Patrick M Moriarty1, Paul D Thompson2, Christopher P Cannon3, John R Guyton4, Jean Bergeron5, Franklin J Zieve6, Eric Bruckert7, Terry A Jacobson8, Marie T Baccara-Dinet9, Jian Zhao10, Stephen Donahue11, Shazia Ali11, Garen Manvelian11, Robert Pordy11. 1. Division of Clinical Pharmacology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA. Electronic address: pmoriart@kumc.edu. 2. Hartford Hospital, Hartford, CT, USA. 3. Baim Institute for Clinical Research, Boston, MA, USA. 4. Duke University Medical Center, Durham, NC, USA. 5. Lipid Clinic, Centre Hospitalier Universitaire de Quebec, Laval University, Quebec, Canada. 6. McGuire VA Medical Center, Richmond, VA, USA. 7. Groupe Hospitalier Pitié-Salpêtrière (Assistance Publique-Hôpitaux de Paris), Paris, France. 8. Department of Medicine, Emory University, Atlanta, GA, USA. 9. Sanofi, Montpellier, France. 10. Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA. 11. Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Abstract
BACKGROUND: The 24-week randomized, double-blind ODYSSEY ALTERNATIVE trial (NCT01709513) demonstrated significant low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 inhibitor alirocumab vs ezetimibe in statin-intolerant patients, with significantly fewer skeletal muscle events (SMEs; 32.5%) vs atorvastatin (46.0%; hazard ratio: 0.61, 95% confidence interval: 0.38 to 0.99, P = .042). OBJECTIVE: ALTERNATIVE participants could enter an open-label treatment period (OLTP) for assessment of long-term safety. METHODS:Two hundred and eighty one patients entered theOLTP; 93.7%, 84.0%, and 92.9% of patients who received atorvastatin, ezetimibe, and alirocumab, respectively, during double-blind treatment, including 216 patients (76.9%) who completed double-blind treatment, as well as patients who either prematurely discontinued treatment due to SME (n = 51 [18.1%]) or other reasons (n = 14 [5.0%]) but completed week 24 assessments. All patients in the OLTP received alirocumab (75 or 150 mg every 2 weeks based on investigator decision) for ∼3 years or until commercial availability, whichever came first. RESULTS:SMEs were reported by 38.4% of patients in the OLTP. Safety results from the OLTP were similar to those of the alirocumab group in the double-blind period, except for a lower rate of discontinuations due to SMEs observed with alirocumab in the OLTP (3.2% vs 15.9% in the double-blind period). At OLTP week 8, mean LDL-C reduction from baseline (=week 0 of double-blind period) was 52.0%, with reductions sustained through to the end-of-treatment visits (55.4% and 53.7% reduction at weeks 100 and 148, respectively). CONCLUSIONS: In this population of statin-intolerant patients, alirocumab was well tolerated and produced durable LDL-C reductions over 3 years.
RCT Entities:
BACKGROUND: The 24-week randomized, double-blind ODYSSEY ALTERNATIVE trial (NCT01709513) demonstrated significant low-density lipoprotein cholesterol (LDL-C) reductions with the PCSK9 inhibitor alirocumab vs ezetimibe in statin-intolerant patients, with significantly fewer skeletal muscle events (SMEs; 32.5%) vs atorvastatin (46.0%; hazard ratio: 0.61, 95% confidence interval: 0.38 to 0.99, P = .042). OBJECTIVE: ALTERNATIVE participants could enter an open-label treatment period (OLTP) for assessment of long-term safety. METHODS: Two hundred and eighty one patients entered the OLTP; 93.7%, 84.0%, and 92.9% of patients who received atorvastatin, ezetimibe, and alirocumab, respectively, during double-blind treatment, including 216 patients (76.9%) who completed double-blind treatment, as well as patients who either prematurely discontinued treatment due to SME (n = 51 [18.1%]) or other reasons (n = 14 [5.0%]) but completed week 24 assessments. All patients in the OLTP received alirocumab (75 or 150 mg every 2 weeks based on investigator decision) for ∼3 years or until commercial availability, whichever came first. RESULTS:SMEs were reported by 38.4% of patients in the OLTP. Safety results from the OLTP were similar to those of the alirocumab group in the double-blind period, except for a lower rate of discontinuations due to SMEs observed with alirocumab in the OLTP (3.2% vs 15.9% in the double-blind period). At OLTP week 8, mean LDL-C reduction from baseline (=week 0 of double-blind period) was 52.0%, with reductions sustained through to the end-of-treatment visits (55.4% and 53.7% reduction at weeks 100 and 148, respectively). CONCLUSIONS: In this population of statin-intolerant patients, alirocumab was well tolerated and produced durable LDL-C reductions over 3 years.
Authors: Emmanuelar O Igweonu-Nwakile; Safina Ali; Salomi Paul; Shreyas Yakkali; Sneha Teresa Selvin; Sonu Thomas; Viktoriya Bikeyeva; Ahmed Abdullah; Aleksandra Radivojevic; Anas A Abu Jad; Anvesh Ravanavena; Chetna Ravindra; Prachi Balani Journal: Cureus Date: 2022-09-13