Treatment of Asymptomatic Adults With Elevated Coronary Calcium Scores With Atorvastatin, Vitamin C, and Vitamin E: The St. Francis Heart Study Randomized Clinical Trial

Abstract

We sought to determine whether lipid-lowering therapy and antioxidants retard the progression of coronary calcification and prevent atherosclerotic cardiovascular disease (ASCVD) events. The electron beam computed tomography-derived coronary calcium score predicts coronary disease events. Small, uncontrolled studies suggest that vigorous lipid-lowering therapy slows progression of coronary calcification and prevents coronary artery disease events, but controlled, scientific demonstration of these effects is lacking. We conducted a double-blind, placebo-controlled randomized clinical trial of atorvastatin 20 mg daily, vitamin C 1 g daily, and vitamin E (alpha-tocopherol) 1,000 U daily, versus matching placebos in 1,005 asymptomatic, apparently healthy men and women age 50 to 70 years with coronary calcium scores at or above the 80th percentile for age and gender. All study participants also received aspirin 81 mg daily. Mean duration of treatment was 4.3 years. Treatment reduced total cholesterol by 26.5% to 30.4% (p < 0.0001), low-density lipoprotein cholesterol by 39.1% to 43.4% (p < 0.0001), and triglycerides by 11.2% to 17.0% (p < or = 0.02) but had no effect (p = 0.80) on progression of coronary calcium score (Agatston method). Treatment also failed to significantly reduce the primary end point, a composite of all ASCVD events (6.9% vs. 9.9%, p = 0.08). Event rates were related to baseline calcium score (pre-specified analysis) and may have been reduced in a subgroup of participants with baseline calcium score >400 (8.7% vs. 15.0%, p = 0.046 [not a pre-specified analysis]). Treatment with alpha-tocopherol, vitamin C, and low doses of atorvastatin (20 mg once daily) did not affect the progression of coronary calcification. Treatment may have reduced ASCVD events, especially in subjects with calcium scores >400, but these effects did not achieve conventional levels of statistical significance.