EFFECT OF LOVASTATIN ON EARLY CAROTID ATHEROSCLEROSIS AND CARDIOVASCULAR EVENTS

Background HMG CoA reductase inhibitors (or statins), a new class of l ipid-lowering compounds, have raised expectations for more widespread use than that of the older lipid-lowering drugs. Not only are they mor e effective in lowering LDL cholesterol, but they are better tolerated as well. No data exist concerning the effect of statins on early caro tid atherosclerosis and clinical events in men and women who have mode rately elevated LDL cholesterol levels but are free of symptomatic car diovascular disease. Methods and Results Lovastatin (20 to 40 mg/d) or its placebo was evaluated in a double-blind, randomized clinical tria l with factorial design along with warfarin (1 mg/d) or its placebo. T his report is limited to the lovastatin component of the trial. Daily aspirin (81 mg/d) was recommended for everyone. Enrollment included 91 9 asymptomatic men and women, 40 to 79 years old, with early carotid a therosclerosis as defined by B-mode ultrasonography and LDL cholestero l between the 60th and 90th percentiles. The 3-year change in mean max imum intimal-medial thickness (IMT) in 12 walls of the carotid arterie s was the primary outcome; change in single maximum IMT and incidence of major cardiovascular events were secondary outcomes. LDL cholestero l fell 28%, from 156.6 mg/dL at baseline to 113.1 mg/dL at 6 months (P < .0001), in the lovastatin groups and was largely unchanged in the l ovastatin-placebo groups. Among participants not on warfarin, regressi on of the mean maximum IMT was seen after 12 months in the lovastatin group compared with the placebo group; the 3-year difference was stati stically significant (P = .001). A larger favorable effect of lovastat in was observed for the change in single maximum IMT but was not stati stically significant (P = .12). Five lovastatin-treated participants s uffered major cardiovascular events-coronary heart disease mortality, nonfatal myocardial infarction, or stroke - versus 14 in the lovastati n-placebo groups (P = .04). One lovastatin-treated participant died, c ompared with eight on lovastatin-placebo (P = .02). Conclusions In men and women with moderately elevated LDL cholesterol, lovastatin revers es progression of IMT in the carotid arteries and appears to reduce th e risk of major cardiovascular events and mortality. Results from ongo ing large-scale clinical trials may further establish the clinical ben efit of statins.