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Livelli molto bassi di colesterolo in soggetti trattati con alirocumab: sono sicuri?

In questa analisi su oltre 800 pazienti trattati con alirocumab per un periodo medio di 18 mesi, che hanno riportato una riduzione farmacologica dei livelli di c-LDL al di sotto di 25 mg/dL, l'incidenza totale di eventi avversi emersi a seguito del trattamento era simile tra gli esposti e i non esposti, così come all'interno dei gruppi trattati con alirocumab in base ai livelli di colesterolo LDL raggiunti. In particolare, i disturbi neurologici e neurocognitivi erano simili tra i 3 gruppi. La percentuale di cataratta era più alta nei pazienti con valori di c-LDL<25 mg/dL vs =25 mg/dL; tuttavia, non è stata osservata alcuna differenza nell'incidenza di cataratta tra coloro che assumevano alirocumab e i gruppi controllo.

Safety of Very Low Low-Density Lipoprotein Cholesterol Levels With Alirocumab: Pooled Data From Randomized Trials

Robinson JG, Rosenson RS, Farnier M, Chaudhari U, Sasiela WJ, Merlet L, Miller K, Kastelein JJ

J Am Coll Cardiol 2017; 69:471-482

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.

J Am Coll Cardiol 2017; 69:471-482