Clinical drug investigation

Regression or reduction in progression of atherosclerosis, and avoidance of coronary events, with lovastatin in patients with or at high risk of cardiovascular disease: a review.

PMID 17705568


HMG-CoA reductase inhibitors (statins) are the drugs of first choice for treating hypercholesterolaemia in order to prevent or slow the progression of coronary heart disease (CHD). Statins generally reduce the risk of CHD morbidity or mortality by about 30%. Lovastatin is effective in lowering plasma total cholesterol and low-density lipoprotein cholesterol levels, and is widely prescribed for both the primary and secondary prevention of CHD. In the major AFCAPS/TexCAPS primary prevention study of 6605 middle-aged or elderly men and women without symptomatic cardiovascular disease and with only moderately elevated serum lipids, treatment with lovastatin 20-40 mg once daily for a mean of 5.2 years significantly (p < 0.001) reduced the incidence of a first acute major cardiac event by 37% compared with placebo. In the smaller ACAPS study of 919 men and women who were asymptomatic for cardiovascular disease, but with evidence of early atherosclerosis, treatment with lovastatin for 3 years significantly (p = 0.001) slowed or reversed atherosclerosis compared with placebo, as measured by changes in the intimal-medial thickness of carotid arteries on B-mode ultrasound. Three randomised, controlled, secondary prevention trials have demonstrated that in patients with coronary artery disease, treatment with lovastatin 20-80 mg/day alone or in combination with colestipol for 2-2.5 years reduced the severity of stenosis and/or slowed or reversed the progression of atherosclerosis, as assessed by angiography. In the FATS study, the severity of stenosis after 2.5 years in recipients of lovastatin plus colestipol was reduced by 2.8% compared with placebo, while the frequency of lesion progression was halved and the frequency of lesion regression was tripled. Treatment with lovastatin for 2.2 years in the MARS study significantly reduced the mean percent diameter stenosis compared with placebo (p = 0.005) in patients with more severe stenosis, and also significantly (p = 0.002) reduced the mean global change score (indicating less progression). In the CCAIT study, lovastatin therapy for 2 years significantly improved coronary change scores (p < 0.01) and significantly reduced the incidence of new lesions (p = 0.001) compared with placebo. Across the primary and secondary prevention studies, lovastatin was shown to be similarly effective in women, the elderly, smokers and in subjects with hypertension, hypercholesterolaemia or type 2 diabetes mellitus. Therefore, the available data demonstrate that lovastatin provides significant lipid-modifying efficacy, slows progression or causes regression of atherosclerosis, and protects against acute cardiac events, in both those with and those without symptomatic CHD.