Paul D Thompson1, John Rubino2, Matthew J Janik3, Diane E MacDougall4, Scott J McBride5, Janice R Margulies4, Roger S Newton4. 1. Department of Cardiology, Hartford Hospital, Hartford, CT, USA. Electronic address: paul.thompson@hhchealth.org. 2. PMG Research of Raleigh, Raleigh, NC, USA. 3. Department of Cardiology, Wilmington Health, Wilmington, NC, USA; PMG Research of Wilmington, Wilmington, NC, USA. 4. Esperion Therapeutics, Inc., Ann Arbor, MI, USA. 5. United BioSource Corporation, Ann Arbor, MI, USA.
Abstract
BACKGROUND: Once-daily, oral ETC-1002 reduces low-density lipoprotein cholesterol (LDL-C) and has beneficial effects on other cardiometabolic risk factors but has not been examined in statin intolerant patients. OBJECTIVES: To study the efficacy and safety of ETC-1002 (a novel LDL-C-lowering agent) in patients with hypercholesterolemia and a history of statin intolerance. METHODS:Patients intolerant to at least 1 statin were entered into this multicenter, double-blind, 8-week trial. Participants were required to have a history of muscle complaints that developed during statin treatment and resolved within 4 weeks of statin discontinuation. Patients (n = 56) were randomized in a 2:1 ratio to ETC-1002 60 mg daily or placebo. The ETC-1002 dose was increased at 2-week intervals to 120 mg, 180 mg, and 240 mg. The primary end point was the percentage change from baseline to week 8 in calculated LDL-C. RESULTS:ETC-1002 reduced LDL-C 28.7% more than placebo (95% confidence interval, -35.4 to -22.1; P < .0001). ETC-1002 significantly reduced non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. Triglycerides and high-density lipoprotein cholesterol did not change with ETC-1002 treatment. Sixty-two percent of patients receiving ETC-1002 and none in the placebo group achieved the 2004 National Cholesterol Education Program Adult Treatment Panel III LDL-C goal (P < .0001). Muscle-related adverse events occurred with similar frequency in the placebo and ETC-1002 treatment groups, causing no discontinuations in ETC-1002-treated patients. CONCLUSIONS:ETC-1002 appears to be effective at reducing LDL-C and was well tolerated in patients with statin-associated muscle complaints. Longer and larger studies are required to confirm the absence of muscle side effects.
RCT Entities:
BACKGROUND: Once-daily, oral ETC-1002 reduces low-density lipoprotein cholesterol (LDL-C) and has beneficial effects on other cardiometabolic risk factors but has not been examined in statin intolerant patients. OBJECTIVES: To study the efficacy and safety of ETC-1002 (a novel LDL-C-lowering agent) in patients with hypercholesterolemia and a history of statin intolerance. METHODS:Patients intolerant to at least 1 statin were entered into this multicenter, double-blind, 8-week trial. Participants were required to have a history of muscle complaints that developed during statin treatment and resolved within 4 weeks of statin discontinuation. Patients (n = 56) were randomized in a 2:1 ratio to ETC-1002 60 mg daily or placebo. The ETC-1002 dose was increased at 2-week intervals to 120 mg, 180 mg, and 240 mg. The primary end point was the percentage change from baseline to week 8 in calculated LDL-C. RESULTS:ETC-1002 reduced LDL-C 28.7% more than placebo (95% confidence interval, -35.4 to -22.1; P < .0001). ETC-1002 significantly reduced non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. Triglycerides and high-density lipoprotein cholesterol did not change with ETC-1002 treatment. Sixty-two percent of patients receiving ETC-1002 and none in the placebo group achieved the 2004 National Cholesterol Education Program Adult Treatment Panel III LDL-C goal (P < .0001). Muscle-related adverse events occurred with similar frequency in the placebo and ETC-1002 treatment groups, causing no discontinuations in ETC-1002-treated patients. CONCLUSIONS:ETC-1002 appears to be effective at reducing LDL-C and was well tolerated in patients with statin-associated muscle complaints. Longer and larger studies are required to confirm the absence of muscle side effects.
Authors: Robert A Hegele; Samuel S Gidding; Henry N Ginsberg; Ruth McPherson; Frederick J Raal; Daniel J Rader; Jennifer G Robinson; Francine K Welty Journal: Arterioscler Thromb Vasc Biol Date: 2015-09-16 Impact factor: 8.311
Authors: Satyawan B Jadhav; Ryan L Crass; Sunny Chapel; Michael Kerschnitzki; William J Sasiela; Maurice G Emery; Benny M Amore; P Hugh R Barrett; Gerald F Watts; Alberico L Catapano Journal: Eur Heart J Cardiovasc Pharmacother Date: 2022-09-03