Leslie Cho1, Ricardo Dent2, Erik S G Stroes3, Evan A Stein4, David Sullivan5, Andrea Ruzza2, Andrea Flower6, Ransi Somaratne2, Robert S Rosenson7. 1. Cleveland Clinic, 9500 Euclid Ave. Desk JB1, Cleveland, OH, 44195, USA. chol@ccf.org. 2. Clinical Development, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320-1799, USA. 3. Academic Medical Center of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam-Zuidoost, Amsterdam, The Netherlands. 4. Metabolic and Atherosclerosis Research Center, 5375 Medpace Way, Cincinnati, OH, 45227, USA. 5. Department of Clinical Biochemistry, Royal Prince Alfred Hospital, 50 Missenden Rd., Camperdown, NSW, 2050, Australia. 6. Global Statistical Science, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA, 91320-1799, USA. 7. Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl., New York, NY, 10029, USA.
Abstract
PURPOSE:Evolocumab reduced low-density lipoprotein cholesterol (LDL-C) in 12-week trials in statin-intolerant patients (GAUSS-1 and GAUSS-2); however, the persistence of efficacy during longer-term treatment is unknown. This subset analysis of the open-label extension studies (OSLER-1 and OSLER-2) aimed to evaluate the safety and efficacy of evolocumab up to 2 years in statin-intolerant patients. METHODS:Patients who completed GAUSS-1 and GAUSS-2 were enrolled in the OSLER studies and rerandomized 2:1 to evolocumab (140 mg biweekly or 420 mg monthly) plus standard of care (SOC) or SOC during year 1, and thereafter, evolocumab plus SOC. RESULTS:A total of 382 statin-intolerant patients who completed the GAUSS-1 and GAUSS-2 parent studies were enrolled and rerandomized into the OSLER studies. After year 1, 246 (98%) patients randomized to evolocumab plus SOC and 124 (95%) on SOC during year 1 remained in the OSLER studies; after year 2, 364 (95%) remained on study. Mean parent study baseline LDL-C concentration was 4.97-5.02 mmol/L (192-194 mg/dL). The median percentage reduction from baseline in LDL-C was 13% for SOC and 57% for evolocumab plus SOC at year 1, and 59% for evolocumab plus SOC at year 2. The patient incidence of muscle-related adverse events during year 1 in the SOC and evolocumab plus SOC groups was 16% and 14%, respectively, and 11% for evolocumab plus SOC at year 2. No patient discontinued the study due to adverse events. CONCLUSION:Evolocumab plus SOC was persistently safe, tolerable, and efficacious for up to 2 years in statin-intolerant patients.
RCT Entities:
PURPOSE:Evolocumab reduced low-density lipoprotein cholesterol (LDL-C) in 12-week trials in statin-intolerant patients (GAUSS-1 and GAUSS-2); however, the persistence of efficacy during longer-term treatment is unknown. This subset analysis of the open-label extension studies (OSLER-1 and OSLER-2) aimed to evaluate the safety and efficacy of evolocumab up to 2 years in statin-intolerant patients. METHODS:Patients who completed GAUSS-1 and GAUSS-2 were enrolled in the OSLER studies and rerandomized 2:1 to evolocumab (140 mg biweekly or 420 mg monthly) plus standard of care (SOC) or SOC during year 1, and thereafter, evolocumab plus SOC. RESULTS: A total of 382 statin-intolerant patients who completed the GAUSS-1 and GAUSS-2 parent studies were enrolled and rerandomized into the OSLER studies. After year 1, 246 (98%) patients randomized to evolocumab plus SOC and 124 (95%) on SOC during year 1 remained in the OSLER studies; after year 2, 364 (95%) remained on study. Mean parent study baseline LDL-C concentration was 4.97-5.02 mmol/L (192-194 mg/dL). The median percentage reduction from baseline in LDL-C was 13% for SOC and 57% for evolocumab plus SOC at year 1, and 59% for evolocumab plus SOC at year 2. The patient incidence of muscle-related adverse events during year 1 in the SOC and evolocumab plus SOC groups was 16% and 14%, respectively, and 11% for evolocumab plus SOC at year 2. No patient discontinued the study due to adverse events. CONCLUSION:Evolocumab plus SOC was persistently safe, tolerable, and efficacious for up to 2 years in statin-intolerant patients.