primary IVUS endpoint (percent atheroma volume), the extent of regression was similar for both regimens (P=0.17). For the secondary IVUS endpoint (normalized total atheroma volume), a greater degree of regression was observed with rosuvastatin compared with atorvastatin (P=0.01).
In both groups, a low number of clinical and biochemical adverse events were observed.


Conclusion

Maximal doses of both statins is well tolerated and promotes extensive disease regression.
Nevertheless, a considerable amount of patients still shows disease progression; therefore there is a need for new anti-atherosclerotic therapies.
SATURN: Objective
SATURN; Study Design
SATURN Trial: Flow of Patients
SATURN: Clinical Characteristics
SATURN: Time-Weighted Lipid Levels and hsCRP
SATURN: Primary IVUS Efficacy Parameter
LDL-C and Disease Progression

References

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