REVERSAL
Reversal of Atherosclerosis with Aggressive Lipid Lowering

Presented at the American Heart Association Scientific Sessions, Nov 2003

Intensive lipid-lowering treatment with atorvastatin completely halted the progression of atherosclerosis, whereas a moderate lipid-lowering regimen of pravastatin was associated with continued atherosclerosis progression

Background

Statins have shown consistent morbidity and mortality benefits in placebo-controlled trials. However, virtually no data are available comparing the relative benefits of statins on atherosclerosis or clinical outcomes. Prior angiographic trials have shown reduced progression of coronary atherosclerosis with statin therapy, but neither an absence of plaque progression nor plaque regression has been demonstrated. In addition, there has been no large, prospective trial to assess the effects of statin therapy using more contemporary imaging methods such as intravascular ultrasound (IVUS).

Aim

To compare effects of an intensive lipid-lowering regimen using atorvastatin with more moderate lipid-lowering treatment using pravastatin on the progression of coronary atherosclerosis using IVUS

Patients and Methods

• 654 patients enrolled at 34 centers
• Symptomatic CAD documented with coronary angiography ( > 20% stenosis)
• Study groups: Pravastatin 40 mg Vs Atorvastatin 80 mg
• Study duration: 18 months
• Atheroma volume computed using IVUS to assess effect on atherosclerosis

Results

• Atorvastatin halted the process of atherosclerosis, while atherosclerosis progression continued in the pravastatin group

• Atorvastatin caused a greater reduction in LDL, total cholesterol and triglycerides as compared to placebo

• Greater percentage of patients reached NCEP goal in the atorvastatin group

• Even in the 67% patients in whom pravastatin treatment attained LDL goal (mean 88 mg/dl), atherosclerotic progression occurred (%change in atheroma volume=1.9)

• Many individual patients in atorvastatin group showed major plaque regression

• Reduction in CRP was significantly greater with atorvastatin

• No differences in ALT, AST or CK elevations were observed between treatment groups. No clinical myopathy was observed in either group

Conclusion

• Maximally intensive lipid lowering therapy can completely halt the atherosclerotic disease process

• Intensive statin treatment is warranted in secondary prevention, particularly for patients at high risk of morbid events

• Differences between the two statins may at least be partially related to greater reduction in CRP with atorvastatin

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