Efficacy and tolerability of a generic and a branded formulation of atorvastatin 20 mg/d in hypercholesterolemic Korean adults at high risk for cardiovascular disease: a multicenter, prospective, randomized, double-blind, double-dummy clinical trial.

BACKGROUND: The reduction in plasma LDL-C concentrations with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin) therapy has been reported to reduce cardiovascular risk and mortality in individuals with or without preexisting coronary artery disease and elevated LDL-C concentrations. Atorvastatin is a statin used for lowering LDL-C concentrations. A generic formulation of atorvastatin is being developed in Korea. This study was undertaken for the purposes of marketing the generic formulation. OBJECTIVE: This study was designed to compare the efficacy and tolerability of a generic formulation of atorvastatin 20 mg/d versus a branded formulation at the same dosage in hypercholesterolemic Korean adults at high risk for cardiovascular events. METHODS: This 8-week, multicenter, randomized, double-blind, double-dummy study was conducted at 10 clinical centers in Korea between September 2008 and May 2009. Male and female patients aged 20 to 85 years at high risk for cardiovascular events (defined as an elevated LDL-C concentration [≥100 mg/dL]) were enrolled. Eligible patients were randomly assigned to receive generic or branded atorvastatin 20 mg once daily for 8 weeks. The primary end point was the percentage change from baseline to 8 weeks in LDL-C concentration. Secondary end points were the percentage changes from baseline in total cholesterol (TC), triglycerides (TG), HDL-C, apolipoprotein (apo) A1 and B, and high-sensitivity C-reactive protein concentrations; small, dense LDL (sdLDL) fraction; and tolerability. Tolerability was assessed using physical examination, laboratory testing, and by recording adverse events (AEs) at each visit. An additional secondary end point was the proportion of patients who achieved an LDL-C goal of <100 mg/dL. RESULTS: A total of 244 patients were randomized to treatment, and 33 patients were withdrawn from the study (9 patients did not receive the study medication, 11 patients due to AEs, and 13 patients due to withdrawal of consent). A total of 211 patients completed the study (50.7% male; 100% Asian; mean [SD] age, 61.7 [9.2] years) (106 patients in the group that received Accepted for publication October 5, 2010. the generic formulation and 105 patients in the group that received the branded formulation). LDL-C concentrations were reduced from the baseline by 44% and 46% after 8 weeks of treatment with the generic and branded formulations, respectively (P = NS). The percentage changes from baseline to study end in HDL-C, TC, TG, apo A1, apo B, and hsCRP concentrations and sdLDL fraction the proportions of patients who achieved the LDL-C goal between the 2 groups did not reach statistical significance. The most commonly reported events were hepatobiliary laboratory abnormality (1.7%), general somatic discomfort (1.7%), and epigastric pain (0.8%) in the group that received the generic formulation, and myalgia (1.7%), epigastric pain (0.9%), and elevation of creatinine phosphokinase (0.9%) in the group that received the branded formulation. No serious AEs were reported in either group. CONCLUSIONS: After 8 weeks of treatment, the differences in the LDL-C-lowering effects between the generic and branded formulations of atorvastatin 20 mg/d did not reach statistical significance in these Korean patients at high risk for cardiovascular events. Both formulations were generally well tolerated.

Acute and chronic effects of cigarette smoking on arterial stiffness.

OBJECTIVES: Pulse wave velocity (PWV) is an indicator of arterial stiffness, especially in the aorta, and a marker for vascular damage. Smoking is reported to increase arterial stiffness. We examined the acute and chronic effects of smoking on arterial stiffness by measuring brachial--ankle PWV (baPWV) using an oscillometric method (VP 1000, Colin Co., Komaki, Japan). METHODS: All healthy male subjects (chronic smokers, n=40, 30.3 years old vs non-smokers, n=40, 28.3 years old) smoked two cigarettes (nicotine 1.5 mg) within 10 min and measured blood pressure (BP), heart rate and baPWV at baseline, 5, 15, 30, 45 and 60 min and compared with controls (n=20, 29.3 years old). RESULTS: Systolic BP was higher in chronic smokers than non-smokers or controls. Smoking increased the systolic and diastolic BP and heart rate significantly at 5 min in both chronic smokers and non-smokers as compared with baseline levels or controls (respectively, p<0.001) and returned to baseline level at 15 min. Pulse pressure did not increase significantly. baPWV increased significantly in both chronic smokers and non-smokers at 5 min (12.1--17.3 m/s vs 11.1--12.7 m/sec, respectively) and remained higher for 30 min compared with controls (p<0.001). Smoking increased baPWV to a greater extent in chronic smokers than in non-smokers (p<0.01). CONCLUSION: Acutely, cigarette smoking increased BP, heart rate and baPWV in chronic smokers and non-smokers. These effects were more prominent in chronic smokers than in non-smokers. These findings suggest that cigarette smoking have deleterious effects on cardiovascular system by stiffening arteries.