Effect of two intensive statin regimens on progression of coronary diseaseLiterature - 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.
IntroductionStatins 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.
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.
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 . The highest doses (atorvastatin: 80 mg daily; rosuvastatin: 40 mg daily) were compared.
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.
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.
References1. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994;344:1383-9.
2. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998;339:1349-57.
3. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002;360:7-22.
4. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS: AirForce/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279:1615-22.
5. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001-9.
6. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med 1995;333:1301-7.
7. Pedersen TR, Faergeman O, Kastelein JJ, et al. High-dose atorvastatin vs usual dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA 2005;294:2437-45. [Erratum, JAMA 2005;294:3092.]
8. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med 2005;352:1425-35.
9. Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 2008;359:2195-207.
10. 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;376:1670-81.
11. 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;291:1071-80.
12. 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;295:1556-65.
13. Jones PH, Davidson MH, Stein EA, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR Trial). Am J Cardiol 2003;92:152-60.
14. Nicholls SJ, Brandrup-Wognsen G, Palmer M, Barter PJ. Meta-analysis of comparative efficacy of increasing dose of atorvastatin versus rosuvastatin versus simvastatin on lowering levels of atherogenic lipids (from VOYAGER). Am J Cardiol 2010;105:69-76.
15. Barter PJ, Brandrup-Wognsen G, Palmer MK, Nicholls SJ. Effect of statins on HDL-C: a complex process unrelated to changes in LDL-C: analysis of the VOYAGER database. J Lipid Res 2010;51:1546-53.
16. Nicholls SJ, Sipahi I, Schoenhagen P, Crowe T, Tuzcu EM, Nissen SE. Application of intravascular ultrasound in antiatherosclerotic drug development. Nat Rev Drug Discov 2006;5:485-92.