TY - JOUR
T1 - Efficacy and safety of inclisiran in patients with cerebrovascular disease
T2 - ORION-9, ORION-10, and ORION-11
AU - Koenig, Wolfgang
AU - Ray, Kausik K.
AU - Landmesser, Ulf
AU - Leiter, Lawrence A.
AU - Schwartz, Gregory G.
AU - Wright, R. Scott
AU - Conde, Lorena Garcia
AU - Han, Jackie
AU - Raal, Frederick J.
N1 - Publisher Copyright:
© 2023
PY - 2023/6
Y1 - 2023/6
N2 - Patients with cerebrovascular disease (CeVD) have been shown to benefit from lipid-lowering therapies, but guideline-recommended levels of low-density lipoprotein cholesterol (LDL-C) are often not attained with statin treatment alone. The ORION-9, ORION-10, and ORION-11 trials evaluated the efficacy and safety of inclisiran in 3660 primary and secondary prevention patients with hyperlipidemia despite maximum tolerated statin treatment. This pooled post hoc analysis comprised 202 randomized patients from those trials with established CeVD who had received either 284 mg inclisiran (equivalent to 300 mg inclisiran sodium, n = 110) or placebo (n = 92) on Days 1, 90, and 6-monthly thereafter up to Day 540. At baseline, mean (SD) LDL-C was 108.4 (34.3) mg/dL and 110.5 (35.3) mg/dL in inclisiran and placebo arms, respectively. Inclisiran produced a mean (95% CI) placebo-corrected percentage change in LDL-C from baseline to Day 510 of –55.2 (–64.5 to –45.9; p < 0.0001); the corresponding time-adjusted percentage change from baseline after Day 90 and up to Day 540 was –55.2 (–62.4 to –47.9; p < 0.0001). Treatment-emergent adverse events (TEAEs) and TEAEs at the injection site, mostly mild, were more frequent with inclisiran versus placebo (82.7% vs 70.7% and 3.6% vs 0%, respectively). In patients with CeVD, twice-yearly dosing with inclisiran (after the initial and 3-month doses) in combination with maximally tolerated statins provided effective and consistent LDL-C reductions and was well tolerated.
AB - Patients with cerebrovascular disease (CeVD) have been shown to benefit from lipid-lowering therapies, but guideline-recommended levels of low-density lipoprotein cholesterol (LDL-C) are often not attained with statin treatment alone. The ORION-9, ORION-10, and ORION-11 trials evaluated the efficacy and safety of inclisiran in 3660 primary and secondary prevention patients with hyperlipidemia despite maximum tolerated statin treatment. This pooled post hoc analysis comprised 202 randomized patients from those trials with established CeVD who had received either 284 mg inclisiran (equivalent to 300 mg inclisiran sodium, n = 110) or placebo (n = 92) on Days 1, 90, and 6-monthly thereafter up to Day 540. At baseline, mean (SD) LDL-C was 108.4 (34.3) mg/dL and 110.5 (35.3) mg/dL in inclisiran and placebo arms, respectively. Inclisiran produced a mean (95% CI) placebo-corrected percentage change in LDL-C from baseline to Day 510 of –55.2 (–64.5 to –45.9; p < 0.0001); the corresponding time-adjusted percentage change from baseline after Day 90 and up to Day 540 was –55.2 (–62.4 to –47.9; p < 0.0001). Treatment-emergent adverse events (TEAEs) and TEAEs at the injection site, mostly mild, were more frequent with inclisiran versus placebo (82.7% vs 70.7% and 3.6% vs 0%, respectively). In patients with CeVD, twice-yearly dosing with inclisiran (after the initial and 3-month doses) in combination with maximally tolerated statins provided effective and consistent LDL-C reductions and was well tolerated.
KW - Cerebrovascular disease
KW - Inclisiran
KW - LDL-cholesterol
KW - Safety
KW - siRNA
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U2 - 10.1016/j.ajpc.2023.100503
DO - 10.1016/j.ajpc.2023.100503
M3 - Article
AN - SCOPUS:85162333511
SN - 2666-6677
VL - 14
JO - American Journal of Preventive Cardiology
JF - American Journal of Preventive Cardiology
M1 - 100503
ER -