Hypercholesterolemia: Blasetto JW

Fox KM, Gandhi SK, Ohsfeldt RL, Blasetto JW, Bays HE. · University of Maryland School of Medicine, Department of Epidemiology & Preventive Medicine, Baltimore, MD, USA. · Curr Med Res Opin. · Pubmed #17655813 No free full text.

Abstract: OBJECTIVE: To compare effectiveness of rosuvastatin (RSV) with other statins on lowering low-density lipoprotein cholesterol (LDL-C) and LDL-C goal attainment among patients with type 1 or type 2 diabetes mellitus. METHODS: A retrospective study using US General Electric Medical Systems (GEMS) database of patients with diabetes mellitus (ICD9 code = 250, prescription for anti-diabetic medication or fasting blood glucose level > or = 126 mg/dL in the 12 months preceding statin therapy) treated across clinical practices in the US, who were newly prescribed statin therapy during August 2003-March 2006, was conducted. Multivariate linear and logistic regression models were used for analyzing prescription data with baseline LDL-C, age, gender, smoking, very high CHD risk, systolic blood pressure, and statin duration as covariates. RESULTS: Of 4754 diabetes mellitus patients, 5% were prescribed RSV, 59% atorvastatin (ATV), 21% simvastatin (SMV), 5% pravastatin (PRV), 2% fluvastatin (FLV), and 7% lovastatin (LOV). RSV patients had significantly higher (p < 0.05) baseline mean LDL-C levels (138 vs. 117-131 mg/dL), lower average starting dose (11.7 vs. 17.0-63.7 mg) and were younger (p < 0.005) than patients on other statins (mean age 61 vs. 63-69 years). Percent LDL-C reduction was significantly greater (p < 0.0001) with RSV (28.4%) compared to ATV (22.5%), SMV (20.1%), PRV (13.7%), FLV (15.8%), and LOV (17.3%). A greater (p < 0.05) proportion of RSV diabetes patients attained LDL-C goal < 100 mg/dL (72.8%) vs. diabetes mellitus patients on other statins (36.8-67.4%). CONCLUSIONS: Rosuvastatin was more effective in lowering LDL-C and achieving LDL-C treatment goals in the diabetes mellitus population as compared to other statins in real-world clinical practice setting. Validating study results in a different diabetes population with dispensed statin prescriptions will help increase generalizability of study findings.

Jones PH, Hunninghake DB, Ferdinand KC, Stein EA, Gold A, Caplan RJ, Blasetto JW, Anonymous00173. · Section of Atherosclerosis and Lipid Research, Baylor College of Medicine, Houston, Texas 77030, USA. · Clin Ther. · Pubmed #15531001 No free full text.

Abstract: BACKGROUND: Non-high-density lipoprotein cholesterol (HDL-C), apolipoprotein (apo) B, and lipid and apolipoprotein ratios that include both atherogenic and antiatherogenic lipid components have been found to be strong predictors of coronary heart disease risk. OBJECTIVE: The goal of this study was to examine prospectively the effects of rosuvastatin, atorvastatin, simvastatin, and pravastatin across dose ranges on non-HDL-C, apo B, apo A-I, and total cholesterol (TC):HDL-C, low-density lipoprotein cholesterol (LDL-C):HDL-C, non-HDL-C:HDL-C, and apo B:apo A-I ratios in patients with hypercholesterolemia (LDL-C > or =160 mg/dL and <250 mg/dL and triglycerides <400 mg/dL) in the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial. METHODS: In this randomized, Multicenter, parallel-group, open-label trial (4522IL/0065), patients > or =18 years of age received rosuvastatin 10, 20, 40, or 80 mg; atorvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; or pravastatin 10, 20, or 40 mg for 6 weeks. Pairwise comparisons were prospectively planned and performed between rosuvastatin 10, 20, and 40 mg and milligram-equivalent or higher doses of comparators. RESULTS: A total of 2268 patients were randomized to the rosuvastatin 10- to 40-mg, atorvastatin, simvastatin, and pravastatin groups. Fifty-one percent of patients were women, the mean (SD) age was 57 (12) years, and 19% had a documented history of atherosclerotic disease. Over 6 weeks, rosuvastatin significantly reduced non-HDL-C, apo B, and all lipid and apolipoprotein ratios assessed, compared with milligram-equivalent doses of atorvastatin and milligram-equivalent or higher doses of simvastatin and pravastatin (all, P < 0.002). Rosuvastatin reduced non-HDL-C by 42.0% to 50.9% compared with 34.4% to 48.1% with atorvastatin, 26.0% to 41.8% with simvastatin, and 18.6% to 27.4% with pravastatin. Rosuvastatin reduced apo B by 36.7% to 45.3% compared with 29.4% to 42.9% with atorvastatin, 22.2% to 34.7% with simvastatin, and 14.7% to 23.0% with pravastatin. The highest increase in apo A-I (8.8%) was observed in the rosuvastatin 20-mg group, and this increase was significantly greater than in the atorvastatin 40-mg and 80-mg groups (both, P < 0.002). CONCLUSION: Rosuvastatin 10 to 40 mg was more efficacious in improving the lipid profile of patients with hypercholesterolemia than milligram-equivalent doses of atorvastatin and milligram-equivalent or higher doses of simvastatin and pravastatin.

Shepherd J, Packard C, Littlejohn TW, Walker J, Stein EA, Smith K, Kallend D, Blasetto JW. · Glasgow Royal Infirmary, Glasgow, Scotland, UK. · Curr Med Res Opin. · Pubmed #15462690 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy and safety of rosuvastatin in postmenopausal women with hypercholesterolemia who are receiving hormone replacement therapy (HRT) in a randomized, double-blind, placebo-controlled trial. METHODS: After a 6-week dietary lead-in period, 135 postmenopausal women who had been taking a stable HRT regimen for at least 3 months were randomized to receive rosuvastatin 5 mg, 10 mg or placebo for 12 weeks. Fasting levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG) were assessed at weeks 0, 2, 6, 10, and 12; apolipoprotein (Apo) B and Apo A-I were measured at weeks 0 and 12. RESULTS: Rosuvastatin 5 mg and 10 mg significantly reduced LDL-C by 38% (SE = 2.1) and 49% (SE = 2.1), respectively, compared with placebo (1% [SE = 2.1]; p < 0.001). TC, TG, Apo B, and all lipid ratios examined (LDL-C/HDL-C, TC/HDL-C, non-HDL-C/HDL-C, and Apo B/Apo A-I) were also reduced significantly by both rosuvastatin doses (p < 0.001). HDL-C levels increased significantly in the rosuvastatin groups (11% and 8% for 5 mg and 10 mg, respectively, vs. -0.5% for placebo; p < 0.001), as did Apo A-I levels (p < 0.05). The combination of rosuvastatin plus HRT was well tolerated with no apparent differences among treatments in the numbers or types of adverse events reported. CONCLUSIONS: Rosuvastatin 5 mg or 10 mg once daily is a well-tolerated and highly efficacious lipid-lowering therapy in postmenopausal women receiving HRT.

McKenney JM, Jones PH, Adamczyk MA, Cain VA, Bryzinski BS, Blasetto JW, Anonymous00190. · National Clinical Research, Richmond, Virginia, USA. · Curr Med Res Opin. · Pubmed #14687438 No free full text.

Abstract: In the Statin Therapies for Elevated Lipid Levels compared Across doses to Rosuvastatin (STELLAR) trial, the efficacy of rosuvastatin calcium (Crestor) was compared with that of atorvastatin (Lipitor), simvastatin (Zocor), and pravastatin (Pravachol) for lowering plasma low-density lipoprotein cholesterol (LDL-C) after 6 weeks of treatment. In this multicenter, parallel-group, open-label trial, adults with hypercholesterolemia were randomized to treatments with rosuvastatin 10, 20, 40, or 80 mg, atorvastatin 10, 20, 40, or 80 mg, simvastatin 10, 20, 40, or 80 mg, or pravastatin 10, 20, or 40 mg. Efficacy and safety results from this trial have been previously published. The additional analyses included in this report show that 53% (83/156) to 80% (125/157) of patients in the rosuvastatin 10- to 40-mg groups achieved LDL-C levels < 100 mg/dl (< 2.6 mmol/l), compared with 18% (28/158) to 70% (115/165) of patients who received atorvastatin, 8% (13/165) to 53% (86/163) of patients who received simvastatin, and 1% (1/160) to 8% (13/161) of patients who received pravastatin. Other additional analyses showed that more patients in the rosuvastatin 10- to 40-mg groups than in the comparator groups who were at high risk of coronary heart disease according to National Cholesterol Education Program Adult Treatment Panel (ATP) III, Joint European Societies, or Canadian guidelines achieved the LDL-C goals of < 100 mg/dl (< 2.6 mmol/l) (55% to 77% compared with 0 to 64%), < 3.0 mmol/l (< 116 mg/dl) (76% to 94% compared with 6% to 81%), and < 2.5 mmol/l (< 97 mg/dl) (47% to 69% compared with 0 to 53%), respectively. Results favoring rosuvastatin versus the comparators were also reported for patients: (a) who had triglycerides > or = 200mg/dl (> or = 2.3 mmol/l), and achieved both ATP III LDL-C and non-high-density lipoprotein cholesterol (non-HDL-C) goals (80% to 84% versus 15% to 84%); (b) overall who achieved the Canadian LDL-C goals of < 2.5 (< 97 mg/dl) to < 5.0 mmol/l (< 193 mg/dl) (85% to 91% versus 44% to 86%); and (c) who achieved all 3 Canadian goals for LDL-C, triglycerides (< 3.0 mmol/l [< 266 mg/dl] to < 2.0 mmol/l [< 177 mg/dl]), and the total cholesterol/high-density lipoproteincholesterol ratio (< 4 to < 7) (70% to 83% versus 35% to 79%).

Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, Cain VA, Blasetto JW, Anonymous00313. · Baylor College of Medicine, 6565 Fannin Avenue, A-601, Houston, TX 77030, USA. · Am J Cardiol. · Pubmed #12860216 No free full text.

Abstract: The primary objective of this 6-week, parallel-group, open-label, randomized, multicenter trial was to compare rosuvastatin with atorvastatin, pravastatin, and simvastatin across dose ranges for reduction of low-density lipoprotein (LDL) cholesterol. Secondary objectives included comparing rosuvastatin with comparators for other lipid modifications and achievement of National Cholesterol Education Program Adult Treatment Panel III and Joint European Task Force LDL cholesterol goals. After a dietary lead-in period, 2,431 adults with hypercholesterolemia (LDL cholesterol > or =160 and <250 mg/dl; triglycerides <400 mg/dl) were randomized to treatment with rosuvastatin 10, 20, 40, or 80 mg; atorvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; or pravastatin 10, 20, or 40 mg. At 6 weeks, across-dose analyses showed that rosuvastatin 10 to 80 mg reduced LDL cholesterol by a mean of 8.2% more than atorvastatin 10 to 80 mg, 26% more than pravastatin 10 to 40 mg, and 12% to 18% more than simvastatin 10 to 80 mg (all p <0.001). Mean percent changes in high-density lipoprotein cholesterol in the rosuvastatin groups were +7.7% to +9.6% compared with +2.1% to +6.8% in all other groups. Across dose ranges, rosuvastatin reduced total cholesterol significantly more (p <0.001) than all comparators and triglycerides significantly more (p <0.001) than simvastatin and pravastatin. Adult Treatment Panel III LDL cholesterol goals were achieved by 82% to 89% of patients treated with rosuvastatin 10 to 40 mg compared with 69% to 85% of patients treated with atorvastatin 10 to 80 mg; the European LDL cholesterol goal of <3.0 mmol/L was achieved by 79% to 92% in rosuvastatin groups compared with 52% to 81% in atorvastatin groups. Drug tolerability was similar across treatments.

Blasetto JW, Stein EA, Brown WV, Chitra R, Raza A. · AstraZeneca LP, Wilmington, Delaware 19850, USA. · Am J Cardiol. · Pubmed #12646336 No free full text.

Abstract: A total of 5 randomized, double-blind trials in patients with hypercholesterolemia were prospectively designed to allow pooling of plasma lipid data after 12 weeks of treatment. The purpose was (1) to compare rosuvastatin 5 and 10 mg with atorvastatin 10 mg (data from 3 of the 5 trials); (2) to compare rosuvastatin 5 and 10 mg with simvastatin 20 mg and pravastatin 20 mg (data from 2 of the 5 trials); and (3) to summarize overall efficacy and subset analyses of rosuvastatin data from all 5 trials. Rosuvastatin 5 mg (n = 390) and 10 mg (n = 389) reduced low-density lipoprotein (LDL) cholesterol significantly more than did atorvastatin 10 mg (n = 393) (41.9% and 46.7% vs 36.4%, both p <0.001). Treatment with rosuvastatin 5 mg (n = 240) and 10 mg (n = 226) also resulted in significantly greater reductions in LDL cholesterol compared with both simvastatin 20 mg (n = 249) and pravastatin 20 mg (n = 252) (40.6% and 48.1% vs 27.1% and 35.7%, all p <0.001). Significant differences favoring rosuvastatin 10 mg were also observed for total cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, apolipoprotein (apo) B, and apo A-I versus atorvastatin 10 mg, and for total cholesterol, HDL cholesterol, triglycerides, non-HDL cholesterol, and apo B versus simvastatin 20 mg and pravastatin 20 mg. Analyses of all the rosuvastatin 10 mg data (n = 615) from the 5 trials in subgroups defined by age > or =65 years, female sex, postmenopausal status, hypertension, atherosclerosis, type 2 diabetes, and obesity showed that rosuvastatin had consistent efficacy across patient subgroups.

Fox KM, Gandhi SK, Ohsfeldt RL, Blasetto JW, Davidson MH. · Department of Epidemiology & Preventive Medicine, School of Medicine, University of Maryland, Baltimore, MD, USA. · Clin Ther. · Pubmed #18158079 No free full text.

Abstract: BACKGROUND: Lipid management in clinical practice has been suboptimal with a significant proportion of patients not achieving recommended cholesterol levels. A reason for low goal attainment may be the limited use of upward dose titration. OBJECTIVE: The aim of this study was to determine if, in routine clinical practice, a lower rate of titration is observed among rosuvastatin patients who achieved the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) target low-density lipoprotein cholesterol (LDL-C) goals as compared with patients achieving the target LDL-C goals on other statins. METHODS: This retrospective database study included the patients, aged > or =18 years, of approximately 3000 physicians across the United States, who were newly prescribed statin treatment from August 2003 to May 2005. Patients were excluded if they started on a maximum dose of statin, were at LDL-C goal at baseline (no clinical reason for titrating), or on fluvastatin (<70 patients). Titration rate with rosuvastatin was compared with other statins. Multivariate logistic regression models adjusted for baseline LDL-C, coronary heart disease risk, treatment duration, and target LDL-C goal attainment. RESULTS: This study assessed 12,041 patients for upward titration. Of the 5955 eligible patients (mean age, 63 years; male, 47%), 7.2% were prescribed rosuvastatin, 63.5% atorvastatin, 15.3% simvastatin, 7.2% pravastatin, and 6.9% lovastatin. Overall, 4337 patients (72.8%) attained the NCEP ATP III target LDL-C goal. Mean duration of statin treatment was 188 days for rosuvastatin compared with 238 to 260 days for the other statins (all, P < 0.05). Among patients attaining the target LDL-C goal, significantly fewer rosuvastatin patients (8.3%) had titration compared with atorvastatin (17.0%), simvastatin (20.0%), pravastatin (20.7%), and lovastatin (23.5%) (all, P < 0.05). After adjusting for baseline characteristics, patients attaining the target LDL-C goal on other statins were significantly more likely to be titrated as compared with rosuvastatin (odds ratios, 2.0-3.3; P < 0.05). Lower titration rates for rosuvastatin patients were also observed in the total population (P < 0.05). CONCLUSION: Our study found that rosuvastatin patients who attained the NCEP ATP III target LDL-C goal had significantly lower titration rates than patients receiving other statins.