Atorvastatin has an important acute anti-inflammatory effect in patients with acute coronary syndrome: Results of a randomized, double-blind, placebo-controlled study Stella M. Macin, MD, a Eduardo R. Perna, MD, a Eduardo F. Farı ´as, MD, a Valeria Franciosi, MD, a Jorge R. Cialzeta, MD, a Mo ´ nica Brizuela, BSc, b Fernanda Medina, BSc, b Carlos Tajer, MD, c Hernan Doval, MD, c and Reynaldo Badaracco, MD a Corrientes and Buenos Aires, Argentina Background C-reactive protein (CRP) levels are associated with cardiovascular risk. We assessed the hypothesis that atorvastatin might have anti-inflammatory effects in acute coronary syndromes (ACS) as shown by CRP reduction. Methods This study was a prospective, randomized, double-blind, placebo-controlled study of 90 consecutive patients admitted within 48 hours of onset of ACS with CRP levels z1.4 mg/dL. Patients were assigned to atorvastatin 40 mg daily or placebo over 30 days. C-reactive protein levels, lipid profiles, serum fibrinogen, white cell count, and erythrocyte sedimentation rate were measured at entry, hospital discharge, and 1 month later. Results Baseline clinical characteristics did not differ between atorvastatin and placebo groups (mean age 59.3 F 13.4 vs 61.1 F 11.5, P = ns); myocardial infarction 52.3% versus 67.4% ( P = ns). In both groups, median baseline CRP levels were comparable (5.97 F 6.2 vs 4.64 F 4.2 mg/dL, P = ns). C-reactive protein levels were lower in the atorvastatin group versus control group at discharge (1.68 F 1.65 vs 4.12 F 4.18 mg/dL) and at 30 days (0.50 F 0.71 vs 2.91 F 2.68 mg/dL, both P b .0001). C-reactive protein levels significantly decreased from baseline to discharge and 1 month later in placebo and atorvastatin groups (both P b .0001); however, the reduction was greater in the atorvastatin group (62% vs 11% at discharge [ P b .0001]; 84% vs 30% at 1 month [ P b .0001]). In addition, atorvastatin was associated with a reduction in total and low-density lipoprotein cholesterol and erythrocyte sedimentation rate at discharge and at 30 days ( P b .0001 for all comparisons). No correlation was found between changes in CRP and cholesterol levels. Conclusions C-reactive protein levels in ACS were rapidly reduced with atorvastatin. These data provide evidence that statins have fast and early anti-inflammatory effects in addition to lipid-lowering effects in ACS. (Am Heart J 2005;149:451- 7.) See related Editorial on page 377. Atherosclerosis is considered an inflammatory dis- ease. 1,2 C-reactive protein (CRP) is associated with cardiovascular risk, 3-6 and several studies have demon- strated that statins decrease CRP levels in primary as well as secondary prevention. 7-12 Recently, the MIRACL trial has demonstrated that the early use of high dose of atorvastatin (80 mg/d) started within 24 to 96 hours of admission for angina or non–Q-wave myocardial in- farction (MI) reduced recurrent ischemic events over a 16-week treatment period and decreased inflammatory markers compared with placebo after 16 weeks of treatment. 13 Atorvastatin was associated with an 83% reduction in CRP levels compared with 74% in the placebo group. 14 However, the effect of statins on acute inflammatory response during hospitalization has been poorly evaluated. We assessed the hypothesis that atorvastatin might have early anti-inflammatory effects in acute coronary syndromes (ACS). Thus, the primary objective of this study was to evaluate the effect of atorvastatin admin- istered early after admission in patients with ACS on CRP levels measured at discharge and at 30 days. Methods Study population This study was a prospective, randomized, double-blind, placebo-controlled trial carried out in a single institution From the a Coronary Intensive Care Unit, b Laboratory, Instituto de Cardiologı ´a bJuana F. Cabral,Q Corrientes, Argentina, and c GEDIC Group, Buenos Aires, Argentina. Submitted June 15, 2004; accepted July 27, 2004. Reprint requests: Stella M. Macı ´n, MD, Coronary Intensive Care Unit, Instituto de Cardiologı ´a bJuana F. Cabral,Q Bolı ´var 1334, Corrientes, 3400, Argentina. E-mail: macinucic@hotmail.com 0002-8703/$ - see front matter n 2005, Elsevier Inc. All rights reserved. doi:10.1016/j.ahj.2004.07.041