Related articles on this website: In the Current Literature section, Use of Lipid-Lowering Medications at Discharge in Patients With Acute Myocardial Infarction: Data From the National Registry of Myocardial Infarction 3 Fonarow GC, French WJ, Parsons LS, et al. Circulation. 2001;103:38-44. Early Statin Treatment Following Acute Myocardial Infarction and 1-Year Survival Stenestrand U, Wallentin L, for the Swedish Register of Cardiac Intensive Care (RIKS-HIA). JAMA. 2001;285:430-436.

Figure. Characteristics of Plaques Prone to Rupture

Libby P. Circulation. 1995;91:2844-2850

The Benefits of Lipid Lowering in ACS
In secondary-prevention trials such as CARE (Cholesterol and Recurrent Events),² LIPID (Long-term Intervention with Pravastatin in Ischaemic Disease),³ and 4S (Scandinavian Simvastatin Survival Study),⁴ treatment with statins as part of long-term follow-up in post-ACS patients has been shown to reduce the risks for recurrent MI, cerebrovascular events, and death from any cause. The AVERT (Atorvastatin Versus Revascularization Treatments) study^5,6 noted that treatment with 80 mg/day of atorvastatin was associated with a significantly longer time to the first ischemic event (P=0.03) compared with invasive treatment, thus making a case for medical therapy as an important complement for surgical interventions.
   Researchers are now studying the effects of aggressive lipid modification in the early acute phase of coronary events on the risk for future events (see next page). The Swedish Registry Study⁷ provides intriguing observational data showing that initiating treatment with HMG-CoA reductase inhibitors (statins) earlier in the management of coronary patients improves survival, but this finding requires confirmation in a prospective, placebo-controlled interventional study. The MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering) trial will provide additional insights when results become available.

Statins and ACS
The attention on statins and the acute phase of coronary disease is justified by the improved understanding of the etiology of atherosclerotic disease. We know now that the coronary lesions that put the patient at greatest risk for an event are often not those that cause the greatest stenosis, but those that are only mildly to moderately stenotic with lipid-rich cores and thin fibrous caps (see Figure). The latter kind of lesion is vulnerable to plaque rupture with subsequent thrombosis that produces an ACS.⁸
   Inflammation and endothelial dysfunction appear to play key roles in producing this high-risk plaque. Statin therapy reduces markers of inflammation, such as C-reactive protein,⁹ and statins appear to improve endothelial vasodilatation in atherosclerotic vessels, possibly through their positive effect on expression of the powerful vasodilator nitric oxide.¹⁰ These antiinflammatory and endothelium-normalizing effects may contribute to a reduction in the risk for plaque rupture, thus illuminating potential mechanisms for the benefits observed with statins in clinical trials. Plaque stabilization may be especially relevant in the early, unstable phase following an acute event,¹¹ although whether these effects are dependent or independent of the lipid lowering achieved with statins is controversial.

Looking to the Future of ACS Management
Researchers continue to explore strategies to further improve ACS outcomes. Currently being pursued are methods to restore and maintain coronary flow at the site of the vulnerable lesion; ways to reduce infarct size, reperfusion injury, and postischemic dysfunction; and strategies to reduce recurrent ischemic events by stabilizing underlying coronary arteriopathy. Thanks to the number and scope of these investigations, new life-saving techniques will continually be added to standard clinical management.¹¹
   Some experts believe that optimal therapy for coronary heart disease might include a combination of a low-fat diet or a Mediterranean diet and endothelial passivation by means of angiotensin-converting enzyme inhibitors, lipid-lowering drugs, antioxidants, antiplatelet agents, and antiinflammatory agents.¹²
   Based on the emerging data, the future for improved ACS management looks promising. Eventually, a sophisticated multipronged strategy that will optimize patient outcomes following an acute coronary event may arise.