Comparison of effectiveness of statin monotherapy versus statin and niacin combination therapy in primary prevention and effects on calcified plaque burden

Abstract

T combination of a statin and niacin is increasingly being prescribed for treatment of combined lipid disorders, and has recently been shown to produce a dramatic decrease in clinical events and atherosclerosis progression, measured by quantitative coronary angiography in secondary prevention patients.1 This study was designed to determine whether calcified plaque progression, determined by electron beam tomography (EBT), differs in groups of primary prevention patients treated with statins alone compared with statin and niacin combination therapy. In addition, the correlations between the change in calcified plaque burden and changes in low-density lipoprotein (LDL) particle size and subgroups were evaluated. • • • One hundred sixty-two consecutive asymptomatic patients with EBT evidence for subclinical atherosclerosis, who were treated with a statin alone or in combination with niacin (Niaspan; Kos Pharmaceuticals, Miami, Florida) and underwent repeat EBT evaluation, comprised the patient population. This was an observational study; serial EBT evaluation and lipidlowering agents and doses employed were chosen by the treating physicians based on clinical considerations, and not according to criteria set by the investigators. All patients gave consent for their data to be used in subsequent analyses. No patient had a history of clinical coronary artery disease. Hypertension was defined as the current or recommended use of antihypertensive medications for blood pressure control. Smoking was defined as current tobacco usage, and diabetes was defined as the current or recommended use of diet or medication to decrease blood sugar. Family history of coronary artery disease was defined as established disease in first-degree male relatives 56 years of age or female relatives 66 years of age. Body mass index was calculated as weight (kilograms)/height (meters squared). Lipid measurements were obtained at the time of both EBT evaluations. EBT was performed using an Imatron C-150 scanner (GE/Imatron, South San Francisco, California) and previously described acquisition protocol.2 The coronary artery calcium score was calculated with the Agatston method.3 The calcium volume score, a parameter of plaque burden that is density independent, was calculated according to the method of Callister et al.4 The calcium percentile, an age and gender corrected index of plaque prematurity, was derived from the University of Illinois asymptomatic patient database. EBT studies done before and after treatment were reviewed side-by-side for comparability of analysis by an experienced observer (HSH), blinded to the treatment effects. Changes in coronary calcium and calcium volume scores were calculated on an absolute basis and as a percent change per year. To avoid skewing the data by large percentage changes in a few patients with lower scores, the percent change per year for the treated and untreated groups was calculated by dividing the mean annualized change by the mean baseline values for the groups as a whole, rather than by the mean of the percent change per year for each patient. Fasting plasma lipid and lipoprotein cholesterol concentrations were determined by the methods of the Lipid Research Clinics in all patients.5 In 53 patients treated with niacin, densitometric measurements of LDL subspecies were carried out using custom made, triple gradient (S3), 2% to 16% polyacrylamide gradient gel electrophoresis (S3GGE) of plasma samples (Berkeley HeartLab, Burlingame, California).6 LDL peak particle diameter was measured and LDL subclass distribution was determined in 3 large regions (I, IIa, IIb) and 4 small regions (IIIa, IIIb, IVa, IVb). LDL subclass pattern was classified based on LDL peak particle diameter, number and position of peaks, and From the Beth Israel Medical Center, New York, New York; and Kronos Longevity Research Institute, Phoenix, Arizona. Dr. Hecht’s address is: PO Box 450, 9 Woodland Road, Brookside, New Jersey 07926. E-mail: hhecht@aol.com. Manuscript received July 22, 2002; revised manuscript received and accepted September 20, 2002. TABLE 1 Patient Characteristics