Robert Helm, MD (top) is fellow, Division of Cardiology and Roger S. Blumenthal, MD, is director, Ciccarone Center for the Prevention of Heart Disease, and associate professor of medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland.

Numerous clinical trials have shown that HMG CoA reductase inhibitor (statin) therapy reduces the risk of myocardial infarction (MI), stroke, and mortality in patients with cardiovascular disease. However, the benefit of early statin use in patients with acute MI who have had reperfusion with primary percutaneous coronary intervention (PCI) is less clear. In this issue, Sakamoto and colleagues present results of a multicenter, randomized controlled trial evaluating the effect of early statin therapy on 486 Japanese patients with acute MI treated with primary PCI.¹ In that study, they reported a 4.3% absolute decrease and a 42% relative decrease (7/15 in the statin group vs 26/29 in the nonstatin group) in the composite end point of recurrent symptomatic ischemia and congestive heart failure at 2 years of follow-up. There was no difference in the rate of cardiovascular death, nonfatal acute MI, or nonfatal stroke. In addition, there was no difference in the rate of revascularization procedures, including coronary artery bypass graft surgery or PCI.

Although statin therapy after MI is virtually the standard of care in the United States, this study shows the benefit of early statin treatment in patients with acute MI treated primarily with PCI. Larger randomized controlled trials have shown a similar benefit in patients with acute coronary syndromes (ACS) and non–ST-segment elevation MI. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study showed a significant reduction (6.2% with atorvastatin [Lipitor] vs 8.4% with placebo; relative risk [RR], 0.74) in recurrent ischemic events.² However, the MIRACL study did not show a reduction in new or worsening heart failure (2.8% with atorvastatin vs 2.6% with placebo; RR, 0.94).

Briel and colleagues conducted a meta-analysis of 12 randomized controlled trials that evaluated the early use of statin therapy in ACS.³ Although there was no difference in the rate of unstable angina at 1 month, the rate was reduced to 4.8% in the early statin groups compared with 6.0% in the control groups at 4 months, for an RR reduction of 0.80 (P = .05). The totality of the evidence to date suggests that early, aggressive lipid lowering with statins slows the progression of or may even modestly reduce atherosclerotic plaque burden and decreases the incidence of recurrent symptomatic ischemia.

The study by Sakamoto and colleagues failed to show a reduction in cardiovascular death, nonfatal acute MI, and nonfatal stroke. The sample size, with a relatively small number of events, and the relatively short duration of the study clearly limited the power of the study to show a difference in these end points. Larger randomized controlled trials that included stable patients who had a prior acute MI, such as the Cholesterol and Recurrent Events (CARE) trial, have shown a reduction in these end points.⁴ Over 5 years, the CARE study showed a 24% risk reduction (10.2% with pravastatin [Pravachol] vs 13.2% with placebo) in cardiovascular death or nonfatal MI and a 31% risk reduction in stroke (3.8% with pravastatin vs 2.6% with placebo).

The observed reduction in the rate of symptomatic heart failure supports the pleiotropic quality of statin therapy. There is increasing clinical evidence of reduced systemic vascular inflammation and enhanced endothelial function with statin therapy. In the full version of the current study, a significant reduction in C-reactive protein (CRP) was observed in the statin-treated patients. The early initiation of statin therapy likely enhances positive ventricular remodeling after acute MI and thereby reduces the development of heart failure.

Unique to this study was the inclusion of patients treated with primary PCI and stent placement. Unfortunately, in this era of rapid biomedical development, randomized controlled trials tend to lag behind current medical practice. In this study, bare metal stents were used, whereas the vast majority of PCIs are currently conducted using drug-eluting stents. There was no difference in the rate of PCI in the infarct-related lesion, despite a significant reduction in CRP. Although statin therapy reduces atherosclerotic plaque burden and vascular inflammation, the pathogenesis of intimal hyperplasia and in-stent thrombosis is more complex than atherosclerosis.

In addition to antiplatelet therapy, all patients with acute MI and ACS should probably be treated with aggressive lipid-lowering therapy. Current American Heart Association/ American College of Cardiology guidelines for secondary prevention in patients with coronary heart disease recommend targeting low-density lipoprotein (LDL) cholesterol levels below 100 mg/dL, triglyceride levels below 150 mg/dL, and non– high-density lipoprotein cholesterol levels below 130 mg/dL, with an optional LDL cholesterol level of below 70 mg/dL in persons with a recent ACS event, a difficult-to-control risk factor, diabetes, or multiple components of the metabolic syndrome.⁵ Clearly, all cardiovascular specialists need to be very aggressive with a comprehensive “ABC” approach, which includes Antiplatelet therapy, Blood pressure control, Cholesterol lowering, and Dietary and Exercise instruction in any patient with an acute presentation of unstable coronary disease, as well as in those with documented stable atherosclerotic vascular disease.⁶

References
1. Sakamoto T, Kojima S, Ogawa H, et al. Effects of early statin treatment on symptomatic heart failure and ischemic events after acute myocardial infarction in Japanese. Am J Cardiol. 2006; 97(18):1165-1171.

2. Schwartz GG, Olsson AG, Ganz P, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. JAMA. 2001; 285(13):1711-1718.

3. Briel M, Schwartz GG, Thompson PL, et al. Effects of early treatment with statins on short-term clinical outcomes in acute coronary syndromes: a meta-analysis of randomized controlled trials. JAMA. 2006; 295(17):2046-2056.

4. 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(14):1001-1009.

5. Smith SC, Allen J, Blair SN, et al. AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 Update. Circulation. 2006; 113(19):2363-2372.

6. Gluckman TH, Sachdev M, Schulman SP, et al. A simplified approach to the management of non-ST-segment elevation acute coronary syndromes. JAMA. 2005; 293(17):349-357.