Christie M Ballantyne1, Maciej Banach2, G B John Mancini3, Norman E Lepor4, Jeffrey C Hanselman5, Xin Zhao5, Lawrence A Leiter6. 1. Department of Medicine, Baylor College of Medicine, One Baylor Plaza, BCM 285, Houston, TX, 77030, USA. Electronic address: cmb@bcm.edu. 2. Department of Hypertension, Medical University of Lodz, Zeromskiego 113, 90-549, Lodz, Poland. 3. Division of Cardiology, University of British Columbia, 2775 Laurel Street 10th Floor, Vancouver, V5Z 1M9, British Columbia, Canada. 4. David Geffen School of Medicine at UCLA and Cedars-Sinai Medical Center, Los Angeles, CA, USA; Westside Medical Associates of Los Angeles, 99 La Cienega Blvd. #203, Beverly Hills, CA, 90211, USA. 5. Clinical Development, Esperion Therapeutics, Inc., 3891 Ranchero Dr., Ann Arbor, MI, 48108, USA. 6. Division of Endocrinology & Metabolism, Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, 61 Queen St East #6121, Toronto, M5C 2T2, Ontario, Canada.
Abstract
BACKGROUND AND AIMS: Patients with hyperlipidemia who are unable to tolerate optimal statin therapy are at increased cardiovascular risk due to ongoing elevations in low-density lipoprotein cholesterol (LDL-C). The objective of CLEAR Tranquility (NCT03001076) was to evaluate the efficacy and safety of bempedoic acid when added to background lipid-modifying therapy in patients with a history of statin intolerance who require additional LDL-C lowering. METHODS: This phase 3, multicenter, randomized, double-blind, placebo-controlled study enrolled patients with a history of statin intolerance and an LDL-C ≥100 mg/dL while on stable lipid-modifying therapy. After a 4-week ezetimibe 10 mg/day run-in period, patients were randomized 2:1 to treatment with bempedoic acid 180 mg or placebo once daily added to ezetimibe 10 mg/day for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C. RESULTS: The study population comprised 269 patients (181 bempedoic acid, 88 placebo). Bempedoic acid added to background lipid-modifying therapy that included ezetimibe reduced LDL-C by 28.5% more than placebo (p < 0.001; -23.5% bempedoic acid, +5.0% placebo). Significant reductions in secondary endpoints, including non-high-density lipoprotein cholesterol (-23.6%), total cholesterol (-18.0%), apolipoprotein B (-19.3%), and high-sensitivity C-reactive protein (-31.0%), were observed with bempedoic acid vs. placebo (p < 0.001). Bempedoic acid was well tolerated; rates of treatment-emergent adverse events, muscle-related adverse events, and discontinuations were similar in the bempedoic acid and placebo treatment groups. CONCLUSIONS:Bempedoic acid may provide an oral therapeutic option complementary to ezetimibe in statin intolerant patients who require additional LDL-C lowering.
RCT Entities:
BACKGROUND AND AIMS: Patients with hyperlipidemia who are unable to tolerate optimal statin therapy are at increased cardiovascular risk due to ongoing elevations in low-density lipoprotein cholesterol (LDL-C). The objective of CLEAR Tranquility (NCT03001076) was to evaluate the efficacy and safety of bempedoic acid when added to background lipid-modifying therapy in patients with a history of statin intolerance who require additional LDL-C lowering. METHODS: This phase 3, multicenter, randomized, double-blind, placebo-controlled study enrolled patients with a history of statin intolerance and an LDL-C ≥100 mg/dL while on stable lipid-modifying therapy. After a 4-week ezetimibe 10 mg/day run-in period, patients were randomized 2:1 to treatment with bempedoic acid 180 mg or placebo once daily added to ezetimibe 10 mg/day for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C. RESULTS: The study population comprised 269 patients (181 bempedoic acid, 88 placebo). Bempedoic acid added to background lipid-modifying therapy that included ezetimibe reduced LDL-C by 28.5% more than placebo (p < 0.001; -23.5% bempedoic acid, +5.0% placebo). Significant reductions in secondary endpoints, including non-high-density lipoprotein cholesterol (-23.6%), total cholesterol (-18.0%), apolipoprotein B (-19.3%), and high-sensitivity C-reactive protein (-31.0%), were observed with bempedoic acid vs. placebo (p < 0.001). Bempedoic acid was well tolerated; rates of treatment-emergent adverse events, muscle-related adverse events, and discontinuations were similar in the bempedoic acid and placebo treatment groups. CONCLUSIONS:Bempedoic acid may provide an oral therapeutic option complementary to ezetimibe in statin intolerant patients who require additional LDL-C lowering.
Authors: Maciej Banach; Paweł Burchardt; Krzysztof Chlebus; Piotr Dobrowolski; Dariusz Dudek; Krzysztof Dyrbuś; Mariusz Gąsior; Piotr Jankowski; Jacek Jóźwiak; Longina Kłosiewicz-Latoszek; Irina Kowalska; Maciej Małecki; Aleksander Prejbisz; Michał Rakowski; Jacek Rysz; Bogdan Solnica; Dariusz Sitkiewicz; Grażyna Sygitowicz; Grażyna Sypniewska; Tomasz Tomasik; Adam Windak; Dorota Zozulińska-Ziółkiewicz; Barbara Cybulska Journal: Arch Med Sci Date: 2021-11-08 Impact factor: 3.318
Authors: Anne C Goldberg; Lawrence A Leiter; Erik S G Stroes; Seth J Baum; Jeffrey C Hanselman; LeAnne T Bloedon; Narendra D Lalwani; Pragna M Patel; Xin Zhao; P Barton Duell Journal: JAMA Date: 2019-11-12 Impact factor: 56.272