Publications

CONTEXT

Statin drugs reduce both atherogenic lipoproteins and cardiovascular morbidity and mortality. However, the optimal strategy and target level for lipid reduction remain uncertain.

OBJECTIVE

To compare the effect of regimens designed to produce intensive lipid lowering or moderate lipid lowering on coronary artery atheroma burden and progression.

DESIGN, SETTING, AND PATIENTS

Double-blind, randomized active control multicenter trial (Reversal of Atherosclerosis with Aggressive Lipid Lowering [REVERSAL]) performed at 34 community and tertiary care centers in the United States comparing the effects of 2 different statins administered for 18 months. Intravascular ultrasound was used to measure progression of atherosclerosis. Between June 1999 and September 2001, 654 patients were randomized and received study drug; 502 had evaluable intravascular ultrasound examinations at baseline and after 18 months of treatment.

INTERVENTIONS

Patients were randomly assigned to receive a moderate lipid-lowering regimen consisting of 40 mg of pravastatin or an intensive lipid-lowering regimen consisting of 80 mg of atorvastatin.

MAIN OUTCOME MEASURES

The primary efficacy parameter was the percentage change in atheroma volume (follow-up minus baseline).

RESULTS

Baseline low-density lipoprotein cholesterol level (mean, 150.2 mg/dL [3.89 mmol/L] in both treatment groups) was reduced to 110 mg/dL (2.85 mmol/L) in the pravastatin group and to 79 mg/dL (2.05 mmol/L) in the atorvastatin group (P<.001). C-reactive protein decreased 5.2% with pravastatin and 36.4% with atorvastatin (P<.001). The primary end point (percentage change in atheroma volume) showed a significantly lower progression rate in the atorvastatin (intensive) group (P =.02). Similar differences between groups were observed for secondary efficacy parameters, including change in total atheroma volume (P =.02), change in percentage atheroma volume (P<.001), and change in atheroma volume in the most severely diseased 10-mm vessel subsegment (P<.01). For the primary end point, progression of coronary atherosclerosis occurred in the pravastatin group (2.7%; 95% confidence interval [CI], 0.2% to 4.7%; P =.001) compared with baseline. Progression did not occur in the atorvastatin group (-0.4%; CI -2.4% to 1.5%; P =.98) compared with baseline.

CONCLUSIONS

For patients with coronary heart disease, intensive lipid-lowering treatment with atorvastatin reduced progression of coronary atherosclerosis compared with pravastatin. Compared with baseline values, patients treated with atorvastatin had no change in atheroma burden, whereas patients treated with pravastatin showed progression of coronary atherosclerosis. These differences may be related to the greater reduction in atherogenic lipoproteins and C- reactive protein in patients treated with atorvastatin.

Chronic obstructive pulmonary disease (COPD) is the most common lung disease, carrying a significant mortality and morbidity. None of the therapeutic interventions currently available alter the progression of the disease. As our understanding of the basic mechanisms of alveolar destruction and airflow limitation improves, new targets are identified that may eventually result in treatment options which will affect the progression of this disease. In this review, we discuss some of the novel therapeutic options recently developed that may have an impact on the management of COPD. Future directions in research and development of pharmacological agents based on improved understanding of COPD are also discussed.