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.
ABSTRACT 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.
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.
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.
A total of 244 patients were randomized to treatment, and 33 patients were withdrawn from the study (9 patients did not receive the study medication, 11 patients due to AEs, and 13 patients due to withdrawal of consent).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.
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.
- SourceAvailable from: Robert A Hegele[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND: The loss of patent protection for proprietary statins offers affordability advantages to payers, but some clinicians still question the efficacy of generic formulations in real-world clinical applications. METHODS: In this retrospective cohort study, we examined the effects of generic atorvastatin substitution on relevant biochemical parameters in 85 dyslipidemic patients who had been previously maintained on stable doses of proprietary atorvastatin from 2009 to 2011. For comparison, we studied 143 patients who were continuously prescribed stable doses of rosuvastatin, which was only available in its proprietary formulation over the same time period. RESULTS: We found that substitution of generic for proprietary atorvastatin was not associated with significant changes in plasma levels of total or low-density lipoprotein cholesterol, or triglycerides, but was associated with a small but significant increase in high-density lipoprotein cholesterol. Plasma levels of aspartate aminotransferase and creatine kinase were also unchanged. Additionally, the changeover to generic atorvastatin was not associated with increased switching to another statin or more frequent changes in other lipid-lowering medications compared with the proprietary rosuvastatin group. CONCLUSIONS: Substituting generic for proprietary atorvastatin in lipid clinic patients was not associated with significant changes in efficacy, adverse events, or patient management.The Canadian journal of cardiology 07/2012; · 3.12 Impact Factor
- The Canadian journal of cardiology 10/2012; · 3.12 Impact Factor