title: Development of tachyphylaxis among patients taking HMG CoA reductase inhibitors.
abstract: The purpose of this study was to determine if long-term use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (atorvastatin, fluvastatin, lovastatin, pravastatin, or simvastatin) resulted in tachyphylaxis (a decreasing response to a physiologically active agent). To determine this, the charts of 254 patients treated with statins from the years 1996 to 1998 were retrospectively reviewed. During treatment, the low-density lipoprotein (LDL) cholesterol levels of patients were followed for a minimum of 300 days. To characterize LDL cholesterol changes during statin therapy, linear and nonlinear kinetic models were generated. Tachyphylaxis, defined as a positive slope of LDL cholesterol over time, after maximum LDL cholesterol reduction, was identified in patients treated with atorvastatin at exposure doses of 10 or 20 mg/day. All other statins, at all doses reviewed, showed no [corrected] evidence of tachyphylaxis. LDL cholesterol tachyphylaxis appeared to be a unique response to prolonged use of long half-life atorvastatin therapy at exposure dosages.
authors.affiliation: Lipoprotein and Metabolic Disorders Institute, Raleigh, North Carolina, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Cromwell
authors.forename: P E
authors.initials: PE
authors.lastname: Ziajka
mesh_terms: D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000009:adverse effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007211:Indoles / Q000009:adverse effects; D016018:Least-Squares Analysis; D016014:Linear Models; D008148:Lovastatin / Q000009:adverse effects; D017711:Nonlinear Dynamics; D017035:Pravastatin / Q000009:adverse effects; D011758:Pyrroles / Q000009:adverse effects; D012189:Retrospective Studies; D019821:Simvastatin / Q000009:adverse effects; D013618:Tachyphylaxis; D013997:Time Factors
chemical_list: D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077340:Fluvastatin; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin