PCSK9 Inhibitor Deemed Safe for Long-Term Use

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab is safe and effective for lowering low-density lipoprotein (LDL) cholesterol levels in the long-term compared with ezetimibe, according to a recent study. Alirocumab was well tolerated for up to 2 years.

Previous studies have shown that alirocumab use is associated with substantially lower LDL levels. However, less is known about the safety and efficacy of long term use of alirocumab.
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In the COMBO II trial, the researchers assigned 720 patients receiving a maximally tolerated statin dose to receive either 75/150 mg alirocumab every 2 weeks (n=454) or 10 mg/ ezetimibe daily (n=231) for 2 years. A prespecified first analysis was reported after 1 year.

Overall mean adherence in both treatment groups was over 97% during both the first and second years. Results indicated that the alirocumab group experienced a 49% decrease in LDL levels vs a 17% decrease in the ezetimibe group. LDL levels below 70 mg/dl were reported in 73% of patients in the alirocumab group compared with 40% in the ezetimibe group.

The researchers noted that overall safety was similar in both groups at 2 years and during the first vs the second year. In the first year, 2.5% of patients on alirocumab reported local injection-site reactions compared with 0.8% in the ezetimibe group. However, during the second year, local injection-site reactions occurred in 0.2% on alirocumab vs 0.5% on ezetimibe, demonstrating early occurrence during prolonged exposure to alirocumab.

Ultimately, 28% of patients on alirocumab achieved 2 consecutive calculated LDL values below 25 mg/dl compared with 0.4% of patients on ezetimibe. Additionally, 6 alirocumab-treated patients (1.3%) demonstrated persistent anti-drug antibody responses compared with 1 (0.4%) ezetimibe-treated patient. Neutralizing antibodies were present in 7 (1.5%) patients on alirocumab vs 0 on ezetimibe, mostly at isolated time points.

“Alirocumab sustained substantial LDL-C reductions and was well tolerated up to 2 years in the COMBO II trial,” the researchers concluded.

—Christina Vogt

Reference:

Shahawy ME, Cannon CP, Blom DJ, et al. Efficacy and safety of alirocumab versus ezetimibe over 2 years (from ODYSSEY COMBO II). Am J Cardiol. 2017;120(6):931-939.  http://dx.doi.org/10.1016/j.amjcard.2017.06.023.