Jennifer G Robinson1, Robert S Rosenson2, Michel Farnier3, Umesh Chaudhari4, William J Sasiela5, Laurence Merlet6, Kathryn Miller7, John J P Kastelein8. 1. University of Iowa, Iowa City, Iowa. Electronic address: jennifer-g-robinson@uiowa.edu. 2. Icahn School of Medicine at Mount Sinai, New York, New York. 3. Point Médical, Dijon, France. 4. Sanofi, Bridgewater, New Jersey. 5. Regeneron Pharmaceuticals, Inc., Tarrytown, New York. 6. Sanofi, Chilly-Mazarin, France. 7. Regeneron Pharmaceuticals, Inc., Basking Ridge, New Jersey. 8. Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
Abstract
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies can reduce low-density lipoprotein cholesterol (LDL-C) to very low levels when added to background lipid-lowering therapy. OBJECTIVES: The safety of alirocumab was evaluated in patients with at least 2 consecutive LDL-C values <25 or <15 mg/dl in the ODYSSEY program, with follow-up as long as 104 weeks. METHODS: Pooled data from 14 trials were analyzed (double-blind treatment 8 to 104 weeks; n = 3,340 alirocumab, n = 1,894 control [placebo or ezetimibe]; representing 4,029 [alirocumab] and 2,114 [control] double-blind patient-years' exposure). RESULTS: In alirocumab-treated patients, 839 (25.1%) achieved 2 consecutive LDL-C values <25 mg/dl, and 314 (9.4%) achieved <15 mg/dl. Baseline LDL-C was lower (mean 100.3 vs. 134.3 mg/dl) in patients with LDL-C <25 versus ≥25 mg/dl. Similar rates of adverse events occurred in patients achieving LDL-C <25 and <15 mg/dl (72.7% and 71.7%, respectively), compared with 76.6% in those who did not achieve LDL-C <25 mg/dl. Neurological and neurocognitive events were similar among the 3 groups. In a propensity score analysis, the rate of cataracts was higher in patients with LDL-C <25 mg/dl (2.6%) versus ≥25 mg/dl (0.8%; hazard ratio: 3.40; 95% confidence interval: 1.58 to 7.35). However, no difference in cataract incidence was observed between pooled alirocumab and control groups. CONCLUSIONS:LDL-C levels <25 or <15 mg/dl on alirocumab were not associated with an increase in overall treatment-emergent adverse event rates or neurocognitive events, although cataract incidence appeared to be increased in the group achieving LDL-C levels <25 mg/dl. (Pooled analyses of already reported trials; NCT01288443, NCT01288469, NCT01266876, NCT01812707, NCT01507831, NCT01617655, NCT01623115, NCT01709500, NCT01644175, NCT01644188, NCT01730040, NCT01730053, NCT01644474, and NCT01709513).
RCT Entities:
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies can reduce low-density lipoprotein cholesterol (LDL-C) to very low levels when added to background lipid-lowering therapy. OBJECTIVES: The safety of alirocumab was evaluated in patients with at least 2 consecutive LDL-C values <25 or <15 mg/dl in the ODYSSEY program, with follow-up as long as 104 weeks. METHODS: Pooled data from 14 trials were analyzed (double-blind treatment 8 to 104 weeks; n = 3,340 alirocumab, n = 1,894 control [placebo or ezetimibe]; representing 4,029 [alirocumab] and 2,114 [control] double-blind patient-years' exposure). RESULTS: In alirocumab-treated patients, 839 (25.1%) achieved 2 consecutive LDL-C values <25 mg/dl, and 314 (9.4%) achieved <15 mg/dl. Baseline LDL-C was lower (mean 100.3 vs. 134.3 mg/dl) in patients with LDL-C <25 versus ≥25 mg/dl. Similar rates of adverse events occurred in patients achieving LDL-C <25 and <15 mg/dl (72.7% and 71.7%, respectively), compared with 76.6% in those who did not achieve LDL-C <25 mg/dl. Neurological and neurocognitive events were similar among the 3 groups. In a propensity score analysis, the rate of cataracts was higher in patients with LDL-C <25 mg/dl (2.6%) versus ≥25 mg/dl (0.8%; hazard ratio: 3.40; 95% confidence interval: 1.58 to 7.35). However, no difference in cataract incidence was observed between pooled alirocumab and control groups. CONCLUSIONS: LDL-C levels <25 or <15 mg/dl on alirocumab were not associated with an increase in overall treatment-emergent adverse event rates or neurocognitive events, although cataract incidence appeared to be increased in the group achieving LDL-C levels <25 mg/dl. (Pooled analyses of already reported trials; NCT01288443, NCT01288469, NCT01266876, NCT01812707, NCT01507831, NCT01617655, NCT01623115, NCT01709500, NCT01644175, NCT01644188, NCT01730040, NCT01730053, NCT01644474, and NCT01709513).
Authors: Matthew T Mefford; Robert S Rosenson; Mary Cushman; Michael E Farkouh; Leslie A McClure; Virginia G Wadley; Marguerite R Irvin; Vera Bittner; Monika M Safford; Ransi Somaratne; Keri L Monda; Paul Muntner; Emily B Levitan Journal: Circulation Date: 2017-11-16 Impact factor: 29.690
Authors: Robert P Giugliano; Stephen D Wiviott; Michael A Blazing; Gaetano M De Ferrari; Jeong-Gun Park; Sabina A Murphy; Jennifer A White; Andrew M Tershakovec; Christopher P Cannon; Eugene Braunwald Journal: JAMA Cardiol Date: 2017-05-01 Impact factor: 14.676
Authors: Peter E Penson; D Leann Long; George Howard; Peter P Toth; Paul Muntner; Virginia J Howard; Monica M Safford; Steven R Jones; Seth S Martin; Mohsen Mazidi; Alberico L Catapano; Maciej Banach Journal: Eur Heart J Date: 2018-10-21 Impact factor: 29.983
Authors: Christopher P Cannon; Irfan Khan; Alexa C Klimchak; Matthew R Reynolds; Robert J Sanchez; William J Sasiela Journal: JAMA Cardiol Date: 2017-09-01 Impact factor: 14.676