OBJECTIVES: A network meta-analysis (NMA) was conducted to compare the efficacy (LDL-C lowering) between different classes of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, small interfering RNA (siRNA) vs. PCSK9i monoclonal antibodies (mAb) (inclisiran vs. evolocumab, alirocumab, and tafolecimab), among Asian patients with increased cardiovascular risk having elevated low-density lipoprotein cholesterol (LDL-C) despite taking maximally tolerated dose statins (MTDS).

METHODS: A systematic review was conducted using OvidSP (MEDLINE and Embase), Cochrane (Wiley), Pubmed, and Web of Science databases to identify published randomized controlled trials through January 2023 and supplemented with tafolecimab trial publications (domestic PCSK9i in China). The primary outcome was the percentage change in LDL-C from baseline to week 24 (or closest available time point). Results are presented for two scenarios including studies with ASCVD patients on moderate intensity statins with pooled PCSK9i mAbs (scenario 1: pooled evolocumab and alirocumab together; scenario 2: pooled evolocumab, alirocumab, and tafolecimab). A random-effects Bayesian NMA was performed to estimate the mean differences (MD) and 95% credible intervals (CrI) for the included therapies.

RESULTS: 9 studies were included in the analysis [Inclisiran (N=2), Evolocumab (N=2), Alirocumab (N=2), and Tafolecimab (N=3)]. Inclisiran showed superior efficacy over placebo in reducing LDL-C from baseline at week 24 (MD: -63.06% [95% CI: -68.91, -57.34]). In both the scenarios, inclisiran demonstrated a numerical improvement, although the observed benefits were not statistically significant vs pooled PCSK9i mAb (vs evolocumab + alirocumab, MD: -0.43% [95% CrI: -9.89, 8.82]; vs tafolecimab, MD: -3.15% [95% CrI: -12.49, 5.98]; and vs evolocumab + alirocumab + tafolecimab, MD: -2.5% [95% CrI: -11.26, 6.22]).

CONCLUSIONS: This NMA ascertains that in Asian patients with hypercholesterolemia, at increased CV risk and at MTDS, inclisiran (siRNA) with twice-yearly dosing is expected to show clinically meaningful LDL-C reductions comparable to PCSK9i mAb.