January 30, 2017Journal of the American College of Cardiology193 citationsOpen Access
View Full PaperSafety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab
Structured PICO
Does achieving very low LDL-C levels (<25 or <15 mg/dl) with alirocumab increase the risk of adverse events in patients on background lipid-lowering therapy?
P
Population
5,234 patients from 14 pooled trials in the ODYSSEY program (n=3,340 alirocumab, n=1,894 control) on background lipid-lowering therapy.
I
Intervention
Alirocumab added to background lipid-lowering therapy, specifically analyzing patients achieving 2 consecutive LDL-C values <25 mg/dl or <15 mg/dl.
C
Comparator
Control (placebo or ezetimibe) and alirocumab-treated patients not achieving LDL-C <25 mg/dl.
O
Outcome
Overall treatment-emergent adverse event rates, neurological events, neurocognitive events, and cataracts.safety
Achieving very low LDL-C levels (<25 or <15 mg/dl) with alirocumab is generally safe with no increase in overall or neurocognitive adverse events, though a potential signal for cataracts requires further observation.
Abstract
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. 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. 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). 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. 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)