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
Division of Cardiology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea. Clinical Therapeutics
(Impact Factor: 2.73).
10/2010; 32(11):1896-905. DOI: 10.1016/j.clinthera.2010.10.004
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.
Available from: Robert A Hegele
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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.
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.
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.
Substituting generic for proprietary atorvastatin in lipid clinic patients was not associated with significant changes in efficacy, adverse events, or patient management.
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ABSTRACT: Atorvastatin is one of the most widely prescribed drugs and the most widely prescribed statin in the world. It is therefore important to know the dose-related magnitude of effect of atorvastatin on blood lipids.
To quantify the dose-related effects of atorvastatin on blood lipids and withdrawals due to adverse effects (WDAE).
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library Issue 4, 2011, MEDLINE (1966 to November 2011), EMBASE (1980 to November 2011), ISI Web of Science (1899 to November 2011) and BIOSIS Previews (1969 to November 2011). No language restrictions were applied.
Randomised controlled and uncontrolled before-and-after trials evaluating the dose response of different fixed doses of atorvastatin on blood lipids over a duration of 3 to 12 weeks.
Two review authors independently assessed trial quality and extracted data. WDAE information was collected from the placebo-controlled trials.
Two hundred fifty-four trials evaluated the dose-related efficacy of atorvastatin in 33,505 participants. Log dose-response data revealed linear dose-related effects on blood total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides. Combining all the trials using the generic inverse variance fixed-effect model for doses of 10 to 80 mg/day resulted in decreases of 36% to 53% for LDL-cholesterol. There was no significant dose-related effects of atorvastatin on blood high-density lipoprotein (HDL)-cholesterol. WDAE were not statistically different between atorvastatin and placebo for these short-term trials (risk ratio 0.99; 95% confidence interval 0.68 to 1.45).
Blood total cholesterol, LDL-cholesterol and triglyceride lowering effect of atorvastatin was dependent on dose. Log dose-response data was linear over the commonly prescribed dose range. Manufacturer-recommended atorvastatin doses of 10 to 80 mg/day resulted in 36% to 53% decreases of LDL-cholesterol. The review did not provide a good estimate of the incidence of harms associated with atorvastatin because of the short duration of the trials and the lack of reporting of adverse effects in 37% of the placebo-controlled trials.
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