Effect of individualizing starting doses of a statin according to baseline LDL-cholesterol levels on achieving cholesterol targets: The Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study

Abstract

Aims: To investigate whether selecting the starting dose of atorvastatin according to baseline and target (<2.6 mmol/L) LDL-cholesterol (LDL-C) values would allow high-risk subjects to achieve target LDL-C concentration within 12 weeks, with the initial dose or a single uptitration. Methods and results: Twelve-week, prospective, open-label trial that enrolled 2117 high-risk subjects (statin-free [SF] or statin-treated [ST]). Subjects with LDL-C >2.6 mmol/L (100 mg/dL) but ≤5.7 mmol/L (220 mg/dL) were assigned a starting dose of atorvastatin (10, 20, 40 or 80 mg/day) based on LDL-C and status of statin use at baseline, with a single uptitration at 6 weeks, if required. There was no washout for ST subjects. At study end, 80% of SF (82%, 82%, 83% and 72% with 10, 20, 40 and 80 mg, respectively) and 59% of ST (60%, 61% and 51% with 20, 40 and 80 mg, respectively) subjects reached LDL-C target. In the ST group, an additional 21-41% reduction in LDL-C was observed over the statin used at baseline. Atorvastatin was well tolerated. Conclusion: This study confirms that individualizing the starting dose of atorvastatin according to baseline and target LDL-C values (i.e. the required LDL-C reduction), allows a large majority of high-risk subjects to achieve target safely, within 12 weeks, with the initial dose or with a single titration.

Effect of atorvastatin on circulating hsCRP concentrations: A sub-study of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study

“…Subjects were also excluded if they suffered from significant hepatic or renal impairment, uncontrolled diabetes, uncontrolled hypertension, uncontrolled primary hypothyroidism, clinically relevant gastrointestinal disease, elevation of creatine kinase (CK) level, alcohol or other drug abuse, or any severe disease or surgical procedure within 3 months of screening. A complete description of inclusion and exclusion criteria has been published elsewhere [24].…”

“…One week after screening, subjects were assigned to 6 weeks of openlabel treatment with atorvastatin according to their baseline LDL-C level and prior statin use, followed by an additional 6 weeks of treatment, during which subjects who had not reached LDL-C targets, were titrated to the next highest dose of atorvastatin if possible [24]. SF subjects with a baseline LDL-C of 100-149 mg/dL (2.6-3.8 mmol/L), 150-159 (3.9-4.1 mmol/L), 160-169 (4.2-4.4 mmol/L) and 170-220 mg/dL (4.5-5.7 mmol/L) were assigned to 10, 20, 40 and 80 mg of atorvastatin, respectively.…”

“…SF subjects with a baseline LDL-C of 100-149 mg/dL (2.6-3.8 mmol/L), 150-159 (3.9-4.1 mmol/L), 160-169 (4.2-4.4 mmol/L) and 170-220 mg/dL (4.5-5.7 mmol/L) were assigned to 10, 20, 40 and 80 mg of atorvastatin, respectively. Based on comparative potency with other statins, a decision was made that subjects who were on statin therapy at baseline but whose LDL-C remained above target would receive double the atorvastatin dose for the same baseline LDL-C level as compared to their untreated counterparts (up to a maximum of 80 mg), without any washout period [24]. Subjects initially allocated to atorvastatin 80 mg who did not reach LDL-C targets, were continued at that dose and a more intense therapeutic lifestyle intervention (NCEP III step 2 diet or equivalent) was recommended [23].…”

“…The main ACTFAST study investigated the benefits of selecting the starting dose of atorvastatin based on baseline LDL-C and current CAD risk status [24]. As a sub-study to ACTFAST, we investigated the effect of atorvastatin 10, 20, 40 and 80 mg on circulating concentrations of hsCRP in subjects at high cardiovascular risk, including pre-specified subgroups of subjects with the metabolic syndrome or diabetes.…”

Lower is better: Implications of the Treating to New Targets (TNT) study for Canadian patients

“…In the REVERSAL study (14), atorvastatin 80 mg daily reduced LDL-C to 2.05±0.76 mmol/L from a baseline LDL-C level of 3.24 mmol/L to 5.44 mmol/L. The Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study (28) assigned patients a starting dose of atorvastatin according to the baseline LDL-C and status of statin usage. A further uptitration was made six weeks later if the LDL-C target had not been reached.…”